AzTrials
AzTrials

Diabetic Macular EdemaPhase 3RHINENCT03622593

A Study to Evaluate the Efficacy and Safety of Faricimab (RO6867461) in Participants With Diabetic Macular Edema

A Phase 3 study testing Aflibercept and Faricimab in people with Diabetic Macular Edema, run by Hoffmann-La Roche at 188 sites in 24 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study will evaluate the efficacy, safety, and pharmacokinetics of faricimab administered at 8-week intervals or as specified in the protocol following treatment initiation, compared with aflibercept once every 8 weeks (Q8W), in participants with diabetic macular edema (DME). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Diabetic Macular Edema
What is being tested?
Aflibercept and Faricimab
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
951 participants
Where
188 sitesin 24 countries
Study dates
9 Oct 2018to 31 May 2023
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Documented diagnosis of diabetes mellitus (Type 1 or Type 2)
  • Hemoglobin A1c (HbA1c) of less than or equal to (≤)10% within 2 months prior to Day 1
  • Macular thickening secondary to diabetic macular edema (DME) involving the center of the fovea
  • Decreased visual acuity attributable primarily to DME
  • Ability and willingness to undertake all scheduled visits and assessments
  • For women of childbearing potential: agreement to remain abstinent or use acceptable contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 3 months after the final dose of study treatment

Who cannot join

  • Currently untreated diabetes mellitus or previously untreated patients who initiated oral or injectable anti-diabetic medication within 3 months prior to Day 1
  • Uncontrolled blood pressure, defined as a systolic value greater than (>)180 millimeters of mercury (mmHg) and/or a diastolic value >100 mmHg while a patient is at rest
  • Currently pregnant or breastfeeding, or intend to become pregnant during the study
  • Treatment with panretinal photocoagulation or macular laser within 3 months prior to Day 1 to the study eye
  • Any intraocular or periocular corticosteroid treatment within 6 months prior to Day 1 to the study eye
  • Prior administration of IVT faricimab in either eye
Show all 10Show fewer
  • Active intraocular or periocular infection or active intraocular inflammation in the study eye
  • Any current or history of ocular disease other than DME that may confound assessment of the macula or affect central vision in the study eye
  • Any current ocular condition which, in the opinion of the investigator, is currently causing or could be expected to contribute to irreversible vision loss due to a cause other than DME in the study eye
  • Other protocol-specified inclusion/exclusion criteria may apply

Trial locations and contacts

188 sites in 24 countries.

188 sites in 24 countries

United States50 sites
  • Southeast Retina Center

    Augusta, Georgia, 30909

  • University of Colorado

    Aurora, Colorado, 80045

  • Austin Retina Associates

    Austin, Texas, 78705

  • California Retina Consultants

    Bakersfield, California, 93309

  • Retina Specialists

    Baltimore, Maryland, 21204

  • Retina Consultants of Texas

    Bellaire, Texas, 77401

  • Retina-Vitreous Associates Medical Group

    Beverly Hills, California, 90211

  • Envision Ocular, LLC

    Bloomfield, New Jersey, 07003

  • Tufts Medical Center

    Boston, Massachusetts, 02111

  • Univ of Virginia Ophthalmology

    Charlottesville, Virginia, 22903

  • Southeastern Retina Associates Chattanooga

    Chattanooga, Tennessee, 37421

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Retina Consultants of Southern

