Diabetic Macular EdemaPhase 3KESTRELNCT03481634
Study of Efficacy and Safety of Brolucizumab vs. Aflibercept in Patients With Visual Impairment Due to Diabetic Macular Edema
A Phase 3 study testing Brolucizumab and Aflibercept in people with Diabetic Macular Edema, run by Novartis Pharmaceuticals at 116 sites in 14 countries.
Trial summary
The purpose of this study was to evaluate the efficacy and safety of brolucizumab in treatment of patients with visual impairment due to 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?
- Brolucizumab and Aflibercept
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 566 participants
- Where
- 116 sitesin 14 countries
- Study dates
- 23 Jul 2018to 18 Oct 2021
- 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
- Written informed consent before any assessment
- Patients with type 1 or type 2 diabetes mellitus and HbA1c of ≤10% at screening
- Medication for the management of diabetes stable within 3 months prior to randomization and is expected to remain stable during the course of the study
Who cannot join
- Active proliferative diabetic retinopathy in the study eye
- Active intraocular or periocular infection or active intraocular inflammation in study eye
- Uncontrolled glaucoma in the study eye defined as intraocular pressure (IOP) > 25 millimeters mercury (mmHg)
- Previous treatment with anti-VEGF drugs or investigational drugs in the study eye
- Stroke or myocardial infarction during the 6-month period prior to baseline
- Uncontrolled blood pressure defined as a systolic value ≥160 mmHg or diastolic value ≥100 mmHg
- Other protocol-specified inclusion/exclusion criteria may apply
Trial locations and contacts
116 sites in 14 countries.
116 sites in 14 countries
United States39 sites
Novartis Investigative Site
‘Aiea, Hawaii, 96701
Novartis Investigative Site
Austin, Texas, 78705
Novartis Investigative Site
Austin, Texas, 78731
Novartis Investigative Site
Austin, Texas, 78750
Novartis Investigative Site
Bellaire, Texas, 77401
Novartis Investigative Site
Beverly Hills, California, 90211
Novartis Investigative Site
Cincinnati, Ohio, 45242
Novartis Investigative Site
Cleveland, Ohio, 44122
Novartis Investigative Site
Cleveland, Ohio, 44195
Novartis Investigative Site
Colorado Springs, Colorado, 80909
Novartis Investigative Site
Danbury, Connecticut, 06810
Novartis Investigative Site
Harlingen, Texas, 78550
Novartis Investigative Site
Houston, Texas, 77030
Novartis Investigative Site
Indianapolis, Indiana, 46280
Novartis Investigative Site
Kingston, Pennsylvania, 95403
Novartis Investigative Site
La Jolla, California, 92093
Novartis Investigative Site
Leawood, Kansas, 66211
Novartis Investigative Site
Lenexa, Kansas, 66215
Novartis Investigative Site
Madison, Wisconsin, 53705-3611
Novartis Investigative Site
Memphis, Tennessee, 38119
Novartis Investigative Site
Miami, Florida, 33136
Novartis Investigative Site
Mountain View, California, 94040
Novartis Investigative Site
Nashville, Tennessee, 37232
Novartis Investigative Site
New Albany, Indiana, 47150
Novartis Investigative Site
Paducah, Kentucky, 42001
Novartis Investigative Site
Pensacola, Florida, 32503
Novartis Investigative Site
Philadelphia, Pennsylvania, 19107
Novartis Investigative Site
Phoenix, Arizona, 85053
Novartis Investigative Site
Reno, Nevada, 89502
Novartis Investigative Site
San Antonio, Texas, 78240
Novartis Investigative Site
Santa Barbara, California, 93103
Novartis Investigative Site
Silverdale, Washington, 98383
Novartis Investigative Site
Spokane, Washington, 99204
Novartis Investigative Site
Springfield, Massachusetts, 01107
Novartis Investigative Site
Stoneham, Massachusetts, 02180
Novartis Investigative Site
Stuart, Florida, 34994
Novartis Investigative Site
Tyler, Texas, 75701
Novartis Investigative Site
Urbana, Illinois, 61801
Novartis Investigative Site
Wheaton, Illinois, 60187
Japan18 sites
Novartis Investigative Site
Amagasaki, Hyōgo, 660 8550
Novartis Investigative Site
Chiyoda-ku, Tokyo, 101-8309
Novartis Investigative Site
Hachiōji, Tokyo, 193-0944
Novartis Investigative Site
Ishioka, Ibaraki, 315-0037
Novartis Investigative Site
Kagoshima, Kagoshima-ken, 890 8520
