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

NCT03810313 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: CRTH258C23022018-001788-21
• Study Type: interventional
• Target: 493
• Locations: 20 countries
• Sites: 120

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 central retinal vein occlusion (CRVO).

Conditions

Central Retinal Vein Occlusion

Keywords

Visual impairment; Macular edema; Central retinal vein occlusion; CRVO; 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 individual 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 individual 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. 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 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.

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 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
• 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 (120)

Novartis Investigative Site

Phoenix, Arizona, 85020, United States

Location

Novartis Investigative Site

La Jolla, California, 92093, United States

Location

Novartis Investigative Site

Mountain View, California, 94040, United States

Location

Novartis Investigative Site

Santa Barbara, California, 93103, United States

Location

Novartis Investigative Site

Colorado Springs, Colorado, 80909, United States

Location

Novartis Investigative Site

Fort Myers, Florida, 33912-7125, United States

Location

Novartis Investigative Site

St. Petersburg, Florida, 33711, United States

Location

Novartis Investigative Site

Indianapolis, Indiana, 46280, United States

Location

Novartis Investigative Site

New Albany, Indiana, 47150, United States

Location

Novartis Investigative Site

Leawood, Kansas, 66211, United States

Location

Novartis Investigative Site

Lenexa, Kansas, 66215, United States

Location

Novartis Investigative Site

Stoneham, Massachusetts, 02180, United States

Location

Novartis Investigative Site

Minneapolis, Minnesota, 55435, United States

Location

Novartis Investigative Site

Reno, Nevada, 89502, United States

Location

Novartis Investigative Site

Bloomfield, New Jersey, 07003, United States

Location

Novartis Investigative Site

Charlotte, North Carolina, 28210, United States

Location

Novartis Investigative Site

Cleveland, Ohio, 44122, United States

Location

Novartis Investigative Site

Cleveland, Ohio, 44195, United States

Location

Novartis Investigative Site

Monroeville, Pennsylvania, 15146, United States

Location

Novartis Investigative Site

Memphis, Tennessee, 38119, United States

Location

Novartis Investigative Site

Nashville, Tennessee, 37203, United States

Location

Novartis Investigative Site

Abilene, Texas, 79606, United States

Location

Novartis Investigative Site

Arlington, Texas, 76012, United States

Location

Novartis Investigative Site

Austin, Texas, 78731, United States

Location

Novartis Investigative Site

Austin, Texas, 78750, United States

Location

Novartis Investigative Site

Bellaire, Texas, 77401, United States

Location

Novartis Investigative Site

Houston, Texas, 77025, United States

Location

Novartis Investigative Site

Houston, Texas, 77030, United States

Location

Novartis Investigative Site

San Antonio, Texas, 78240, United States

Location

Novartis Investigative Site

Madison, Wisconsin, 53705-3611, United States

Location

Novartis Investigative Site

Albury, New South Wales, 2640, Australia

Location

Novartis Investigative Site

Parramatta, New South Wales, 2150, Australia

Location

Novartis Investigative Site

Strathfield, New South Wales, 2135, Australia

Location

Novartis Investigative Site

Sydney, New South Wales, 2000, Australia

Location

Novartis Investigative Site

Hobart, Tasmania, 7000, Australia

Location

Novartis Investigative Site

Melbourne, Victoria, 3002, Australia

Location

Novartis Investigative Site

Nedlands, Western Australia, 6009, Australia

Location

Novartis Investigative Site

Calgary, Alberta, T2H0C8, Canada

Location

Novartis Investigative Site

London, Ontario, N6A 4V2, Canada

Location

Novartis Investigative Site

Ottawa, Ontario, K1H 8L6, Canada

Location

Novartis Investigative Site

Ottawa, Ontario, K1Z 8R2, Canada

Location

Novartis Investigative Site

Québec, G1S 4L8, Canada

Location

Novartis Investigative Site

Guangzhou, Guangdong, 510060, China

Location

Novartis Investigative Site

Shantou, Guangdong, 515041, China

Location

Novartis Investigative Site

Harbin, Heilongjiang, 150001, China

Location

Novartis Investigative Site

Wuhan, Hubei, 430070, China

Location

Novartis Investigative Site

Wuxi, Jiangsu, 214002, China

Location

Novartis Investigative Site

Chengdu, Sichuan, 610041, China

Location

Novartis Investigative Site

Tianjin, Tianjin Municipality, 300020, China

Location

Novartis Investigative Site

Tianjin, Tianjin Municipality, 300070, China

Location

Novartis Investigative Site

Wenzhou, Zhejiang, 325027, China

Location

Novartis Investigative Site

Beijing, 100044, China

Location

Novartis Investigative Site

Beijing, 100730, China

Location

Novartis Investigative Site

Chongqing, 400038, China

Location