    Colorado Springs, Colorado, 80909

  • The Retina Partners

    Encino, California, 91436

  • Retina Group of Florida

    Fort Lauderdale, Florida, 33308

  • National Ophthalmic Research Institute

    Fort Myers, Florida, 33912

  • Retina Consultants of Orange County

    Fullerton, California, 92835

  • Associated Retinal Consultants

    Grand Rapids, Michigan, 49546

  • Vitreo-Retinal Associates

    Grand Rapids, Michigan, 49546

  • Retina Consultants Of Carolina

    Greenville, South Carolina, 29605

  • Long Is. Vitreoretinal Consult

    Hauppauge, New York, 11788

  • Southeastern Retina Associates

    Knoxville, Tennessee, 37922

  • Charleston Neuroscience Inst

    Ladson, South Carolina, 29456

  • Retina Consultants of Nevada

    Las Vegas, Nevada, 89144

  • Florida Eye Associates

    Melbourne, Florida, 32901

  • Northern California Retina Vitreous Associates

    Mountain View, California, 94040

  • Tennessee Retina PC

    Nashville, Tennessee, 37203

  • New York University

    New York, New York, 10017

  • University Retina and Macula Associates, PC

    Oak Forest, Illinois, 60452

  • Ophthalmic Cons of Long Island

    Oceanside, New York, 11572

  • Bascom Palmer Eye Institute

    Palm Beach Gardens, Florida, 33418

  • Mid Atlantic Retina - Wills Eye Hospital

    Philadelphia, Pennsylvania, 19107

  • Associated Retina Consultants

    Phoenix, Arizona, 85020

  • Retinal Research Institute, LLC

    Phoenix, Arizona, 85053

  • Fort Lauderdale Eye Institute

    Plantation, Florida, 33324

  • Retina Institute of Virginia

    Richmond, Virginia, 23235

  • Retina Assoc of Western NY

    Rochester, New York, 14620

  • University of Rochester Flaum Eye Institute

    Rochester, New York, 14642

  • Retinal Consultants Med Group

    Sacramento, California, 95825

  • California Retina Consultants

    Santa Barbara, California, 93103

  • California Retina Consultants

    Santa Maria, California, 93454

  • Pacific Northwest Retina

    Silverdale, Washington, 98383

  • The Retina Consultants

    Slingerlands, New York, 12159

  • Retina Center of Texas

    Southlake, Texas, 76092

  • Northwest Arkansas Retina Associates

    Springdale, Arkansas, 72764

  • Prairie Retina Center

    Springfield, Illinois, 62704

  • Retina Vitreous Assoc of FL

    St. Petersburg, Florida, 33711

  • Bay Area Retina Associates

    Walnut Creek, California, 94598

  • Retina Group of New England

    Waterford, Connecticut, 06385

  • Palmetto Retina Center

    West Columbia, South Carolina, 29169

Other trials in United States

United Kingdom18 sites
  • Barnet Hospital

    Barnet, EN5 3DJ

  • Bradford Royal Infirmary

    Bradford, BD9 6RJ

  • University Hospitals Bristol NHS Foundation Trust, Bristol Eye Hospital

    Bristol, BS1 2LX

  • Belfast Health and Social Care Trust, ROYAL VICTORIA HOSPITAL

    Bristol, BT12 6BA

  • East Kent Hospitals University NHS Foundation Trust

    Canterbury, CT1 3NG

  • Frimley Park Hospital

    Frimley, GU16 7UJ

  • Gloucestershire Hospitals NHS Foundation Trust

    Gloucester, GL1 3NN

  • James Paget University Hospitals NHS Foundation Trust

    Great Yarmouth, NR31 6LA

  • St James University Hospital

    Leeds, LS9 7TF

  • Royal Liverpool University Hospital

    Liverpool, L7 8XP

  • Moorfields Eye Hospital NHS Foundation Trust

    London, EC1V 2PD

  • Royal Free Hospital

    London, NW3 2QS

  • Kings College Hospital

    London, SE5 9RS

  • Manchester Royal Eye Hospital

    Manchester, M13 9WL

  • Royal Victoria Infirmary

    Newcastle upon Tyne, NE1 4LP

  • University Hospital Southampton NHS Foundation Trust

    Southampton, SO16 6YD

  • Sunderland Eye Infirmary

    Sunderland, SR2 9HP

  • Hillingdon Hospital

    Uxbridge, UB8 3NN

Other trials in United Kingdom

China15 sites
  • Beijing Friendship Hospital

    Beijing, 100050

  • Beijing Tongren Hospital

    Beijing, 100730

  • Peking Union Medical College Hospital

    Beijing, 100730

  • The Second Hospital of Jilin University

    Changchun, 130041

  • West China Hospital, Sichuan University

    Chengdu, 610041

  • Southwest Hospital , Third Military Medical University

    Chongqing, 400014

  • Army Medical Center of PLA(Daping Hospital)