Novartis Investigative Site
Kumamoto
Novartis Investigative Site
Kurume, Fukuoka, 830-8543
Novartis Investigative Site
Matsumoto, Nagano, 390-8621
Novartis Investigative Site
Nagoya, Aichi-ken, 455-8530
Novartis Investigative Site
Nagoya, Aichi-ken, 457-8511
Novartis Investigative Site
Nagoya, Aichi-ken, 462-0825
Novartis Investigative Site
Nagoya, Aichi-ken, 466 8560
Novartis Investigative Site
Osaka, 543-0027
Novartis Investigative Site
Saitama-shi, Saitama, 336-0963
Novartis Investigative Site
Shimotsuke, Tochigi, 329-0498
Novartis Investigative Site
Shinjuku Ku, Tokyo, 162 8666
Novartis Investigative Site
Taito-ku, Tokyo, 111-0051
Novartis Investigative Site
Tsuchiura, Ibaragi, 300-0817
Australia8 sites
Novartis Investigative Site
Adelaide, South Australia, 5000
Novartis Investigative Site
Clayton, Victoria, 3168
Novartis Investigative Site
Liverpool, New South Wales, 2170
Novartis Investigative Site
Melbourne, Victoria, 3002
Novartis Investigative Site
Nedlands, Western Australia, 6009
Novartis Investigative Site
Parramatta, New South Wales, 2150
Novartis Investigative Site
Sydney, New South Wales, 2000
Novartis Investigative Site
Westmead, New South Wales, 2145
Israel8 sites
Novartis Investigative Site
Haifa, 3109601
Novartis Investigative Site
Haifa, 3339419
Novartis Investigative Site
Haifa, 3436212
Novartis Investigative Site
Jerusalem, 9112001
Novartis Investigative Site
Kfar Saba, 4428164
Novartis Investigative Site
Petah Tikva, 4941492
Novartis Investigative Site
Rehovot, 7610001
Novartis Investigative Site
Tel Aviv, 6423906
Portugal7 sites
Novartis Investigative Site
Coimbra, 3000-548
Novartis Investigative Site
Coimbra, 3030-363
Novartis Investigative Site
Leiria, 2410-187
Novartis Investigative Site
Porto, 4099-001
Novartis Investigative Site
Porto, 4200 319
Novartis Investigative Site
Santa Maria da Feira, 4520 211
Novartis Investigative Site
Vila Franca de Xira, 2600-009
Italy6 sites
Novartis Investigative Site
Catania, CT, 95124
Novartis Investigative Site
Chieti, CH, 66100
Novartis Investigative Site
Milan, MI, 20100
Novartis Investigative Site
Milan, MI, 20132
Novartis Investigative Site
Padova, PD, 35128
Novartis Investigative Site
Roma, RM, 00144
Spain6 sites
Novartis Investigative Site
Barcelona, Catalonia, 08036
Novartis Investigative Site
Barcelona, 08025
Novartis Investigative Site
Sant Cugat del Vallès, Catalonia, 08190
Novartis Investigative Site
Valencia, Valencia, 46014
Novartis Investigative Site
Valladolid, Castille and León, 47011
Novartis Investigative Site
Zaragoza, 50009
Argentina5 sites
Novartis Investigative Site
CABA, 1425
Novartis Investigative Site
CABA
Novartis Investigative Site
Ciudad Autonoma de Bs As, Buenos Aires, C1015ABO
Novartis Investigative Site
Córdoba, X5000AAJ
Novartis Investigative Site
Rosario, Santa Fe Province
United Kingdom5 sites
Novartis Investigative Site
Birmingham, B18 7QH
Novartis Investigative Site
Frimley, Surrey, GU16 7UJ
Novartis Investigative Site
Hull, HU3 2JZ
Novartis Investigative Site
London, NW10 7NS
Novartis Investigative Site
Nottingham, NG7 2UH
Canada4 sites
Novartis Investigative Site
Ottawa, Ontario, K1Z 8R2
Novartis Investigative Site
Québec, G1S 4L8
Novartis Investigative Site
Toronto, Ontario, M4N 3M5
Novartis Investigative Site
Toronto, Ontario, M5C 2T2
Austria3 sites
Novartis Investigative Site
Graz, A-8036
Novartis Investigative Site
Innsbruck, 6020
Novartis Investigative Site
Vienna, 1090
Colombia3 sites
Novartis Investigative Site
Bogotá, 110221
Novartis Investigative Site
Medellín, Antioquia, 001
Novartis Investigative Site
Medellín, Antioquia
Netherlands3 sites
Novartis Investigative Site
Amsterdam, 1105 AZ
Novartis Investigative Site
Rotterdam, 3011 BH
Novartis Investigative Site
Tilburg, 5022 GC
About this study
Official title: A Two-year, Three-arm, Randomized, Double-masked, Multicenter, Phase III Study Assessing the Efficacy and Safety of Brolucizumab Versus Aflibercept in Adult Patients With Visual Impairment Due to Diabetic Macular Edema
The purpose of this study was to evaluate the efficacy and safety of brolucizumab in treatment of patients with visual impairment due to diabetic macular edema (DME).
