Central Retinal Vein OcclusionPhase 3RAVENNCT03810313
Assessing the Efficacy and Safety of Brolucizumab Versus Aflibercept in Patients With Visual Impairment Due to Macular Edema Secondary to Central Retinal Vein Occlusion
A Phase 3 study testing Brolucizumab 6 mg and Aflibercept 2 mg in people with Central Retinal Vein Occlusion, run by Novartis Pharmaceuticals at 120 sites in 20 countries.
Trial summary
The purpose of this study was to evaluate the efficacy and safety of brolucizumab in treatment of patients with macular edema (ME) secondary to central retinal vein occlusion (CRVO). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Central Retinal Vein Occlusion
- What is being tested?
- Brolucizumab 6 mg and Aflibercept 2 mg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 493 participants
- Where
- 120 sitesin 20 countries
- Study dates
- 3 Jul 2019to 26 Jul 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
- Signed informed consent must be obtained prior to participation in the study.
- Patients with visual impairment due to ME secondary to CRVO diagnosed < 6 months prior to screening.
- BCVA score between 78 and 23 letters, inclusive, using ETDRS visual acuity testing charts (approximate Snellen equivalent of 20/32 to 20/320) at both screening and baseline visits.
Who cannot join
- Concomitant conditions or ocular disorders in the study eye at screening or baseline which could, in the opinion of the investigator, prevent response to study treatment or may confound interpretation of study results, compromise visual acuity or require medical or surgical intervention during the first 12-month study period (e.g. structural damage of the fovea, vitreous hemorrhage, retinal vascular occlusion other than CRVO, retinal detachment, macular hole, or choroidal neovascularization of any cause, diabetic retinopathy (except mild non-proliferative) and diabetic macular edema).
- Any active intraocular or periocular infection or active intraocular inflammation (e.g. infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis, uveitis) in study eye at screening or baseline
- Uncontrolled glaucoma in the study eye defined as intraocular pressure (IOP) > 25 mmHg on medication, or according to investigator's judgment, at screening or baseline
- Presence of amblyopia, amaurosis or ocular disorders in the fellow eye with BCVA < 20/200 at screening (except when due to conditions whose surgery may improve VA, e.g. cataract)
- Previous treatment with any anti-VEGF therapy or investigational drugs in the study eye at any time prior to baseline
- Previous use of intraocular or periocular steroids in study eye at any time prior to baseline
Show all 10Show fewer
- Macular laser photocoagulation (focal/grid) in the study eye at any time prior to baseline and peripheral laser photocoagulation in the study eye within 3 months prior to the baseline
- Intraocular surgery in the study eye during the 3-month period prior to baseline
- Vitreoretinal surgery in the study eye at any time prior to baseline
- Aphakia with the absence of posterior capsule in the study eye
Trial locations and contacts
120 sites in 20 countries.
120 sites in 20 countries
United States30 sites
Novartis Investigative Site
Abilene, Texas, 79606
Novartis Investigative Site
Arlington, Texas, 76012
Novartis Investigative Site
Austin, Texas, 78731
Novartis Investigative Site
Austin, Texas, 78750
Novartis Investigative Site
Bellaire, Texas, 77401
Novartis Investigative Site
Bloomfield, New Jersey, 07003
Novartis Investigative Site
Charlotte, North Carolina, 28210
Novartis Investigative Site
Cleveland, Ohio, 44122
Novartis Investigative Site
Cleveland, Ohio, 44195
Novartis Investigative Site
Colorado Springs, Colorado, 80909
Novartis Investigative Site
Fort Myers, Florida, 33912-7125
Novartis Investigative Site
Houston, Texas, 77025
Novartis Investigative Site
Houston, Texas, 77030
Novartis Investigative Site
Indianapolis, Indiana, 46280
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
Minneapolis, Minnesota, 55435
Novartis Investigative Site
Monroeville, Pennsylvania, 15146
Novartis Investigative Site