Novartis Investigative Site

Shanghai, 200080, China

Location

Novartis Investigative Site

Hradec Králové, CZE, 500 05, Czechia

Location

Novartis Investigative Site

Pardubice, 532 03, Czechia

Location

Novartis Investigative Site

Prague, 100 34, Czechia

Location

Novartis Investigative Site

Prague, 12808, Czechia

Location

Novartis Investigative Site

Créteil, 94000, France

Location

Novartis Investigative Site

Dijon, 21034, France

Location

Novartis Investigative Site

Nantes, 44000, France

Location

Novartis Investigative Site

Paris, 75010, France

Location

Novartis Investigative Site

Paris, 75940, France

Location

Novartis Investigative Site

Regensburg, Bavaria, 93053, Germany

Location

Novartis Investigative Site

Düsseldorf, 40225, Germany

Location

Novartis Investigative Site

Freiburg im Breisgau, 79106, Germany

Location

Novartis Investigative Site

Göttingen, 37075, Germany

Location

Novartis Investigative Site

Hanover, 30625, Germany

Location

Novartis Investigative Site

Heidelberg, 69120, Germany

Location

Novartis Investigative Site

Leipzig, 04103, Germany

Location

Novartis Investigative Site

Mainz, 55131, Germany

Location

Novartis Investigative Site

Münster, 48145, Germany

Location

Novartis Investigative Site

Ulm, 89075, Germany

Location

Novartis Investigative Site

Heraklion Crete, Greece, 711 10, Greece

Location

Novartis Investigative Site

Larissa, GR, 411 10, Greece

Location

Novartis Investigative Site

Pécs, Baranya, 7621, Hungary

Location

Novartis Investigative Site

Budapest, 1083, Hungary

Location

Novartis Investigative Site

Debrecen, 4012, Hungary

Location

Novartis Investigative Site

Szeged, H 6725, Hungary

Location

Novartis Investigative Site

Jerusalem, 9112001, Israel

Location

Novartis Investigative Site

Petah Tikva, 4941492, Israel

Location

Novartis Investigative Site

Rehovot, 7610001, Israel

Location

Novartis Investigative Site

Tel Aviv, 6423906, Israel

Location

Novartis Investigative Site

Bari, BA, 70124, Italy

Location

Novartis Investigative Site

Milan, MI, 20100, Italy

Location

Novartis Investigative Site

Milan, MI, 20122, Italy

Location

Novartis Investigative Site

Milan, MI, 20132, Italy

Location

Novartis Investigative Site

Nagakute, Aichi-ken, 480-1195, Japan

Location

Novartis Investigative Site

Kōriyama, Fukushima, 963-8052, Japan

Location

Novartis Investigative Site

Kita-gun, Kagawa-ken, 761-0793, Japan

Location

Novartis Investigative Site

Tsu, Mie-ken, 514-8507, Japan

Location

Novartis Investigative Site

Matsumoto, Nagano, 390-8621, Japan

Location

Novartis Investigative Site

Nagasaki, Nagasaki, 852-8501, Japan

Location

Novartis Investigative Site

Chiyoda-ku, Tokyo, 101-8309, Japan

Location

Novartis Investigative Site

Hachiōji, Tokyo, 193-0944, Japan

Location

Novartis Investigative Site

Taito-ku, Tokyo, 111-0051, Japan

Location

Novartis Investigative Site

Batu Caves, Selangor, 68100, Malaysia

Location

Novartis Investigative Site

Shah Alam, Selangor, 40000, Malaysia

Location

Novartis Investigative Site

Tilburg, 5022 GC, Netherlands

Location

Novartis Investigative Site

Arecibo, 00612, Puerto Rico

Location

Novartis Investigative Site

Cheboksary, 428028, Russia

Location

Novartis Investigative Site

Kazan', 420066, Russia

Location

Novartis Investigative Site

Saint Petersburg, 197022, Russia

Location

Novartis Investigative Site

Yekaterinburg, 620109, Russia

Location

Novartis Investigative Site

Donostia / San Sebastian, Basque Country, 20080, Spain

Location

Novartis Investigative Site

Barcelona, 08025, Spain

Location

Novartis Investigative Site

Barcelona, 8022, Spain

Location

Novartis Investigative Site

Madrid, 28046, Spain

Location

Novartis Investigative Site

Valencia, 46004, Spain

Location

Novartis Investigative Site

Zaragoza, 50009, Spain

Location

Novartis Investigative Site

Songkhla, Hat Yai, 90110, Thailand

Location

Novartis Investigative Site

Khon Kaen, THA, 40002, Thailand

Location

Novartis Investigative Site

Bangkok, 10330, Thailand

Location

Novartis Investigative Site

Ankara, 06100, Turkey (Türkiye)

Location

Novartis Investigative Site

Bury Saint Edmonds, Suffolk, IP33 2QZ, United Kingdom

Location

Novartis Investigative Site

Leeds, LS9 7TF, United Kingdom

Location

Novartis Investigative Site

Liverpool, L7 8XP, United Kingdom

Location

Novartis Investigative Site

London, EC1V 2PD, United Kingdom

Location

Novartis Investigative Site

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

Related Links

• Results for CRTH258C2302 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

+ 1 862 778 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 17, 2019
• First Posted: January 18, 2019
• Study Start: July 3, 2019
• Primary Completion: July 26, 2021
• Study Completion: July 26, 2021
• Last Updated: January 30, 2023
• Results First Posted: August 8, 2022

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share

Locations

US (30); PR (1); CZ (4); DE (10); ES (6); TU (1); CN (13); JP (9); MY (2); TH (3); FR (5); HU (4); IL (4); AU (7); GR (2); GB (5); RU (4); NL (1); IT (4); CA (5)