Read the detailed description
This was a Phase III, randomized, double-masked, multi-center, active-controlled, three-arm study designed to evaluate the efficacy and safety of brolucizumab 6 mg and 3 mg compared to the active control, aflibercept 2 mg used per authorized label, in subjects with diabetic macular edema (DME). The study included a screening period of up to 2 weeks to assess eligibility, followed by a doublemasked treatment period (Day 1 to Week 96). The baseline visit was defined as Day 1/Visit 1, and end of treatment visit as Visit 27 (Week 96). After the last treatment visit, a post-treatment follow-up period was planned from Week 96 to Week 100.
Subjects were assigned to one of three treatment arms in a 1:1:1 ratio: brolucizumab 6 mg/0.05 mL administered 5 x every 6 weeks (q6w) during loading phase then q12w/every 8 weeks (q8w) during maintenance phase, brolucizumab 3 mg/0.05 mL administered 5 x every 6 weeks (q6w) during loading phase then q12w/q8w during maintenance phase or aflibercept 2 mg/0.05 mL administered 5 x every 4 weeks (q4w) during loading phase then q8w during maintenance phase.
Disease Activity Assessments (DAAs) were conducted by the masked investigator for each treatment arm at Week 32 and Week 36, i.e. 8 and 12 weeks after the end of the loading phase for subjects receiving brolucizumab. Assessments were also performed at Week 48, and will then continue to be performed from Week 60 up to Week 96, every 12 weeks. Subjects in the brolucizumab arms who qualified for q12w during the initial q12w interval continued on a q12w treatment frequency unless disease activity was identified at any of the subsequent DAA visits, in which case subjects were switched to a q8w treatment interval until the end of the study.
To fulfil the double-masking requirement, each investigational site had masked and unmasked staff. The investigator who performed the injection was unmasked to the treatments as were any other site personnel who had been delegated responsibility for working with the Investigational Product (IP). The unmasked site personnel and unmasked injecting investigator did not perform Best-corrected visual acuity (BCVA), complete ophthalmic examination (with the exception of post-injection safety assessment), DAAs or administer the Visual Functioning Questionnaire-25 (VFQ-25). Also, the unmasked site personnel and unmasked injecting physician did not perform assessment of any ocular or non-ocular safety parameters, or assess causality of Adverse event (AEs) for subjects during the course of the study except an event reported immediately following Intravitreal treatment (IVT). Once the designated roles were determined, the unmasked investigator/site personnel roles were not switched at any time after randomization to masked role. Every effort was made to limit the number of unmasked study personnel to ensure the integrity of this masked study.
- Conditions
- Diabetic Macular Edema
- Being tested
- Brolucizumab, Aflibercept
- Keywords
- Diabetic Macular Edema, intravitreal injection, brolucizumab, aflibercept, double-masked, Diabetic Macular Edema (DME), macular edema, diabetic retinopathy
- Medical subject headings
- Macular Edema, Diabetic Retinopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BrolucizumabDrug
Also called RTH258, ESBA1008
Intravitreal injection
AfliberceptDrug
Also called Eylea
Intravitreal injection
| Study group | Role | What they receive |
|---|---|---|
| Brolucizumab 3 mg | Experimental | Brolucizumab 3 mg/0.05 mL, 5 loading doses, with subsequent doses per protocol-specified maintenance schedule.
To fulfil the double-masking requirement, each investigational site had masked and unmasked staff. The investigator who performed the injection was unmasked to the treatments as were any other site personnel who had been delegated responsibility for working with the Investigational Product (IP). Receives: Drug: Brolucizumab |
| Brolucizumab 6 mg | Experimental | Brolucizumab 6 mg/0.05 mL, 5 loading doses, with subsequent doses per protocol-specified maintenance schedule.
To fulfil the double-masking requirement, each investigational site had masked and unmasked staff. The investigator who performed the injection was unmasked to the treatments as were any other site personnel who had been delegated responsibility for working with the Investigational Product (IP). Receives: Drug: Brolucizumab |
| Aflibercept 2 mg | Active comparator | Aflibercept 2 mg/0.05 mL, as labeled, 5 loading doses, with subsequent doses every 8 weeks.
To fulfil the double-masking requirement, each investigational site had masked and unmasked staff. The investigator who performed the injection was unmasked to the treatments as were any other site personnel who had been delegated responsibility for working with the Investigational Product (IP). Receives: Drug: Aflibercept |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Best-corrected Visual Acuity (BCVA) at Week 52
BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts.