Mountain View, California, 94040
Novartis Investigative Site
Nashville, Tennessee, 37203
Novartis Investigative Site
New Albany, Indiana, 47150
Novartis Investigative Site
Phoenix, Arizona, 85020
Novartis Investigative Site
Reno, Nevada, 89502
Novartis Investigative Site
San Antonio, Texas, 78240
Novartis Investigative Site
Santa Barbara, California, 93103
Novartis Investigative Site
St. Petersburg, Florida, 33711
Novartis Investigative Site
Stoneham, Massachusetts, 02180
China13 sites
Novartis Investigative Site
Beijing, 100044
Novartis Investigative Site
Beijing, 100730
Novartis Investigative Site
Chengdu, Sichuan, 610041
Novartis Investigative Site
Chongqing, 400038
Novartis Investigative Site
Guangzhou, Guangdong, 510060
Novartis Investigative Site
Harbin, Heilongjiang, 150001
Novartis Investigative Site
Shanghai, 200080
Novartis Investigative Site
Shantou, Guangdong, 515041
Novartis Investigative Site
Tianjin, Tianjin Municipality, 300020
Novartis Investigative Site
Tianjin, Tianjin Municipality, 300070
Novartis Investigative Site
Wenzhou, Zhejiang, 325027
Novartis Investigative Site
Wuhan, Hubei, 430070
Novartis Investigative Site
Wuxi, Jiangsu, 214002
Germany10 sites
Novartis Investigative Site
Düsseldorf, 40225
Novartis Investigative Site
Freiburg im Breisgau, 79106
Novartis Investigative Site
Göttingen, 37075
Novartis Investigative Site
Hanover, 30625
Novartis Investigative Site
Heidelberg, 69120
Novartis Investigative Site
Leipzig, 04103
Novartis Investigative Site
Mainz, 55131
Novartis Investigative Site
Münster, 48145
Novartis Investigative Site
Regensburg, Bavaria, 93053
Novartis Investigative Site
Ulm, 89075
Japan9 sites
Novartis Investigative Site
Chiyoda-ku, Tokyo, 101-8309
Novartis Investigative Site
Hachiōji, Tokyo, 193-0944
Novartis Investigative Site
Kita-gun, Kagawa-ken, 761-0793
Novartis Investigative Site
Kōriyama, Fukushima, 963-8052
Novartis Investigative Site
Matsumoto, Nagano, 390-8621
Novartis Investigative Site
Nagakute, Aichi-ken, 480-1195
Novartis Investigative Site
Nagasaki, Nagasaki, 852-8501
Novartis Investigative Site
Taito-ku, Tokyo, 111-0051
Novartis Investigative Site
Tsu, Mie-ken, 514-8507
Australia7 sites
Novartis Investigative Site
Albury, New South Wales, 2640
Novartis Investigative Site
Hobart, Tasmania, 7000
Novartis Investigative Site
Melbourne, Victoria, 3002
Novartis Investigative Site
Nedlands, Western Australia, 6009
Novartis Investigative Site
Parramatta, New South Wales, 2150
Novartis Investigative Site
Strathfield, New South Wales, 2135
Novartis Investigative Site
Sydney, New South Wales, 2000
Spain6 sites
Novartis Investigative Site
Barcelona, 08025
Novartis Investigative Site
Barcelona, 8022
Novartis Investigative Site
Donostia / San Sebastian, Basque Country, 20080
Novartis Investigative Site
Madrid, 28046
Novartis Investigative Site
Valencia, 46004
Novartis Investigative Site
Zaragoza, 50009
Canada5 sites
Novartis Investigative Site
Calgary, Alberta, T2H0C8
Novartis Investigative Site
London, Ontario, N6A 4V2
Novartis Investigative Site
Ottawa, Ontario, K1H 8L6
Novartis Investigative Site
Ottawa, Ontario, K1Z 8R2
Novartis Investigative Site
Québec, G1S 4L8
France5 sites
Novartis Investigative Site
Créteil, 94000
Novartis Investigative Site
Dijon, 21034
Novartis Investigative Site
Nantes, 44000
Novartis Investigative Site
Paris, 75010
Novartis Investigative Site
Paris, 75940
United Kingdom5 sites
Novartis Investigative Site
Bury Saint Edmonds, Suffolk, IP33 2QZ
Novartis Investigative Site
Leeds, LS9 7TF
Novartis Investigative Site
Liverpool, L7 8XP
Novartis Investigative Site
London, EC1V 2PD
Novartis Investigative Site
Newcastle upon Tyne, NE1 4LP
Czechia4 sites
Novartis Investigative Site
Hradec Králové, CZE, 500 05
Novartis Investigative Site
Pardubice, 532 03
Novartis Investigative Site
Prague, 100 34
Novartis Investigative Site
Prague, 12808
Hungary4 sites
Novartis Investigative Site
Budapest, 1083
Novartis Investigative Site
Debrecen, 4012
Novartis Investigative Site
Pécs, Baranya, 7621
Novartis Investigative Site
Szeged, H 6725
Israel4 sites
Novartis Investigative Site