    Chongqing, 400042

  • Zhongshan Ophthalmic Center, Sun Yat-sen University

    Guangzhou, 510060

  • The Affiliated Eye Hospital of Nanjing Medical University

    Nanjing, 210029

  • Shanghai Tenth People's Hospital

    Shanghai, 200072

  • Shanghai First People's Hospital

    Shanghai, 200080

  • Tianjin Eye Hospital

    Tianjin, 300050

  • Tianjin Medical University Eye Hospital

    Tianjin, 300070

  • Eye Hospital, Wenzhou Medical University

    Wenzhou, 325027

  • Wuxi No.2 People's Hospital

    Wuxi, 214000

Other trials in China

Canada10 sites
  • Institut De L'Oeil Des Laurentides

    Boisbriand, Quebec, J7H 1S6

  • Calgary Retina Consultants

    Calgary, Alberta, T2J 0C8

  • QEII - HSC Department of Ophthalmology

    Halifax, Nova Scotia, B3H 2Y9

  • Ivey Eye Institute

    London, Ontario, N6A 4V2

  • Hôpital Maisonneuve - Rosemont

    Montreal, Quebec, H1T 2M4

  • University of Ottawa Eye Institute

    Ottawa, Ontario, K1H 8L6

  • Toronto Retina Institute

    Toronto, Ontario, M3C 0G9

  • Unity Health Toronto

    Toronto, Ontario, M5C 2T2

  • University Health Network Toronto Western Hospital

    Toronto, Ontario, M5T 2S8

  • University of British Columbia - Vancouver Coastal Health Authority

    Vancouver, British Columbia, V5Z 1M9

Other trials in Canada

Brazil9 sites
  • Hospital de Olhos de Aparecida - HOA

    Aparecida de Goiânia, Goiás, 74980-010

  • Botelho Hospital da Visao

    Blumenau, Santa Catarina, 89052-504

  • Centro Brasileiro de Cirurgia

    Goiânia, Goiás, 74210-010

  • Hospital das Clinicas - UFRGS

    Porto Alegre, Rio Grande do Sul, 90035-003

  • Faculdade de Medicina do ABC - FMABC

    Santo André, São Paulo, 09060-650

  • Universidade Federal de Sao Paulo - UNIFESP*X

    São Paulo, São Paulo, 04023-062

  • CEMAPE - Centro Médico

    São Paulo, São Paulo, 04084-002

  • Hospital das Clinicas - FMUSP

    São Paulo, São Paulo, 05403-000

  • Hosp de Olhos de Sorocaba

    Sorocaba, São Paulo, 18031-060

Other trials in Brazil

Spain9 sites
  • Hospital dos de maig

    Barcelona, 08025

  • Oftalvist Valencia

    Burjassot, Valencia, 46100

  • Hospital Universitario de Bellvitge

    L'Hospitalet de Llobregat, Barcelona, 08907

  • Clinica Baviera

    Madrid, 28046

  • Instituto Oftalmologico Fernandez Vega

    Oviedo, Principality of Asturias, 33012

  • Complejo Hospitalario de Navarra

    Pamplona, Navarre, 31008

  • Hospital General de Catalunya

    Sant Cugat del Vallès, Barcelona, 08195

  • Fisabio-Ofalmologia Medica

    Valencia, 46015

  • Hospital Universitario Rio Hortega

    Valladolid, 47012

Other trials in Spain

Poland8 sites
  • OFTALMIKA Sp. z o.o

    Bydgoszcz, 85-631

  • Specjalistyczny O?rodek Okulistyczny Oculomedica

    Bydgoszcz, 85-870

  • Optimum Profesorskie Centrum Okulistyki

    Gdansk, 80-809

  • Niepubliczny Zaklad Opieki Zdrowotnej PRYZMAT-OKULISTYKA

    Gliwice, 44-100

  • SP ZOZ Szpital Uniwersytecki w Krakowie Oddzia? Kliniczny Okulistyki i Onkologii Okulistycznej

    Krakow, 31-501

  • Osrodek Chirurgii Oka prof. Zagorskiego Rzeszow

    Rzeszów, 35-017

  • Caminomed

    Tarnowskie Góry, 42-600

  • Centrum Zdrowia MDM

    Warsaw, 00-631

Other trials in Poland

Australia7 sites
  • Centre For Eye Research Australia

    East Melbourne, Victoria, 3002

  • The Lions Eye Institute

    Nedlands, Western Australia, 6009

  • Retina Specialists Victoria

    Rowville, Victoria, 3178

  • Strathfield Retina Clinic

    Strathfield, New South Wales, 2135

  • Sydney Eye Hospital

    Sydney, New South Wales, 2000

  • Sydney Retina Clinic and Day Surgery

    Sydney, New South Wales, 2000

  • Sydney West Retina

    Westmead, New South Wales, 2145

Other trials in Australia

Germany7 sites
  • Universitätsklinikum Carl Gustav Carus, Klinik und Poliklinik für Augenheilkunde

    Dresden, 01307

  • Universitätsklinikum Freiburg, Klinik für Augenheilkunde

    Freiburg im Breisgau, 79106

  • Universitätsklinikum des Saarlandes

    Homburg/Saar, 66424

  • Universitätsklinikum Magdeburg A.ö.R., Universitätsaugenklinik

    Magdeburg, 39120

  • LMU Klinikum der Universität, Augenklinik

    München, 80336

  • Klinikum rechts der Isar der TU München

    München, 81675

  • Universitätsklinikum Würzburg, Augenklinik und Poliklinik

    Würzburg, 97080

Other trials in Germany

Argentina6 sites
  • Organizacion Medica de Investigacion

    Buenos Aires, C1015ABO

  • Fundacion Zambrano

    CABA, 1023

  • Oftalmos

    Capital Federal, C1120AAN

  • Oftar

    Mendoza, M5500GGK

  • Centro Oftalmólogos Especialistas

    Rosario, S2000ANJ

  • Grupo Laser Vision

    Rosario, S2000DLA

Other trials in Argentina

Czechia5 sites
  • FN Hradec Králové, O?ní klinika

    Hradec Králové, 500 05

  • Faculty Hospital Ostrava

    Ostrava, 708 52

  • Faculty Hospital Kralovske Vinohrady

    Prague, 100 34

  • AXON Clinical

    Prague

  • Nemocnice Sokolov

    Sokolov, 356 01

Other trials in Czechia

Italy5 sites
  • Azienda Ospedaliero-Universitaria Careggi

    Florence, Tuscany, 50134

  • Ospedale Classificato Equiparato Sacro Cuore Don Calabria

    Negrar, Veneto, 37024

  • Nuovo Ospedale S. Chiara - A.O.U.P Presidio Ospedaliero di Cisanello

    Pisa, Tuscany, 56124

  • Fondazione Ptv Policlinico Tor Vergata Di Roma

    Rome, Lazio, 00133

  • A.O. Universitaria S. Maria Della Misericordia Di Udine

    Udine, Veneto, 33100

Other trials in Italy

South Korea5 sites
  • Seoul National University Bundang Hospital

    Gyeonggi-do, 13620

  • Kyung Hee University Hospital

    Seoul, 02447

  • Seoul National University Hospital

    Seoul, 03080

  • Samsung Medical Center

    Seoul, 06351

  • Asan Medical Center.

    Seoul, 138-736

Other trials in South Korea

Hungary4 sites
  • Magyar Honvedseg Egeszsegugyi Kozpont

    Budapest, 1068

  • Peterfy Sandor utcai Korhaz-Rendelointezet es Baleseti Kozpont, Szemeszet KR

    Budapest, 1076

  • Semmelweis Egyetem Szemészeti Vizsgálóhely

    Budapest, 1085

  • Bajcsy-Zsilinszky Hospital

    Budapest, 1106

Other trials in Hungary

Portugal4 sites
  • Hospital de Braga

    Braga, 4710-243

  • AIBILI - Association for Innovation and Biomedical Research on Light

    Coimbra, 3000-548

  • Espaco Medico Coimbra

    Coimbra, 3030-163

  • Hospital de Santa Maria

    Lisbon, 1649-035

Other trials in Portugal

Russia4 sites
  • Intersec Research and Technology Complex ?Eye Microsurgery? n.a. S.N. Fyodorov

    Cheboksary, Mariy-El Republic, 428000

  • ?Intersec. Research and Technology Complex ?Eye Microsurgery? n a Fyodorov Irkutsk branch

    Irkutsk, 664033

  • Clinics of Eye Diseases, LLC

    Kazan', Tatarstan Republic, 420066

  • ?Intersec Research and Technology Complex Eye Microsurgery n a Fyodorov Novosibirsk Branch