Visual Function of the study eye was assessed using the ETDRS protocol. Participants with a BCVA ETDRS letter score of 78 to 23 (approximate Snellen equivalent of 20/32 to 20/320) in the study eye were included.
Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.
This endpoint was analyzed via the pairwise ANOVA method where the 2 dose groups of Brolucizumab are compared to Aflibercept.
Measured: Baseline, Week 52
Secondary outcomes (33)
Average Change From Baseline in BCVA Over the Period Week 40 Through Week 52
BCVA will be assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts.
Visual function of the study eye was assessed using the ETDRS protocol. Participants with a BCVA ETDRS letter score of 78 to 23 (per the inclusion criteria) (approximate Snellen equivalent of 20/32 to 20/320) in the study eye were included.
Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.
This endpoint was analyzed via the pairwise ANOVA method where the 2 dose groups of Brolucizumab are compared to Aflibercept.
Measured: Baseline and Week 40 through Week 52 (average)
Patients Maintained at q12w - Probability of Maintaining on q12w
Positive treatment status is defined as intravitreal (IVT) injections per planned dosing regimen [every 12 weeks (q12w)]. This outcome measure is pre-specified for brolucizumab treatment arms only.
Measured: Baseline (Week 0), Weeks 32, 36 and 48
Patients Maintained at q12w (for Those Patients Who Qualified for q12w at Week 36) - Probability of Maintaining on q12w
Positive treatment status is defined as intravitreal (IVT) injections per planned dosing regimen [every 8 weeks (q8w)]. This outcome measure is pre-specified for brolucizumab treatment arms only.
Measured: Weeks 36 and 48
Change From Baseline in BCVA at Each Visit up to Week 52
BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts.
Visual function of the study eye was assessed using the ETDRS protocol. Participants with a BCVA ETDRS letter score of 78 to 23 (approximate Snellen equivalent of 20/32 to 20/320) in the study eye were included.
Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning.
Measured: Baseline (Week 0), Weeks 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48, and 52
BCVA (Letters Read): ANOVA Results for Average Change From Baseline Over the Period Week 88 Through Week 100 for the Study Eye (FAS - LOCF)
Visual acuity was assessed at every study visit using best correction determined from protocol refraction (BCVA). BCVA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts.
LS Mean estimates are reported, comparing the 2 Brolucizumab arms to Aflibercept. Results do not apply to the Brolucizumab 6 mg arm when Brolucizumab 3mg is compared to Aflibercept. Likewise, results do not apply to the Brolucizumab 3 mg arm when Brolucizumab 6 mg is compared to Aflibercept.
Measured: Baseline, and Week 88 through Week 100 (average)
Patients Maintained at q12w up to Week 64 (After Three q12w- Treatment Intervals) and Week 100 - Probability of Maintaining on q12w
This outcome measure is pre-specified for brolucizumab treatment arms only
Measured: Baseline (Week 0), Weeks 32, 36, 48, 60, 72, 84, and 96
Secondary: Patients Maintained at q12w up to Week 64 (After Three q12w- Treatment Intervals) and Week 100, Within Those Patients That Qualified for q12w at Week 36 - Probability of Maintaining on q12w
This outcome measure is pre-specified for brolucizumab treatment arms only
Measured: Baseline (Week 0), Weeks 32, 36, 48, 60, 72, 84, and 96
Change From Baseline in Central Subfield Thickness (CSFT) at Each Visit up to Week 52 - Pairwise ANOVA Results
Central Subfield Thickness Assessed by Spectral domain optical coherence tomography (SD-OCT) from the central reading center.
LS Mean estimates are reported, comparing the 2 Brolucizumab arms to Aflibercept. Results do not apply to the Brolucizumab 6 mg arm when Brolucizumab 3mg is compared to Aflibercept. Likewise, results do not apply to the Brolucizumab 3 mg arm when Brolucizumab 6 mg is compared to Aflibercept.
Measured: Baseline up to week 52
Central Subfield Thickness (CSFT) (Micrometers): ANOVA Results for Average Change From Baseline Over the Period Week 88 Through Week 100 for the Study Eye (Full Analysis Set - LOCF)
Central subfield thickness (average thickness of circular 1mm area centered around fovea measured from RPE to ILM, inclusively). Assessed with Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts.
LS Mean estimates are reported, comparing the 2 Brolucizumab arms to Aflibercept. Results do not apply to the Brolucizumab 6 mg arm when Brolucizumab 3mg is compared to Aflibercept. Likewise, results do not apply to the Brolucizumab 3 mg arm when Brolucizumab 6 mg is compared to Aflibercept.