Jerusalem, 9112001
Novartis Investigative Site
Petah Tikva, 4941492
Novartis Investigative Site
Rehovot, 7610001
Novartis Investigative Site
Tel Aviv, 6423906
Italy4 sites
Novartis Investigative Site
Bari, BA, 70124
Novartis Investigative Site
Milan, MI, 20100
Novartis Investigative Site
Milan, MI, 20122
Novartis Investigative Site
Milan, MI, 20132
Russia4 sites
Novartis Investigative Site
Cheboksary, 428028
Novartis Investigative Site
Kazan', 420066
Novartis Investigative Site
Saint Petersburg, 197022
Novartis Investigative Site
Yekaterinburg, 620109
Thailand3 sites
Novartis Investigative Site
Bangkok, 10330
Novartis Investigative Site
Khon Kaen, THA, 40002
Novartis Investigative Site
Songkhla, Hat Yai, 90110
Greece2 sites
Novartis Investigative Site
Heraklion Crete, Greece, 711 10
Novartis Investigative Site
Larissa, GR, 411 10
Malaysia2 sites
Novartis Investigative Site
Batu Caves, Selangor, 68100
Novartis Investigative Site
Shah Alam, Selangor, 40000
About this study
Official title: An Eighteen-Month, Two-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 Macular Edema Secondary to Central Retinal Vein Occlusion
The purpose of this study was to evaluate the efficacy and safety of brolucizumab in treatment of patients with macular edema (ME) secondary to central retinal vein occlusion (CRVO).
Read the detailed description
The study included Screening Period (Day -28 to Day -1), double-masked treatment period (Day 1 to Week 72), and post-treatment follow-up period (Week 72 to Week 76). Treatment visits were scheduled in 4-week intervals. After 6 initial monthly injections of brolucizumab or aflibercept (loading phase), subjects entered a one-year individualized flexible treatment (IFT) phase. During the IFT phase, an assessment of disease stability was performed at each monthly visit and subjects received either an active or a sham injection. Treatment with active was interrupted when disease stability was reached.
- Conditions
- Central Retinal Vein Occlusion
- Being tested
- Brolucizumab 6 mg, Aflibercept 2 mg, Sham injection
- Keywords
- Visual impairment, Macular edema, Central retinal vein occlusion, CRVO, Brolucizumab, Aflibercept, Vascular endothelial growth factor, VEGF, anti-VEGF
- Medical subject headings
- Retinal Vein Occlusion, Vision Disorders, Macular Edema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Brolucizumab 6 mgDrug
Also called RTH258, ESBA1008
Solution for injection (intravitreal use)
Aflibercept 2 mgDrug
Also called EYLEA®
Solution for injection (Intravitreal use)
Sham injectionOther
Empty sterile syringe without a needle administered as a sham injection for masking. From Week 24 to Week 72 inclusive, a sham treatment was performed to maintain subject masking in case treatment with brolucizumab or aflibercept was not deemed necessary by the investigator.
| Study group | Role | What they receive |
|---|---|---|
| Brolucizumab 6 mg | Experimental | 1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individual flexible treatment (IFT) Receives: Drug: Brolucizumab 6 mg; Other: Sham injection |
| Aflibercept 2 mg | Active comparator | 1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individual flexible treatment (IFT) Receives: Drug: Aflibercept 2 mg; Other: Sham injection |
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 24
BCVA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at an initial testing distance of 4 meters.
Min and max possible scores are 0-100 letters read respectively. A higher score represents better visual functioning.
Missing and censored BCVA values were imputed by Last observation carried forward (LOCF) as the primary approach. Observed values from both scheduled and unscheduled post-baseline visits were used for the LOCF imputation. For subjects with no post-baseline BCVA value, the baseline value was carried forward.
Measured: Baseline, Week 24
Secondary outcomes (15)
Change From Baseline in BCVA Averaged Over Week 40 to Week 52
An average BCVA over week 40 to week 52 was calculated. BCVA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at an initial testing distance of 4 meters.