    Novosibirsk, 630096

Other trials in Russia

Turkey (Türkiye)4 sites
  • Ankara University Medical Faculty; Department of Ophthalmology

    Ankara, 06340

  • Ankara Baskent University Medical Faculty; Department of Ophthalmology

    Ankara, 06490

  • Beyoglu Goz Training and Research Hospital; Department Of Ophthalmology

    Istanbul, 34421

  • Kocaeli Üniversitesi T?p Fakültesi; Department of Ophthalmology

    Kocaeli, 41380

Other trials in Turkey (Türkiye)

Denmark3 sites
  • Aalborg Universitetshospital

    Aalborg, 9000

  • Rigshospitalet Glostrup

    Glostrup Municipality, 2600

  • Sjællands Universitetshospital, Roskilde

    Roskilde, 4000

Other trials in Denmark

France3 sites
  • Chi De Creteil

    Créteil, 94010

  • Centre Ophtalmologique

    Paris, 75015

  • Centres Ophtalmologique St Exupéry

    Saint-Cyr-sur-Loire, 37540

Other trials in France

Singapore3 sites
  • National University Hospital

    Singapore, 119074

  • Singapore Eye Research Institute

    Singapore, 168751

  • Tan Tock Seng Hospital

    Singapore, 308433

Other trials in Singapore

Taiwan3 sites
  • National Taiwan University Hospital

    Taipei, 10002

  • Taipei Veterans General Hospital

    Taipei, 11217

  • Chang Gung Medical Foundation - Linkou

    Taoyuan, 333

Other trials in Taiwan

Thailand3 sites
  • King Chulalongkorn Memorial Hospital

    Bangkok, 10330

  • Rajavithi Hospital

    Bangkok, 10400

  • Maharaj Nakorn ChiangMai Hospital

    Chiang Mai, 50200

Other trials in Thailand

Hong Kong2 sites
  • The University of Hong Kong

    Hong Kong

  • Hong Kong Eye Hospital

    Mong Kok

Other trials in Hong Kong

Switzerland1 site
  • Vista Klinik Ophthalmologische Klinik

    Binningen, 4102

Other trials in Switzerland

About this study

Official title: A Phase III, Multicenter, Randomized, Double-Masked, Active Comparator-Controlled Study to Evaluate the Efficacy and Safety of Faricimab (RO6867461) in Patients With Diabetic Macular Edema (RHINE)

This study will evaluate the efficacy, safety, and pharmacokinetics of faricimab administered at 8-week intervals or as specified in the protocol following treatment initiation, compared with aflibercept once every 8 weeks (Q8W), in participants with diabetic macular edema (DME).

Being tested
Aflibercept, Faricimab, Sham Procedure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AfliberceptDrug

    Also called Eylea

    Aflibercept 2 mg was administered by intravitreal (IVT) injection into the study eye once every 8 weeks (Q8W).

  • FaricimabDrug

    Also called VABYSMO™, RO6867461, RG7716

    Faricimab 6 mg was administered by IVT injection into the study eye either once every 8 weeks (Q8W) in arm A or according to a personalized treatment interval (PTI) in arm B.

  • Sham ProcedureProcedure or surgery

    The sham is a procedure that mimics an IVT injection and involves the blunt end of an empty syringe (without a needle) being pressed against the anesthetized eye. It was administered to participants in all three treatments arms at applicable visits to maintain masking among treatment arms.

Study groups in NCT03622593
Study groupRoleWhat they receive
A: Faricimab 6 mg Q8WExperimentalParticipants randomized to Arm A received 6 milligrams (mg) faricimab intravitreal (IVT) injections once every 4 weeks (Q4W) to Week 20, followed by 6 mg faricimab IVT injections once every 8 weeks (Q8W) to Week 96, followed by the final study visit at Week 100.
Receives: Drug: Faricimab; Procedure: Sham Procedure
B: Faricimab 6 mg PTIExperimentalParticipants randomized to Arm B received 6 milligrams (mg) faricimab intravitreal (IVT) injections Q4W to at least Week 12, followed by a personalized treatment interval (PTI) dosing of 6 mg faricimab IVT injections up to once every 16 weeks (Q16W) through Week 96, followed by the final study visit at Week 100.
Receives: Drug: Faricimab; Procedure: Sham Procedure
C: Aflibercept 2 mg Q8WActive comparatorParticipants randomized to Arm C received 2 milligrams (mg) aflibercept intravitreal (IVT) injections Q4W to Week 16, followed by 2 mg aflibercept IVT injections Q8W to Week 96, followed by the final study visit at Week 100.
Receives: Drug: Aflibercept; Procedure: Sham Procedure

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change From Baseline in BCVA in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations

    Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. For the Mixed Model for Repeated Measures (MMRM) analysis, the model adjusted for treatment arm, visit, visit-by-treatment arm interaction, baseline BCVA (continuous), baseline BCVA (<64 vs. ≥64 letters), prior intravitreal anti-VEGF therapy (yes vs. no), and region of enrollment. An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. Invalid BCVA values were excluded. 97.5% CI is a rounding of 97.52% CI.

    Measured: From Baseline through Week 56

Secondary outcomes (59)
  1. Percentage of Participants With a ≥2-Step Diabetic Retinopathy Severity (DRS) Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale (DRSS) at Week 52, ITT and Treatment-Naive Populations

    The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 97.5% confidence interval (CI) is a rounding of 97.52% CI.