Measured: Baseline, and Week 88 through Week 100 (average)
Number of Patients With Presence of Subretinal Fluid (SRF) at Each Assessment Visit
Subretinal Fluid (SRF) status in the central subfield: proportion of subjects with presence of SRF in the study eye by visit
Measured: Baseline up to Week 52 and Week 100
Number of Patients With Presence of Intraretinal Fluid (IRF) at Each Assessment Visit
Intraretinal Fluid (IRF) status in the central subfield: proportion of subjects with presence of IRF in the study eye by visit
Measured: Baseline, up to Week 52 and Week 100
Number of Patients With Presence of SRF and/or IRF in the Study Eye by Visit
Subretinal Fluid (SRF) and Intraretinal Fluid (IRF) status in the central subfield: proportion of subjects with presence of SRF and/or IRF in the study eye by visit
Measured: Baseline, up to Week 52 and Week 100
Number of Patients With Presence of Leakage on Fluorescein Angiography (FA) at Week 52
Assessed by angiography.
Measured: Week 52
Number of Patients With Presence of Leakage on Fluorescein Angiography (FA) at Week 100
Assessed by angiography.
Measured: Week 100
Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS): Number of Subjects With >=2-step Improvement From Baseline in the DRSS Score at Each Assessment Visit for the Study Eye - Number of Subjects
Severity of Diabetic Retinopathy (DR) was evaluated using the ETDRS DRSS score assessed by the Central Reading Center (CRC) based on color fundus photography images in the study eye. When the ETDRS-DR severities were evaluable, they were categorized on a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR). A lower score represents better visual functioning.
Measured: Baseline, Weeks 28, 52, 76, 100
Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS): Proportion of Subjects With >=2-step Improvement From Baseline in the DRSS Score at Each Assessment Visit for the Study Eye - Percentage Estimates
Severity of Diabetic Retinopathy (DR) was evaluated using the ETDRS DRSS score assessed by the Central Reading Center (CRC) based on color fundus photography images in the study eye. When the ETDRS-DR severities were evaluable, they were categorized on a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR). A lower score represents better visual functioning.
- estimates are reported, comparing the 2 Brolucizumab arms to Aflibercept. Results do not apply to the Brolucizumab 6 mg arm when Brolucizumab 3mg is compared to Aflibercept. Likewise, results do not apply to the Brolucizumab 3 mg arm when Brolucizumab 6 mg is compared to Aflibercept.
- estimates represent the % of participants who were estimated to have a ">=2-step Improvement From Baseline in the DRSS Score" from pairwise logistic regression models adjusting for baseline DRSS score categories (<=4, ≥5), age categories (<65, ≥65 years) and treatment as fixed effect factors.
Abbreviation: Proportion Estimates = P.E.
Measured: Baseline, Weeks 28, 52, 76, 100
Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS): Number of Subjects With >=3-step Improvement From Baseline in the DRSS Score at Each Assessment Visit for the Study Eye - Number of Subjects
Severity of Diabetic Retinopathy (DR) was evaluated using the ETDRS DRSS score assessed by the Central Reading Center (CRC) based on color fundus photography images in the study eye. When the ETDRS-DR severities were evaluable, they were categorized on a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR). A lower score represents better visual functioning.
Measured: Baseline, Weeks 28, 52, 76, 100
Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS): Proportion of Subjects With >=3-step Improvement From Baseline in the DRSS Score at Each Assessment Visit for the Study Eye - Percentage Estimates
Severity of Diabetic Retinopathy (DR) was evaluated using the ETDRS DRSS score assessed by the Central Reading Center (CRC) based on color fundus photography images in the study eye. When the ETDRS-DR severities were evaluable, they were categorized on a 12-level scale, from 1 (DR absent) to 12 (very advanced PDR). A lower score represents better visual functioning.
- estimates are reported, comparing the 2 Brolucizumab arms to Aflibercept. Results do not apply to the Brolucizumab 6 mg arm when Brolucizumab 3mg is compared to Aflibercept. Likewise, results do not apply to the Brolucizumab 3 mg arm when Brolucizumab 6 mg is compared to Aflibercept.
- estimates represent the % of participants who were estimated to have a ">=3-step Improvement From Baseline in the DRSS Score" from pairwise logistic regression models adjusting for baseline DRSS score categories (<=4, ≥5), age categories (<65, ≥65 years) and treatment as fixed effect factors.
Abbreviation: Proportion Estimates = P.E.
Measured: Baseline, Weeks 28, 52, 76, 100
Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Composite Score
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains.
The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales.
Measured: Baseline, Weeks 28, 52, 76, 100
Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - General Vision
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains.
The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales.
Measured: Baseline, Weeks 28, 52, 76, 100
Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Ocular Pain
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains.