Min and max possible scores are 0-100 letters read respectively. A higher score represents better visual functioning.
Measured: Baseline, Week 40 to Week 52
Change From Baseline in BCVA Averaged Over Week 64 to Week 76
An average BCVA over week 64 to week 76 was calculated. BCVA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at an initial testing distance of 4 meters.
Min and max possible scores are 0-100 letters read respectively. A higher score represents better visual functioning.
Measured: Baseline, Week 64 to Week 76
Change From Baseline in BCVA by Visit up to Week 76
BCVA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at an initial testing distance of 4 meters. Min and max possible scores are 0-100 letters read respectively. A higher score represents better visual functioning.
Measured: Baseline and every 4 weeks from baseline up to Week 76
Proportion of Participants With a Gain ≥ 5, 10 and 15 Letters in BCVA by Visit Compared to Baseline
The summary by visit was conducted based on the BCVA observed from each of the corresponding visits.
BCVA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at an initial testing distance of 4 meters.
Min and max possible scores are 0-100 letters read respectively. A higher score represents better visual functioning.
Every 5 letters represents 1 line of vision on the reading chart.
Measured: Baseline and every 4 weeks from baseline up to Week 76
Proportion of Participants With a Loss ≥ 5, 10 and 15 Letters in BCVA by Visit Compared to Baseline
The summary by visit was conducted based on the BCVA observed from each of the corresponding visit.
BCVA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at an initial testing distance of 4 meters.
Min and max possible scores are 0-100 letters read respectively. A higher score represents better visual functioning.
Every 5 letters represents 1 line of vision on the reading chart.
Measured: Baseline and every 4 weeks from baseline up to Week 76
Change From Baseline in CSFT Averaged Over Week 40 to Week 52
Change from baseline in central subfield thickness (CSFT) averaged over Week 40 to Week 52, measured in μm by Spectral Domain Optical Coherence Tomography (SD-OCT)
Measured: Baseline, Week 40 to Week 52
Change From Baseline in CSFT Averaged Over Week 64 to Week 76
Change from baseline in central subfield thickness (CSFT) averaged over Week 64 to Week 76, measured in μm by Spectral Domain Optical Coherence Tomography (SD-OCT)
Measured: Baseline, Week 64 to Week 76
Change From Baseline in CSFT by Visit up to Week 76
Change from baseline in central subfield thickness (CSFT) measured in μm by Spectral Domain Optical Coherence Tomography (SD-OCT)
Measured: Baseline, and every 4 weeks from baseline up to Week 76
Proportion of Subjects With Presence of Retinal Fluid (Intra- and/or Subretinal Fluid) in the Study Eye by Visit up to Week 76
Presence of retinal fluid (intra- and/or subretinal fluid) assessed by Spectral Domain Optical Coherence Tomography (SD-OCT)
Measured: Every 4 weeks from week 4 up to Week 76
Proportion of Subjects With a CSFT < 300 μm for the Study Eye by Visit up to Week 76
Central subfield thickness (CSFT) is measured in μm by Spectral Domain Optical Coherence Tomography (SD-OCT)
Measured: Every 4 weeks from week 4 up to Week 76
Number of Injections Between Week 24 and Week 52 and Between Week 24 and Week 72
Number of administered injections during the individualized flexible treatment (IFT) period, between Week 24 and Week 52 and between Week 24 and Week 72 are presented
Measured: Week 24 to Week 52 and Week 24 to Week 72
Time to Recurrence After Week 20 and up to Week 76
Recurrence is defined as the need for injection while showing a lack of disease stability for the first time after Week 20 and up to Week 76.
For subjects with recurrence after the Week 20 visit, time-to-event is calculated as (first time with the lack of disease stability - the injection date on Week 20 visit + 1). For subjects without recurrence after Week 20, the censoring time will be calculated as (last visit with disease stability assessment - the injection date on Week 20 visit + 1).
Measured: Week 20 to Week 76
Number of Subjects With Ocular and Non-ocular AEs up to Week 52 and Week 76
Number of subjects with at least one ocular or non-ocular Adverse Events (AEs).
Measured: Baseline to Week 76
Change From Baseline in Patient Reported Outcomes (NEI VFQ-25) at Week 24, Week 52 and Week 76
The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) measures a patient's subjective assessment of vision-related Quality of Life (QoL).