    Measured: Baseline and Week 52

  2. Change From Baseline in BCVA in the Study Eye Over Time, ITT Population

    Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. For the Mixed Model for Repeated Measures (MMRM) analysis, the model adjusted for treatment arm, visit, visit-by-treatment arm interaction, baseline BCVA (continuous), baseline BCVA (<64 vs. ≥64 letters), prior intravitreal anti-VEGF therapy (yes vs. no), and region of enrollment. An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. Invalid BCVA values were excluded. 95% CI is a rounding of 95.04% CI.

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

  3. Change From Baseline in BCVA in the Study Eye Over Time, Treatment-Naive Population

    Best-Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. For the Mixed Model for Repeated Measures (MMRM) analysis, the model adjusted for treatment group, visit, visit-by-treatment group interaction, baseline BCVA (continuous), baseline BCVA (<64 vs. ≥64 letters), and region of enrollment. An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

  4. Percentage of Participants Gaining Greater Than or Equal to (≥)15, ≥10, ≥5, or ≥0 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT Population

    BCVA was measured on the ETDRS chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Baseline, average of Weeks 48, 52, and 56

  5. Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population

    Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

  6. Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population

    Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

  7. Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population

    Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

  8. Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population

    Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

  9. Percentage of Participants Gaining ≥15, ≥10, ≥5, or ≥0 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, Treatment-Naive Population

    BCVA was measured on the ETDRS chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Baseline, average of Weeks 48, 52, and 56

  10. Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population

    Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

  11. Percentage of Participants Gaining ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population

    Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

  12. Percentage of Participants Gaining ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population

    Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

  13. Percentage of Participants Gaining ≥0 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population

    Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

  14. Percentage of Participants Avoiding a Loss of ≥15, ≥10, or ≥5 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT Population

    Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Baseline, average of Weeks 48, 52, and 56

  15. Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population

    Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The weighted estimates of the percentage of participants avoiding a loss of letters in BCVA from baseline were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

  16. Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population

    Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The weighted estimates of the percentage of participants avoiding a loss of letters in BCVA from baseline were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

  17. Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, ITT Population

    Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The weighted estimates of the percentage of participants avoiding a loss of letters in BCVA from baseline were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

  18. Percentage of Participants Avoiding a Loss of ≥15, ≥10, or ≥5 Letters in BCVA From Baseline in the Study Eye Averaged Over Weeks 48, 52, and 56, Treatment-Naive Population

    Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Baseline, average of Weeks 48, 52, and 56

  19. Percentage of Participants Avoiding a Loss of ≥15 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population

    Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The weighted estimates of the percentage of participants avoiding a loss of letters in BCVA from baseline were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

  20. Percentage of Participants Avoiding a Loss of ≥10 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population

    Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The weighted estimates of the percentage of participants avoiding a loss of letters in BCVA from baseline were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

  21. Percentage of Participants Avoiding a Loss of ≥5 Letters in BCVA From Baseline in the Study Eye Over Time, Treatment-Naive Population

    Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The weighted estimates of the percentage of participants avoiding a loss of letters in BCVA from baseline were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

  22. Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations

    BCVA was measured on the ETDRS chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Baseline, average of Weeks 48, 52, and 56

  23. Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, ITT Population

    Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

  24. Percentage of Participants Gaining ≥15 Letters in BCVA From Baseline or Achieving BCVA Snellen Equivalent of 20/20 or Better (BCVA ≥84 Letters) in the Study Eye Over Time, Treatment-Naive Population

    Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

  25. Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations

    BCVA was measured on the ETDRS chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥69 vs. <69 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Baseline, average of Weeks 48, 52, and 56

  26. Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, ITT Population

    Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥69 vs. <69 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

  27. Percentage of Participants With BCVA Snellen Equivalent of 20/40 or Better (BCVA ≥69 Letters) in the Study Eye Over Time, Treatment-Naive Population

    Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥69 vs. <69 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

  28. Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations

    BCVA was measured on the ETDRS chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA from baseline indicates an improvement in visual acuity. For each participant, an average BCVA value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Baseline, average of Weeks 48, 52, and 56

  29. Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, ITT Population

    Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score), and a gain in BCVA letter score from baseline indicates an improvement invisual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

  30. Percentage of Participants With BCVA Snellen Equivalent of 20/200 or Worse (BCVA ≤38 Letters) in the Study Eye Over Time, Treatment-Naive Population

    Best Corrected Visual Acuity (BCVA) was measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at a starting distance of 4 meters. The BCVA letter score ranges from 0 to 100 (best score attainable), and a gain in BCVA letter score from baseline indicates an improvement in visual acuity. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. Invalid BCVA values were excluded from analysis. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

  31. Percentage of Participants With a ≥2-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, ITT Population

    The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Baseline, Weeks 16, 52, and 96

  32. Percentage of Participants With a ≥2-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, Treatment-Naive Population

    The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Baseline, Weeks 16, 52, and 96

  33. Percentage of Participants With a ≥3-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, ITT Population

    The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Baseline, Weeks 16, 52, and 96

  34. Percentage of Participants With a ≥3-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, Treatment-Naive Population

    The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Baseline, Weeks 16, 52, and 96

  35. Percentage of Participants With a ≥4-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, ITT Population

    The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Baseline, Weeks 16, 52, and 96

  36. Percentage of Participants With a ≥4-Step Diabetic Retinopathy Severity Improvement From Baseline on the ETDRS Diabetic Retinopathy Severity Scale in the Study Eye Over Time, Treatment-Naive Population

    The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy. Ocular imaging assessments were made independently by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters) and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Baseline, Weeks 16, 52, and 96

  37. Percentage of Participants Without Proliferative Diabetic Retinopathy (PDR) at Baseline Who Developed New PDR at Week 52, ITT and Treatment-Naive Populations

    The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity steps ranging from absence of retinopathy to advanced proliferative diabetic retinopathy (PDR). PDR was defined as an ETDRS DRSS score of ≥61 on the 7-field/4-wide field color fundus photographs assessment by a central reading center. The weighted percentages of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% CI is a rounding of 95.04% CI.