The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales.
Measured: Baseline, Weeks 28, 52, 76, 100
Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Near Activities
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains.
The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales.
Measured: Baseline, Weeks 28, 52, 76, 100
Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Distance Activities
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains.
The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales.
Measured: Baseline, Weeks 28, 52, 76, 100
Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Social Functioning
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains.
The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales.
Measured: Baseline, Weeks 28, 52, 76, 100
Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Mental Health
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains.
The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales.
Measured: Baseline, Weeks 28, 52, 76, 100
Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Role Difficulties
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains.
The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales.
Measured: Baseline, Weeks 28, 52, 76, 100
Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Dependency
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains.
The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales.
Measured: Baseline, Weeks 28, 52, 76, 100
Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Driving
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains.
The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales.
Measured: Baseline, Weeks 28, 52, 76, 100
Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Color Vision
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains.
The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales.
Measured: Baseline, Weeks 28, 52, 76, 100
Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Peripheral Vision
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains.
The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales.
Measured: Baseline, Weeks 28, 52, 76, 100
Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - General Health Rating
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures the influence of visual disability and visual symptoms on general health domains.
The NEI VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. All items are scored so that a high score represents better visual functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. A composite score is derived based on the average of the 11 subscales.
Measured: Baseline, Weeks 28, 52, 76, 100
Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye
Measured: Adverse events were reported from first dose of study treatment until Week 96, plus 30 days post treatment, up to a maximum duration of 100 weeks.
Number of Subjects With Non-ocular Adverse Events (AEs) (>=2% in Any Treatment Arm)
Measured: Adverse events were reported from first dose of study treatment until Week 96, plus 30 days post treatment, up to a maximum duration of 100 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2018
- Study start23 Jul 2018
- Primary completion11 Nov 2020
- Study completion18 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Diabetic Macular EdemaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 566 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03481634
- Sponsor's protocol ID
- CRTH258B2301
- Other IDs
- 2017-004742-23, 2017
- Acronym
- KESTREL
- Status last verified
- Jan 2023
- First submitted
- 13 Mar 2018
- Last updated
- 30 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Two-year, Three-arm, Randomized, Double-masked, Multicenter, Phase III Study Assessing the Efficacy and Safety of Brolucizumab Versus Aflibercept in Adult Patients With Visual Impairment Due to Diabetic Macular Edema
- ClinicalTrials.gov ID
- NCT03481634
- Acronym / sponsor ID
- KESTREL / CRTH258B2301
- Conditions
- Diabetic Macular Edema
- Keywords
- Diabetic Macular Edema, intravitreal injection, brolucizumab, aflibercept, double-masked, Diabetic Macular Edema (DME), macular edema, diabetic retinopathy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 566 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 23 Jul 2018 (actual)
- Primary completion
- 11 Nov 2020 (actual)
- Study completion
- 18 Oct 2021 (actual)
- First posted
- 29 Mar 2018 (actual)
- Results
- Posted 28 Oct 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study was to evaluate the efficacy and safety of brolucizumab in treatment of patients with visual impairment due to diabetic macular edema (DME).
Detailed description
This was a Phase III, randomized, double-masked, multi-center, active-controlled, three-arm study designed to evaluate the efficacy and safety of brolucizumab 6 mg and 3 mg compared to the active control, aflibercept 2 mg used per authorized label, in subjects with diabetic macular edema (DME). The study included a screening period of up to 2 weeks to assess eligibility, followed by a doublemasked treatment period (Day 1 to Week 96). The baseline visit was defined as Day 1/Visit 1, and end of treatment visit as Visit 27 (Week 96). After the last treatment visit, a post-treatment follow-up period was planned from Week 96 to Week 100.
Subjects were assigned to one of three treatment arms in a 1:1:1 ratio: brolucizumab 6 mg/0.05 mL administered 5 x every 6 weeks (q6w) during loading phase then q12w/every 8 weeks (q8w) during maintenance phase, brolucizumab 3 mg/0.05 mL administered 5 x every 6 weeks (q6w) during loading phase then q12w/q8w during maintenance phase or aflibercept 2 mg/0.05 mL administered 5 x every 4 weeks (q4w) during loading phase then q8w during maintenance phase.
Disease Activity Assessments (DAAs) were conducted by the masked investigator for each treatment arm at Week 32 and Week 36, i.e. 8 and 12 weeks after the end of the loading phase for subjects receiving brolucizumab. Assessments were also performed at Week 48, and will then continue to be performed from Week 60 up to Week 96, every 12 weeks. Subjects in the brolucizumab arms who qualified for q12w during the initial q12w interval continued on a q12w treatment frequency unless disease activity was identified at any of the subsequent DAA visits, in which case subjects were switched to a q8w treatment interval until the end of the study.
