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Branch Retinal Vein OcclusionPhase 3RAPTORNCT03802630

Assessing the Efficacy and Safety of Brolucizumab Versus Aflibercept in Patients With Visual Impairment Due to Macular Edema Secondary to Branch Retinal Vein Occlusion

A Phase 3 study testing Brolucizumab 6 mg and Aflibercept 2 mg in people with Branch Retinal Vein Occlusion, run by Novartis Pharmaceuticals at 102 sites in 19 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

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 branch retinal vein occlusion (BRVO). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Branch 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
450 participants
Where
102 sitesin 19 countries
Study dates
2 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 BRVO 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 BRVO, retinal detachment, macular hole, or choroidal neovascularization of any cause, diabetic retinopathy (except mild non-proliferative) and diabetic macular edema). Hemiretinal vein occlusion should be excluded.
  • 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

102 sites in 19 countries.

102 sites in 19 countries

United States26 sites

  • Novartis Investigative Site

    Abilene, Texas, 79606

  • Novartis Investigative Site

    Arlington, Texas, 76012

  • Novartis Investigative Site

    Asheville, North Carolina, 28803

  • 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

    Colorado Springs, Colorado, 80909

  • Novartis Investigative Site

    Houston, Texas, 77025

  • Novartis Investigative Site

    Houston, Texas, 77030

  • Novartis Investigative Site

    Indianapolis, Indiana, 46280

  • Novartis Investigative Site

    Leawood, Kansas, 66211

  • Novartis Investigative Site

    Lenexa, Kansas, 66215

  • Novartis Investigative Site

    Madison, Wisconsin, 53705-3611

  • Novartis Investigative Site

    Monroeville, Pennsylvania, 15146

  • Novartis Investigative Site

    Mountain View, California, 94040

  • Novartis Investigative Site

    New Albany, Indiana, 47150

  • Novartis Investigative Site

    Pensacola, Florida, 32503

  • 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

Other trials in United States

China11 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

    Shanghai, 200080

  • 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

Other trials in China

Germany10 sites

  • Novartis Investigative Site

    Bonn, 53105

  • Novartis Investigative Site

    Düsseldorf, 40212

  • Novartis Investigative Site

    Freiburg im Breisgau, 79106

  • Novartis Investigative Site

    Göttingen, 37075

  • Novartis Investigative Site

    Leipzig, 04103

  • Novartis Investigative Site

    Ludwigshafen, 67063

  • Novartis Investigative Site

    Mainz, 55131

  • Novartis Investigative Site

    Münster, 48145

  • Novartis Investigative Site

    Regensburg, Bavaria, 93053

  • Novartis Investigative Site

    Ulm, 89075

Other trials in Germany

France8 sites

  • Novartis Investigative Site

    Bordeaux, 33000

  • Novartis Investigative Site

    Créteil, 94000

  • Novartis Investigative Site

    Dijon, 21034

  • Novartis Investigative Site

    Marseille, F 13008

  • Novartis Investigative Site

    Paris, 75010

  • Novartis Investigative Site

    Paris, 75015

  • Novartis Investigative Site

    Saint-Cyr-sur-Loire, Indre Et Loire, 37540

  • Novartis Investigative Site

    Strasbourg, Bas Rhin, 67000

Other trials in France

Japan6 sites

  • Novartis Investigative Site

    Amagasaki, Hyōgo, 660 8550

  • Novartis Investigative Site

    Chiyoda-ku, Tokyo, 101-8309

  • Novartis Investigative Site

    Ishioka, Ibaraki, 315-0037

  • Novartis Investigative Site

    Nagoya, Aichi-ken, 467-8602

  • Novartis Investigative Site

    Osaka, 543-0027

  • Novartis Investigative Site

    Taito-ku, Tokyo, 111-0051

Other trials in Japan

Canada5 sites

  • Novartis Investigative Site

    Calgary, Alberta, T2H0C8

  • Novartis Investigative Site

    London, Ontario, N6A 4V2

  • Novartis Investigative Site

    Ottawa, Ontario, K1Z 8R2

  • Novartis Investigative Site

    Québec, G1S 4L8

  • Novartis Investigative Site

    Toronto, Ontario, M5T 2S8

Other trials in Canada

Italy5 sites

  • Novartis Investigative Site

    Catania, CT, 95123

  • Novartis Investigative Site

    Pisa, PI, 56124

  • Novartis Investigative Site

    Roma, RM, 00133

  • Novartis Investigative Site

    Roma, RM, 00198

  • Novartis Investigative Site

    Udine, UD, 33100

Other trials in Italy

Spain5 sites

  • Novartis Investigative Site

    Barcelona, 08021

  • Novartis Investigative Site