    Measured: Baseline and Week 52

  38. Percentage of Participants Without High-Risk Proliferative Diabetic Retinopathy (PDR) at Baseline Who Developed High-Risk PDR at Week 52, ITT and Treatment-Naive Populations

    The Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) classifies diabetic retinopathy into 12 severity steps ranging from absence of retinopathy to advanced PDR. High-risk PDR was defined as an ETDRS DRSS score of ≥71 on the 7-field/4-wide field color fundus photographs assessment by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% CI is a rounding of 95.04% CI.

    Measured: Baseline and Week 52

  39. Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 52, ITT Population

    Measured: Week 52

  40. Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 52, Treatment-Naive Population

    Measured: Week 52

  41. Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 96, ITT Population

    Measured: Week 96

  42. Percentage of Participants in the Faricimab 6 mg PTI Arm on a Once Every 4-Weeks, 8-Weeks, 12-Weeks, or 16-Weeks Treatment Interval at Week 96, Treatment-Naive Population

    Measured: Week 96

  43. Percentage of Participants in the Faricimab 6 mg PTI Arm at Week 52 Who Achieved a Once Every 12-Weeks or 16-Weeks Treatment Interval Without an Interval Decrease Below Once Every 12 Weeks, ITT and Treatment-Naive Populations

    Measured: From start of PTI (Week 12 or later) until Week 52

  44. Percentage of Participants in the Faricimab 6 mg PTI Arm at Week 96 Who Achieved a Once Every 12-Weeks or 16-Weeks Treatment Interval Without an Interval Decrease Below Once Every 12 Weeks, ITT and Treatment-Naive Populations

    Measured: From start of PTI (Week 12 or later) until Week 96

  45. Change From Baseline in Central Subfield Thickness in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations

    Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and Bruch's membrane (BM) as assessed by a central reading center. For the Mixed Model for Repeated Measures (MMRM) analysis, the model adjusted for treatment group, visit, visit-by-treatment group interaction, baseline CST (continuous), baseline BCVA (<64 vs. ≥64 letters), prior intravitreal anti-VEGF therapy (yes vs. no), and region of enrollment (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: From Baseline through Week 56

  46. Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, ITT Population

    Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and Bruch's membrane (BM) as assessed by a central reading center. For the Mixed Model for Repeated Measures (MMRM) analysis, the model adjusted for treatment group, visit, visit-by-treatment group interaction, baseline CST (continuous), baseline BCVA (<64 vs. ≥64 letters), prior intravitreal anti-VEGF therapy (yes vs. no), and region of enrollment (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

  47. Change From Baseline in Central Subfield Thickness in the Study Eye Over Time, Treatment-Naive Population

    Central subfield thickness (CST) was defined as the distance between the internal limiting membrane (ILM) and Bruch's membrane (BM) as assessed by a central reading center. For the Mixed Model for Repeated Measures (MMRM) analysis, the model adjusted for treatment group, visit, visit-by-treatment group interaction, baseline CST (continuous), baseline BCVA (<64 vs. ≥64 letters), and region of enrollment (U.S. and Canada vs. the rest of the world; Asia and rest of the world regions were combined). An unstructured covariance structure was used. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

  48. Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations

    Absence of diabetic macular edema was defined as achieving a central subfield thickness (CST) of <325 microns in the study eye. CST was defined as the distance between the internal limiting membrane and Bruch's membrane. For each participant, an average CST value was calculated across the three visits, and this averaged value was then used to determine if the endpoint was met. The results were summarized as the percentage of participants per treatment arm who met the endpoint. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world). Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Average of Weeks 48, 52, and 56

  49. Percentage of Participants With Absence of Diabetic Macular Edema in the Study Eye Over Time, ITT Population

    Absence of diabetic macular edema was defined as achieving a central subfield thickness of <325 microns in the study eye. Central subfield thickness was defined as the distance between the internal limiting membrane (ILM) and Bruch's membrane (BM) as assessed by a central reading center. The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

  50. Percentage of Participants With Retinal Dryness in the Study Eye Over Time, ITT Population

    Retinal dryness was defined as achieving a central subfield thickness (ILM-BM) of <280 microns. Central subfield thickness was defined as the distance between the internal limiting membrane (ILM) and Bruch's membrane (BM) as assessed by a central reading center. The weighted estimates of the percentage of participants was based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world; Asia and rest of the world regions were combined). Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, and 100

  51. Percentage of Participants With Absence of Intraretinal Fluid in the Study Eye Over Time, ITT Population

    Intraretinal fluid was measured using optical coherence tomography (OCT) in the central subfield (center 1 mm). The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world); Asia and rest of the world regions were combined due to a small number of enrolled participants. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Baseline, Weeks 16, 48, 52, 56, 92, 96, and 100

  52. Percentage of Participants With Absence of Subretinal Fluid in the Study Eye Over Time, ITT Population

    Subretinal fluid was measured using optical coherence tomography (OCT) in the central subfield (center 1 mm). The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world); Asia and rest of the world regions were combined due to a small number of enrolled participants. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Baseline, Weeks 16, 48, 52, 56, 92, 96, and 100

  53. Percentage of Participants With Absence of Intraretinal Fluid and Subretinal Fluid in the Study Eye Over Time, ITT Population

    Intraretinal fluid and subretinal fluid were measured using optical coherence tomography (OCT) in the central subfield (center 1 mm). The weighted estimates of the percentage of participants were based on the Cochran-Mantel Haenszel (CMH) weights stratified by baseline BCVA (≥64 vs. <64 letters), prior IVT anti-VEGF therapy (yes vs. no), and region (U.S. and Canada vs. rest of the world); Asia and rest of the world regions were combined due to a small number of enrolled participants. Treatment policy strategy (i.e., all observed values used) and hypothetical strategy (i.e., all values censored after the occurrence of the intercurrent event) were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were not imputed. 95% confidence interval (CI) is a rounding of 95.04% CI.