To fulfil the double-masking requirement, each investigational site had masked and unmasked staff. The investigator who performed the injection was unmasked to the treatments as were any other site personnel who had been delegated responsibility for working with the Investigational Product (IP). The unmasked site personnel and unmasked injecting investigator did not perform Best-corrected visual acuity (BCVA), complete ophthalmic examination (with the exception of post-injection safety assessment), DAAs or administer the Visual Functioning Questionnaire-25 (VFQ-25). Also, the unmasked site personnel and unmasked injecting physician did not perform assessment of any ocular or non-ocular safety parameters, or assess causality of Adverse event (AEs) for subjects during the course of the study except an event reported immediately following Intravitreal treatment (IVT). Once the designated roles were determined, the unmasked investigator/site personnel roles were not switched at any time after randomization to masked role. Every effort was made to limit the number of unmasked study personnel to ensure the integrity of this masked study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Brolucizumab 3 mg | Experimental | Drug: BrolucizumabBrolucizumab 3 mg/0.05 mL, 5 loading doses, with subsequent doses per protocol-specified maintenance schedule. To fulfil the double-masking requirement, each investigational site had masked and unmasked staff. The investigator who performed the injection was unmasked to the treatments as were any other site personnel who had been delegated responsibility for working with the Investigational Product (IP). |
| Brolucizumab 6 mg | Experimental | Drug: BrolucizumabBrolucizumab 6 mg/0.05 mL, 5 loading doses, with subsequent doses per protocol-specified maintenance schedule. To fulfil the double-masking requirement, each investigational site had masked and unmasked staff. The investigator who performed the injection was unmasked to the treatments as were any other site personnel who had been delegated responsibility for working with the Investigational Product (IP). |
| Aflibercept 2 mg | Active comparator | Drug: AfliberceptAflibercept 2 mg/0.05 mL, as labeled, 5 loading doses, with subsequent doses every 8 weeks. To fulfil the double-masking requirement, each investigational site had masked and unmasked staff. The investigator who performed the injection was unmasked to the treatments as were any other site personnel who had been delegated responsibility for working with the Investigational Product (IP). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Written informed consent before any assessment
- Patients with type 1 or type 2 diabetes mellitus and HbA1c of ≤10% at screening
- Medication for the management of diabetes stable within 3 months prior to randomization and is expected to remain stable during the course of the study
Key exclusion criteria (7 listed)
- Active proliferative diabetic retinopathy in the study eye
- Active intraocular or periocular infection or active intraocular inflammation in study eye
- Uncontrolled glaucoma in the study eye defined as intraocular pressure (IOP) > 25 millimeters mercury (mmHg)
- Previous treatment with anti-VEGF drugs or investigational drugs in the study eye
- Stroke or myocardial infarction during the 6-month period prior to baseline
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BrolucizumabAlso: RTH258, ESBA1008Intravitreal injection | Drug | Brolucizumab 3 mg, Brolucizumab 6 mg |
| AfliberceptAlso: EyleaIntravitreal injection | Drug | Aflibercept 2 mg |
Primary outcome
Change From Baseline in Best-corrected Visual Acuity (BCVA) at Week 52
Time frame: Baseline, Week 52
BCVA was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts. Visual Function of the study eye was assessed using the ETDRS protocol. Participants with a BCVA ETDRS letter score of 78 to 23 (approximate Snellen equivalent of 20/32 to 20/320) in the study eye were included. Min and max possible scores are 0-100 respectively. A higher score represents better visual functioning. This endpoint was analyzed via the pairwise ANOVA method where the 2 dose groups of Brolucizumab are compared to Aflibercept.