    Madrid, 28040

  • Novartis Investigative Site

    Sant Cugat del Vallès, Catalonia, 08190

  • Novartis Investigative Site

    Santiago de Compostela, Galicia, 15706

  • Novartis Investigative Site

    Seville, Andalusia, 41009

Other trials in Spain

United Kingdom5 sites

  • Novartis Investigative Site

    Birmingham, B18 7QH

  • Novartis Investigative Site

    Bradford, West Yorkshire, BD9 6RJ

  • Novartis Investigative Site

    Liverpool, L7 8XP

  • Novartis Investigative Site

    London, NW3 2QG

  • Novartis Investigative Site

    Westcliff-on-Sea, Essex, SS0 0RY

Other trials in United Kingdom

Russia4 sites

  • Novartis Investigative Site

    Cheboksary, 428028

  • Novartis Investigative Site

    Moscow, 119021

  • Novartis Investigative Site

    Saratov, 410012

  • Novartis Investigative Site

    Sterlitamak, 453128

Other trials in Russia

Czechia3 sites

  • Novartis Investigative Site

    Pardubice, 532 03

  • Novartis Investigative Site

    Prague, 100 34

  • Novartis Investigative Site

    Prague, 12808

Other trials in Czechia

Israel3 sites

  • Novartis Investigative Site

    Jerusalem, 91031

  • Novartis Investigative Site

    Petah Tikva, 4941492

  • Novartis Investigative Site

    Tsrifin, 6093000

Other trials in Israel

Slovakia3 sites

  • Novartis Investigative Site

    Bratislava, 85107

  • Novartis Investigative Site

    Nitra, 950 01

  • Novartis Investigative Site

    Zvolen, 960 01

Other trials in Slovakia

Switzerland2 sites

  • Novartis Investigative Site

    Binningen, 4102

  • Novartis Investigative Site

    Lausanne, Canton of Vaud, 1006

Other trials in Switzerland

Taiwan2 sites

  • Novartis Investigative Site

    Changhua, 50006

  • Novartis Investigative Site

    Taipei, 10002

Other trials in Taiwan

Austria1 site

  • Novartis Investigative Site

    Graz, A-8036

Other trials in Austria

Denmark1 site

  • Novartis Investigative Site

    Copenhagen, 2100

Other trials in Denmark

Hong Kong1 site

  • Novartis Investigative Site

    Hong Kong

Other trials in Hong Kong

Puerto Rico1 site

  • Novartis Investigative Site

    Arecibo, 00612

Other trials in Puerto Rico

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 Branch 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 branch retinal vein occlusion (BRVO).

Read the detailed description

The study was comprised of a 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.

Being tested
Brolucizumab 6 mg, Aflibercept 2 mg, Sham injection
Keywords
Visual impairment, Macular edema, Branch retinal vein occlusion, BRVO, 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 purposes.

    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 groups in NCT03802630
Study groupRoleWhat they receive
Brolucizumab 6 mgExperimental1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individualized flexible treatment (IFT)
Receives: Drug: Brolucizumab 6 mg; Other: Sham injection
Aflibercept 2 mgActive comparator1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individualized 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.

  1. 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)

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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 baseline up to Week 76

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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.

  1. First posted14 Jan 2019
  2. Study start2 Jul 2019
  3. Primary completion26 Jul 2021
  4. Study completion26 Jul 2021

Why it stopped: Study was terminated by sponsor due to increased incidences of AEs of special interest (intraocular inflammation including retinal vasculitis and retinal vascular occlusion), in patients dosed brolucizumab 6mg every 4 weeks beyond 3 initial doses

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
450 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03802630
Sponsor's protocol ID
CRTH258C2301
Other IDs
2018-001842-33, 2018
Acronym
RAPTOR
Status last verified
Jan 2023
First submitted
10 Jan 2019
Last updated
30 Jan 2023
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

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 Branch Retinal Vein Occlusion, run by Novartis Pharmaceuticals at 102 sites in 19 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 102 sites in United States, China, Germany, France, Japan and 14 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 Jul 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?

On the ClinicalTrials.gov record for NCT03802630.

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.

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