    Measured: Baseline, Weeks 16, 48, 52, 56, 92, 96, and 100

  54. Change From Baseline in the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) Composite Score Over Time, ITT Population

    The NEI VFQ-25 captures a patient's perception of vision-related functioning and quality of life. The core measure includes 25 items that comprise 11 vision-related subscales and one item on general health. The composite score ranges from 0 to 100, with higher scores, or a positive change from baseline, indicating better vision-related functioning. For the Mixed Model for Repeated Measures (MMRM) analysis, the model adjusted for treatment arm, visit, visit-by-treatment arm interaction, baseline NEI VFQ-25 Composite Score (continuous), baseline BCVA (<64 vs. ≥64 letters), prior intravitreal anti-VEGF therapy (yes vs. no), and region of enrollment. An unstructured covariance structure was used. Treatment policy strategy and hypothetical strategy were applied to non-COVID-19 related and COVID-19 related intercurrent events, respectively. Missing data were implicitly imputed by MMRM. 95% CI is a rounding of 95.04% CI.

    Measured: Baseline, Weeks 24, 52, and 100

  55. Percentage of Participants With at Least One Adverse Event

    This analysis of adverse events (AEs) includes both ocular and non-ocular (systemic) AEs. Investigators sought information on AEs at each contact with the participants. All AEs were recorded and the investigator made an assessment of seriousness, severity, and causality of each AE. AEs of special interest included the following: Cases of potential drug-induced liver injury that include an elevated ALT or AST in combination with either an elevated bilirubin or clinical jaundice, as defined by Hy's Law; Suspected transmission of an infectious agent by the study drug; Sight-threatening AEs that cause a drop in visual acuity (VA) score ≥30 letters lasting more than 1 hour, require surgical or medical intervention to prevent permanent loss of sight, or are associated with severe intraocular inflammation.

    Measured: From first dose of study drug through end of study (up to 2 years)

  56. Percentage of Participants With at Least One Ocular Adverse Event in the Study Eye or the Fellow Eye

    This analysis of adverse events (AEs) only includes ocular AEs, which are categorized as having occurred either in the study eye or the fellow eye. Investigators sought information on AEs at each contact with the participants. All AEs were recorded and the investigator made an assessment of seriousness, severity, and causality of each AE. Ocular AEs of special interest included the following: Suspected transmission of an infectious agent by the study drug; Sight-threatening AEs that cause a drop in visual acuity (VA) score ≥30 letters lasting more than 1 hour, require surgical or medical intervention to prevent permanent loss of sight, or are associated with severe intraocular inflammation (IOI).

    Measured: From first dose of study drug through end of study (up to 2 years)

  57. Percentage of Participants With at Least One Non-Ocular Adverse Event

    This analysis of adverse events (AEs) only includes non-ocular (systemic) AEs. Investigators sought information on adverse events (AEs) at each contact with the participants. All AEs were recorded and the investigator made an assessment of seriousness, severity, and causality of each AE. The non-ocular AE of special interest was: Cases of potential drug-induced liver injury that include an elevated ALT or AST in combination with either an elevated bilirubin or clinical jaundice, as defined by Hy's Law.

    Measured: From first dose of study drug through end of study (up to 2 years)

  58. Plasma Concentration of Faricimab Over Time

    Faricimab concentration in plasma was determined using a validated immunoassay method.

    Measured: Pre-dose on Day 1 (Baseline); Weeks 4, 28, 52, 76, and 100

  59. Percentage of Participants Who Test Positive for Treatment-Emergent Anti-Drug Antibodies Against Faricimab During the Study

    Anti-drug antibodies (ADAs) against fariciamb were detected in plasma using a validated bridging enzyme-linked immunosorbent assay (ELISA). The percentage of participants with treatment-emergent ADA-positive samples includes post-baseline evaluable participants with at least one treatment-induced (defined as having an ADA-negative sample or missing sample at baseline and any positive post-baseline sample) or treatment-boosted (defined as having an ADA-positive sample at baseline and any positive post-baseline sample with a titer that is equal to or greater than 4-fold baseline titer) ADA-positive sample during the study treatment period.

    Measured: Baseline, Weeks 4, 28, 52, 76, and 100

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Aug 2018
  2. Study start9 Oct 2018
  3. Primary completion19 Oct 2020
  4. Study completion31 May 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
951 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03622593
Sponsor's protocol ID
GR40398
Other IDs
2017-005105-12, 2017
Acronym
RHINE
Status last verified
Jul 2025
First submitted
1 Aug 2018
Last updated
11 Jul 2025
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing

Publications

  • Wong TY, Haskova Z, Asik K, Baumal CR, Csaky KG, Eter N, Ives JA, Jaffe GJ, Korobelnik JF, Lin H, Murata T, Ruamviboonsuk P, Schlottmann PG, Seres AI, Silverman D, Sun X, Tang Y, Wells JA, Yoon YH, Wykoff CC; YOSEMITE and RHINE Investigators. Faricimab Treat-and-Extend for Diabetic Macular Edema: Two-Year Results from the Randomized Phase 3 YOSEMITE and RHINE Trials. Ophthalmology. 2024 Jun;131(6):708-723. doi: 10.1016/j.ophtha.2023.12.026. Epub 2023 Dec 28.