33 secondary outcomes
Average Change From Baseline in BCVA Over the Period Week 40 Through Week 52
Time frame: Baseline and Week 40 through Week 52 (average)
Patients Maintained at q12w - Probability of Maintaining on q12w
Time frame: Baseline (Week 0), Weeks 32, 36 and 48
Patients Maintained at q12w (for Those Patients Who Qualified for q12w at Week 36) - Probability of Maintaining on q12w
Time frame: Weeks 36 and 48
Change From Baseline in BCVA at Each Visit up to Week 52
Time frame: Baseline (Week 0), Weeks 4, 6, 8, 12, 16, 18, 20, 24, 28, 32, 36, 40, 44, 48, and 52
BCVA (Letters Read): ANOVA Results for Average Change From Baseline Over the Period Week 88 Through Week 100 for the Study Eye (FAS - LOCF)
Time frame: Baseline, and Week 88 through Week 100 (average)
Patients Maintained at q12w up to Week 64 (After Three q12w- Treatment Intervals) and Week 100 - Probability of Maintaining on q12w
Time frame: Baseline (Week 0), Weeks 32, 36, 48, 60, 72, 84, and 96
Secondary: Patients Maintained at q12w up to Week 64 (After Three q12w- Treatment Intervals) and Week 100, Within Those Patients That Qualified for q12w at Week 36 - Probability of Maintaining on q12w
Time frame: Baseline (Week 0), Weeks 32, 36, 48, 60, 72, 84, and 96
Change From Baseline in Central Subfield Thickness (CSFT) at Each Visit up to Week 52 - Pairwise ANOVA Results
Time frame: Baseline up to week 52
Central Subfield Thickness (CSFT) (Micrometers): ANOVA Results for Average Change From Baseline Over the Period Week 88 Through Week 100 for the Study Eye (Full Analysis Set - LOCF)
Time frame: Baseline, and Week 88 through Week 100 (average)
Number of Patients With Presence of Subretinal Fluid (SRF) at Each Assessment Visit
Time frame: Baseline up to Week 52 and Week 100
Number of Patients With Presence of Intraretinal Fluid (IRF) at Each Assessment Visit
Time frame: Baseline, up to Week 52 and Week 100
Number of Patients With Presence of SRF and/or IRF in the Study Eye by Visit
Time frame: Baseline, up to Week 52 and Week 100
Number of Patients With Presence of Leakage on Fluorescein Angiography (FA) at Week 52
Time frame: Week 52
Number of Patients With Presence of Leakage on Fluorescein Angiography (FA) at Week 100
Time frame: Week 100
Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS): Number of Subjects With >=2-step Improvement From Baseline in the DRSS Score at Each Assessment Visit for the Study Eye - Number of Subjects
Time frame: Baseline, Weeks 28, 52, 76, 100
Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS): Proportion of Subjects With >=2-step Improvement From Baseline in the DRSS Score at Each Assessment Visit for the Study Eye - Percentage Estimates
Time frame: Baseline, Weeks 28, 52, 76, 100
Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS): Number of Subjects With >=3-step Improvement From Baseline in the DRSS Score at Each Assessment Visit for the Study Eye - Number of Subjects
Time frame: Baseline, Weeks 28, 52, 76, 100
Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS): Proportion of Subjects With >=3-step Improvement From Baseline in the DRSS Score at Each Assessment Visit for the Study Eye - Percentage Estimates
Time frame: Baseline, Weeks 28, 52, 76, 100
Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Composite Score
Time frame: Baseline, Weeks 28, 52, 76, 100
Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - General Vision
Time frame: Baseline, Weeks 28, 52, 76, 100
Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Ocular Pain
Time frame: Baseline, Weeks 28, 52, 76, 100
Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Near Activities
Time frame: Baseline, Weeks 28, 52, 76, 100
Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Distance Activities
Time frame: Baseline, Weeks 28, 52, 76, 100
Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Social Functioning
Time frame: Baseline, Weeks 28, 52, 76, 100
Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Mental Health
Time frame: Baseline, Weeks 28, 52, 76, 100
Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Role Difficulties
Time frame: Baseline, Weeks 28, 52, 76, 100
Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Dependency
Time frame: Baseline, Weeks 28, 52, 76, 100
Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Driving
Time frame: Baseline, Weeks 28, 52, 76, 100
Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Color Vision
Time frame: Baseline, Weeks 28, 52, 76, 100
Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - Peripheral Vision
Time frame: Baseline, Weeks 28, 52, 76, 100
Change From Baseline in Patient Reported Outcomes Visual Functioning Questionnaire-25 (VFQ-25) Total Scores up to Week 52 and Week 100 - General Health Rating
Time frame: Baseline, Weeks 28, 52, 76, 100
Ocular Adverse Events (AEs) (>=2% in Any Treatment Arm) by Preferred Term for the Study Eye
Time frame: Adverse events were reported from first dose of study treatment until Week 96, plus 30 days post treatment, up to a maximum duration of 100 weeks.
Number of Subjects With Non-ocular Adverse Events (AEs) (>=2% in Any Treatment Arm)
Time frame: Adverse events were reported from first dose of study treatment until Week 96, plus 30 days post treatment, up to a maximum duration of 100 weeks.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- A Plain Language Trial Summary is available on novctrd.comLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
116 sites in 14 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Brolucizumab and Aflibercept in people with Diabetic Macular Edema, run by Novartis Pharmaceuticals at 116 sites in 14 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 3 inclusion and 7 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 30 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 116 sites in United States, Japan, Australia, Israel, Portugal and 9 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 28 Oct 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 Best-corrected Visual Acuity (BCVA) at Week 52 (time frame: Baseline, Week 52). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Jan 2023.