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

NCT03802630 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: CRTH258C23012018-001842-33
• Study Type: interventional
• Target: 450
• Locations: 19 countries
• Sites: 102

Brief 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).

Conditions

Branch Retinal Vein Occlusion

Keywords

Visual impairment; Macular edema; Branch retinal vein occlusion; BRVO; Brolucizumab; Aflibercept; Vascular endothelial growth factor; VEGF; anti-VEGF

Outcome Measures

Primary Outcomes (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.

  Baseline, Week 24

Secondary Outcomes (15)

• Change From Baseline in BCVA Averaged Over Week 40 to Week 52

  Baseline, Week 40 to Week 52

• Change From Baseline in BCVA Averaged Over Week 64 to Week 76

  Baseline, Week 64 to Week 76

• Change From Baseline in BCVA by Visit up to Week 76

  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

  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

  Baseline and every 4 weeks from baseline up to Week 76

Study Arms (2)

Brolucizumab 6 mg

EXPERIMENTAL

1 intravitreal injection every 4 weeks for a total of 6 injections, followed by 48 weeks of individualized flexible treatment (IFT)

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 individualized flexible treatment (IFT)

Drug: Aflibercept 2 mg; Other: Sham injection

Interventions

Brolucizumab 6 mg DRUG

Solution for injection (intravitreal use)

Also known as: RTH258, ESBA1008

Brolucizumab 6 mg

Aflibercept 2 mg DRUG

Solution for injection (Intravitreal use)

Also known as: EYLEA®

Aflibercept 2 mg

Sham injection OTHER

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.

Aflibercept 2 mg; Brolucizumab 6 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (102)

Novartis Investigative Site

Phoenix, Arizona, 85020, United States

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Mountain View, California, 94040, United States

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Santa Barbara, California, 93103, United States

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Colorado Springs, Colorado, 80909, United States

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Pensacola, Florida, 32503, United States

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St. Petersburg, Florida, 33711, United States

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Indianapolis, Indiana, 46280, United States

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New Albany, Indiana, 47150, United States

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Leawood, Kansas, 66211, United States

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Lenexa, Kansas, 66215, United States

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Stoneham, Massachusetts, 02180, United States

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Reno, Nevada, 89502, United States

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Bloomfield, New Jersey, 07003, United States

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Asheville, North Carolina, 28803, United States

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Charlotte, North Carolina, 28210, United States

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Cleveland, Ohio, 44122, United States

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Monroeville, Pennsylvania, 15146, United States

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Abilene, Texas, 79606, United States

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Arlington, Texas, 76012, United States

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Austin, Texas, 78731, United States

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Austin, Texas, 78750, United States

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Bellaire, Texas, 77401, United States

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Houston, Texas, 77025, United States

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Houston, Texas, 77030, United States

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San Antonio, Texas, 78240, United States

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Madison, Wisconsin, 53705-3611, United States

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Graz, A-8036, Austria

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Calgary, Alberta, T2H0C8, Canada

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London, Ontario, N6A 4V2, Canada

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Ottawa, Ontario, K1Z 8R2, Canada

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Toronto, Ontario, M5T 2S8, Canada

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Québec, G1S 4L8, Canada

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Guangzhou, Guangdong, 510060, China

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Wuhan, Hubei, 430070, China

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Wuxi, Jiangsu, 214002, China

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Chengdu, Sichuan, 610041, China

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Tianjin, Tianjin Municipality, 300020, China

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Tianjin, Tianjin Municipality, 300070, China

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Wenzhou, Zhejiang, 325027, China

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Beijing, 100044, China

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Beijing, 100730, China

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Chongqing, 400038, China

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Shanghai, 200080, China

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Pardubice, 532 03, Czechia

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Prague, 100 34, Czechia

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Prague, 12808, Czechia

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Copenhagen, 2100, Denmark

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Strasbourg, Bas Rhin, 67000, France

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

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Bordeaux, 33000, France

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Créteil, 94000, France

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Dijon, 21034, France

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Marseille, F 13008, France

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Paris, 75010, France

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Paris, 75015, France

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Regensburg, Bavaria, 93053, Germany

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Bonn, 53105, Germany

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Düsseldorf, 40212, Germany

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Freiburg im Breisgau, 79106, Germany

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Göttingen, 37075, Germany

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Leipzig, 04103, Germany

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Ludwigshafen, 67063, Germany

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Mainz, 55131, Germany

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Münster, 48145, Germany

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Ulm, 89075, Germany

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Hong Kong, Hong Kong

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Jerusalem, 91031, Israel

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Petah Tikva, 4941492, Israel

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Ẕerifin, 6093000, Israel

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Catania, CT, 95123, Italy

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Pisa, PI, 56124, Italy

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Roma, RM, 00133, Italy

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Roma, RM, 00198, Italy

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Udine, UD, 33100, Italy

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Nagoya, Aichi-ken, 467-8602, Japan

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Amagasaki, Hyōgo, 660 8550, Japan

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Ishioka, Ibaraki, 315-0037, Japan

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Chiyoda-ku, Tokyo, 101-8309, Japan

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Taito-ku, Tokyo, 111-0051, Japan

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Osaka, 543-0027, Japan

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Arecibo, 00612, Puerto Rico

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Cheboksary, 428028, Russia

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Moscow, 119021, Russia

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Saratov, 410012, Russia

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Sterlitamak, 453128, Russia

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Bratislava, 85107, Slovakia

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Nitra, 950 01, Slovakia

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Zvolen, 960 01, Slovakia

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Seville, Andalusia, 41009, Spain

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Sant Cugat del Vallès, Catalonia, 08190, Spain

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Santiago de Compostela, Galicia, 15706, Spain

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Barcelona, 08021, Spain

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Madrid, 28040, Spain

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Lausanne, Canton of Vaud, 1006, Switzerland

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Binningen, 4102, Switzerland

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Changhua, 50006, Taiwan

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Taipei, 10002, Taiwan

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Westcliff-on-Sea, Essex, SS0 0RY, United Kingdom

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Bradford, West Yorkshire, BD9 6RJ, United Kingdom

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Birmingham, B18 7QH, United Kingdom

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Liverpool, L7 8XP, United Kingdom

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London, NW3 2QG, United Kingdom

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Related Links

• Results for CRTH258C2301 from the Novartis Clinical Trials Website
• A Plain Language Trial Summary is available on novctrd.com

MeSH Terms

Conditions

Retinal Vein Occlusion; Vision Disorders; Macular Edema

Interventions

brolucizumab; aflibercept; salicylhydroxamic acid

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases; Venous Thrombosis; Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Macular Degeneration; Retinal Degeneration

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: A masked evaluating investigator was responsible for all aspects of the study except the injections and the safety assessment following the injections. An unmasked treating investigator performed the injections and assessed patient safety following the injections.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2019
• First Posted: January 14, 2019
• Study Start: July 2, 2019
• Primary Completion: July 26, 2021
• Study Completion: July 26, 2021
• Last Updated: January 30, 2023
• Results First Posted: July 28, 2022

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share

Locations

JP (6); CH (2); CN (11); IL (3); RU (4); TW (2); CA (5); CZ (3); SL (3); DE (10); FR (8); HK (1); US (26); IT (5); PR (1); GB (5); DK (1); AU (1); ES (5)