    PubMed 38158159
  • Wang Y, Hibar DP, Sadda S, Lim JI, Chan CK, Tan GS, Talcott KE, Gibson K, Maunz A, Lu H, Albrecht T, Amador M, Litts KM. Early Intraretinal Fluid Reduction is Linked to Vision Gains in Patients with Diabetic Macular Edema. Ophthalmol Ther. 2026 Sep 22. doi: 10.1007/s40123-026-01504-z. Online ahead of print.

    PubMed 42771326
  • Li X, Liu X, Jiang Q, Wu Z, Han M, Chen Q, Idowu OO, Liu R, Liu W, Willis JR, Sun X. Efficacy, Durability, and Safety of Faricimab for Diabetic Macular Edema: 1-Year Results from the China RHINE Subpopulation. Ophthalmol Ther. 2026 May;15(5):1761-1772. doi: 10.1007/s40123-026-01378-1. Epub 2026 Apr 10.

    PubMed 41961203
  • Sheth VS, Schlottmann P, Lai TYY, Abreu F, Chang A, Eter N, Gibson K, Hu AY, Korobelnik JF, Kotak A, Kotecha A, O'Leary OE, Pearce I, Sim DA, Sun JK, Tang Y, Khanani AM. Four-Year Outcomes of Faricimab in Diabetic Macular Edema: Results from the RHONE-X Extension Trial. Ophthalmology. 2026 May;133(5):599-612. doi: 10.1016/j.ophtha.2026.01.001. Epub 2026 Jan 12.

    PubMed 41534798
  • Jaffe GJ, Deak G, Gibson K, Khurana RN, Nudleman E, Ogura Y, Schmidt-Erfurth U, Wang T, Westenskow PD, Wong D, Yiu G, Willis JR. IMPACT OF FARICIMAB VERSUS AFLIBERCEPT ON EPIRETINAL MEMBRANE FORMATION OVER 2 YEARS IN PATIENTS WITH DIABETIC MACULAR EDEMA IN THE PHASE 3 YOSEMITE AND RHINE TRIALS. Retina. 2025 Nov 1;45(11):2003-2011. doi: 10.1097/IAE.0000000000004572.

    PubMed 40668667
  • Chakravarthy U, Chaudhary V, Sadda SR, Tan CS, Vujosevic S, Fauser S, Gibson K, Glittenberg C, Holekamp N, Lanza B, Maunz A, Willis JR, Singh RP. Effect of Faricimab versus Aflibercept on Hyperreflective Foci in Patients with Diabetic Macular Edema from the YOSEMITE/RHINE Trials. Ophthalmol Sci. 2025 Apr 19;5(5):100798. doi: 10.1016/j.xops.2025.100798. eCollection 2025 Sep-Oct.

    PubMed 40496217
  • Goldberg RA, Mar FA, Csaky K, Amador M, Khanani AM, Gibson K, Kolomeyer AM, Sim DA, Murata T, Wang T, Udaondo P, Souverain A, Shildkrot YE, Vujosevic S, Nudleman E, Sivaprasad S. Resolution of Angiographic Macular Leakage with Faricimab versus Aflibercept in Patients with Diabetic Macular Edema in YOSEMITE/RHINE. Ophthalmol Retina. 2025 Jun;9(6):515-526. doi: 10.1016/j.oret.2024.11.015. Epub 2024 Nov 22.

    PubMed 39580145
  • Zarbin M, Tabano D, Ahmed A, Amador M, Ding A, Holekamp N, Lu XY, Stoilov I, Yang M. Efficacy of Faricimab versus Aflibercept in Diabetic Macular Edema in the 20/50 or Worse Vision Subgroup in Phase III YOSEMITE and RHINE Trials. Ophthalmology. 2024 Nov;131(11):1258-1270. doi: 10.1016/j.ophtha.2024.05.025. Epub 2024 Jun 8.

    PubMed 38852921
  • von Schulthess EL, Maunz A, Chakravarthy U, Holekamp N, Pauleikhoff D, Patel K, Bachmeier I, Yu S, Cohen Y, Scherb MP, Jones IL, Gibson K, Willis JR, Glittenberg C, Singh RP, Fauser S. Intraretinal Hyper-Reflective Foci Are Almost Universally Present and Co-Localize With Intraretinal Fluid in Diabetic Macular Edema. Invest Ophthalmol Vis Sci. 2024 May 1;65(5):26. doi: 10.1167/iovs.65.5.26.

    PubMed 38758639
  • Stockwell AD, Chang MC, Mahajan A, Forrest W, Anegondi N, Pendergrass RK, Selvaraj S, Reeder J, Wei E, Iglesias VA, Creps NM, Macri L, Neeranjan AN, van der Brug MP, Scales SJ, McCarthy MI, Yaspan BL. Multi-ancestry GWAS analysis identifies two novel loci associated with diabetic eye disease and highlights APOL1 as a high risk locus in patients with diabetic macular edema. PLoS Genet. 2023 Aug 16;19(8):e1010609. doi: 10.1371/journal.pgen.1010609. eCollection 2023 Aug.

    PubMed 37585454
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Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Aflibercept and Faricimab in people with Diabetic Macular Edema, run by Hoffmann-La Roche at 188 sites in 24 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 188 sites in United States, United Kingdom, China, Canada, Brazil and 19 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Mar 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in BCVA in the Study Eye Averaged Over Weeks 48, 52, and 56, ITT and Treatment-Naive Populations (time frame: From Baseline through Week 56). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03622593, which also lists 13 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jul 2025.

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