The 11 subscales in the VFQ-25 are general vision, ocular pain, near activities, distance activities, social functioning, mental health, role difficulties, dependency, driving, color vision, and peripheral vision. The scores on the subscales were added together for a total score, which ranged from 0 to 100. A higher score indicated better vision-related quality of life.
Measured: Baseline, Week 24, Week 52 and Week 76
Number of Subjects According to Their Anti-drug Antibody (ADA) Titer at Screening and Week 4, Week 12, Week 24, Week 36, Week 52 and Week 76
Anti-drug antibodies (ADA) levels were assessed from subjects assigned to brolucizumab treatment only.
Measured: Baseline, Week 4, Week 12, Week 24, Week 36, Week 52 and Week 76
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2019
- Study start3 Jul 2019
- Primary completion26 Jul 2021
- Study completion26 Jul 2021
Why it stopped: Study was terminated by sponsor due to increased incidences of adverse events of special interest (intraocular inflammation including retinal vasculitis, and retinal vascular occlusion), in patients dosed every 4 weeks beyond 3 initial doses.
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 Central Retinal Vein OcclusionStudies 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
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 493 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
- NCT03810313
- Sponsor's protocol ID
- CRTH258C2302
- Other IDs
- 2018-001788-21, 2018
- Acronym
- RAVEN
- Status last verified
- Jan 2023
- First submitted
- 17 Jan 2019
- Last updated
- 30 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- 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
- An Eighteen-Month, Two-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 Macular Edema Secondary to Central Retinal Vein Occlusion
- ClinicalTrials.gov ID
- NCT03810313
- Acronym / sponsor ID
- RAVEN / CRTH258C2302
- Conditions
- Central Retinal Vein Occlusion
- Keywords
- Visual impairment, Macular edema, Central retinal vein occlusion, CRVO, Brolucizumab, Aflibercept, Vascular endothelial growth factor, VEGF
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was terminated by sponsor due to increased incidences of adverse events of special interest (intraocular inflammation including retinal vasculitis, and retinal vascular occlusion), in patients dosed every 4 weeks beyond 3 initial doses.
- Enrolment
- 493 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 3 Jul 2019 (actual)
- Primary completion
- 26 Jul 2021 (actual)
- Study completion
- 26 Jul 2021 (actual)
- First posted
- 18 Jan 2019 (actual)
- Results
- Posted 8 Aug 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 macular edema (ME) secondary to central retinal vein occlusion (CRVO).
Detailed description
The study included Screening Period (Day -28 to Day -1), double-masked treatment period (Day 1 to Week 72), and post-treatment follow-up period (Week 72 to Week 76). Treatment visits were scheduled in 4-week intervals. After 6 initial monthly injections of brolucizumab or aflibercept (loading phase), subjects entered a one-year individualized flexible treatment (IFT) phase. During the IFT phase, an assessment of disease stability was performed at each monthly visit and subjects received either an active or a sham injection. Treatment with active was interrupted when disease stability was reached.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Brolucizumab 6 mg | Experimental | Drug: Brolucizumab 6 mg, Other: Sham injection1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individual flexible treatment (IFT) |
| Aflibercept 2 mg | Active comparator | Drug: Aflibercept 2 mg, Other: Sham injection1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individual flexible treatment (IFT) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Signed informed consent must be obtained prior to participation in the study.
- Patients with visual impairment due to ME secondary to CRVO diagnosed < 6 months prior to screening.
- BCVA score between 78 and 23 letters, inclusive, using ETDRS visual acuity testing charts (approximate Snellen equivalent of 20/32 to 20/320) at both screening and baseline visits.
Key exclusion criteria (10 listed)
- Concomitant conditions or ocular disorders in the study eye at screening or baseline which could, in the opinion of the investigator, prevent response to study treatment or may confound interpretation of study results, compromise visual acuity or require medical or surgical intervention during the first 12-month study period (e.g. structural damage of the fovea, vitreous hemorrhage, retinal vascular occlusion other than CRVO, retinal detachment, macular hole, or choroidal neovascularization of any cause, diabetic retinopathy (except mild non-proliferative) and diabetic macular edema).
- Any active intraocular or periocular infection or active intraocular inflammation (e.g. infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis, uveitis) in study eye at screening or baseline
- Uncontrolled glaucoma in the study eye defined as intraocular pressure (IOP) > 25 mmHg on medication, or according to investigator's judgment, at screening or baseline
- Presence of amblyopia, amaurosis or ocular disorders in the fellow eye with BCVA < 20/200 at screening (except when due to conditions whose surgery may improve VA, e.g. cataract)
- Previous treatment with any anti-VEGF therapy or investigational drugs in the study eye at any time 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 |
|---|---|---|
| Brolucizumab 6 mgAlso: RTH258, ESBA1008Solution for injection (intravitreal use) | Drug | Brolucizumab 6 mg |
| Aflibercept 2 mgAlso: EYLEA®Solution for injection (Intravitreal use) | Drug | Aflibercept 2 mg |
| Sham injectionEmpty sterile syringe without a needle administered as a sham injection for masking. From Week 24 to Week 72 inclusive, a sham treatment was performed to maintain subject masking in case treatment with brolucizumab or aflibercept was not deemed necessary by the investigator. | Other | Aflibercept 2 mg, Brolucizumab 6 mg |
Primary outcome
Change From Baseline in Best-corrected Visual Acuity (BCVA) at Week 24
Time frame: Baseline, Week 24
BCVA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at an initial testing distance of 4 meters. Min and max possible scores are 0-100 letters read respectively. A higher score represents better visual functioning. Missing and censored BCVA values were imputed by Last observation carried forward (LOCF) as the primary approach. Observed values from both scheduled and unscheduled post-baseline visits were used for the LOCF imputation. For subjects with no post-baseline BCVA value, the baseline value was carried forward.
15 secondary outcomes
Change From Baseline in BCVA Averaged Over Week 40 to Week 52
Time frame: Baseline, Week 40 to Week 52
Change From Baseline in BCVA Averaged Over Week 64 to Week 76
Time frame: Baseline, Week 64 to Week 76
Change From Baseline in BCVA by Visit up to Week 76
Time frame: Baseline and every 4 weeks from baseline up to Week 76
Proportion of Participants With a Gain ≥ 5, 10 and 15 Letters in BCVA by Visit Compared to Baseline
Time frame: Baseline and every 4 weeks from baseline up to Week 76
Proportion of Participants With a Loss ≥ 5, 10 and 15 Letters in BCVA by Visit Compared to Baseline
Time frame: Baseline and every 4 weeks from baseline up to Week 76
Change From Baseline in CSFT Averaged Over Week 40 to Week 52
Time frame: Baseline, Week 40 to Week 52
Change From Baseline in CSFT Averaged Over Week 64 to Week 76
Time frame: Baseline, Week 64 to Week 76
Change From Baseline in CSFT by Visit up to Week 76
Time frame: Baseline, and every 4 weeks from baseline up to Week 76
Proportion of Subjects With Presence of Retinal Fluid (Intra- and/or Subretinal Fluid) in the Study Eye by Visit up to Week 76
Time frame: Every 4 weeks from week 4 up to Week 76
Proportion of Subjects With a CSFT < 300 μm for the Study Eye by Visit up to Week 76
Time frame: Every 4 weeks from week 4 up to Week 76
Number of Injections Between Week 24 and Week 52 and Between Week 24 and Week 72
Time frame: Week 24 to Week 52 and Week 24 to Week 72
Time to Recurrence After Week 20 and up to Week 76
Time frame: Week 20 to Week 76
Number of Subjects With Ocular and Non-ocular AEs up to Week 52 and Week 76
Time frame: Baseline to Week 76
Change From Baseline in Patient Reported Outcomes (NEI VFQ-25) at Week 24, Week 52 and Week 76
Time frame: Baseline, Week 24, Week 52 and Week 76
Number of Subjects According to Their Anti-drug Antibody (ADA) Titer at Screening and Week 4, Week 12, Week 24, Week 36, Week 52 and Week 76
Time frame: Baseline, Week 4, Week 12, Week 24, Week 36, Week 52 and Week 76
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.
- Results for CRTH258C2302 from the Novartis Clinical Trials WebsiteLink provided by the sponsor.
- 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
120 sites in 20 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Brolucizumab 6 mg and Aflibercept 2 mg in people with Central Retinal Vein Occlusion, run by Novartis Pharmaceuticals at 120 sites in 20 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 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: stopped early, 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 120 sites in United States, China, Germany, Japan, Australia and 15 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 8 Aug 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 24 (time frame: Baseline, Week 24). 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.