Study of Safety and Efficacy of Brolucizumab 6 mg Dosed Every 4 Weeks Compared to Aflibercept 2 mg Dosed Every 4 Weeks in Patients With Retinal Fluid Despite Frequent Anti-VEGF Injections

NCT03710564 | Terminated Phase 3 Results FDA Drug

• 1 other identifier: CRTH258AUS04
• Study Type: interventional
• Target: 535
• Locations: 2 countries
• Sites: 61

Brief Summary

This clinical study was designed to compare the safety and efficacy of brolucizumab 6 mg dosed every 4 weeks to aflibercept 2 mg dosed every 4 weeks in those neovascular age-related macular degeneration (nAMD) patients with retinal fluid despite frequent anti-Vascular Endothelial Growth Factor (VEGF) injections.

Conditions

Age-Related Macular Degeneration

Keywords

neovascular age-related macular degeneration; nAMD; intravitreal injection; IVT; anti-VEGF; brolucizumab; aflibercept; EYLEA; double-masked; MERLIN; BEOVU

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Best-Corrected Visual Acuity (BCVA) at Week 52

  BCVA was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing protocol at an initial testing distance of 4 meters. BCVA min and max possible scores are 0-100 respectively and a higher score represents better functioning. A positive change from baseline represents better functioning. Baseline BCVA was defined as the last measurement on or prior to the baseline visit. BCVA assessments after start of alternative anti-VEGF treatment in the study eye were censored and imputed by the last value prior to start of alternative treatment. Last observation carried forward (LOCF) was used for the imputation of missing values.

  Baseline, week 52

Secondary Outcomes (16)

• Stable Visual Acuity (VA) or Improvement in VA at Week 52 and Week 104

  Baseline, weeks 52 and 104

• Loss in Best-Corrected Visual Acuity (BCVA) of 5 Letters or More

  Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100 and 104

• Loss in Best-Corrected Visual Acuity (BCVA) of 10 Letters or More

  Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100 and 104

• Loss in Best-Corrected Visual Acuity (BCVA) of 15 Letters or More

  Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100 and 104

• Gain in Best-Corrected Visual Acuity (BCVA) of 5 Letters or More

  Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100 and 104

Study Arms (2)

Brolucizumab

EXPERIMENTAL

Brolucizumab 6 mg dosed every 4 weeks was administered via intravitreal injection for 100 weeks.

Biological: Brolucizumab

Aflibercept

ACTIVE COMPARATOR

Aflibercept 2 mg dosed every 4 weeks was administered via intravitreal injection for 100 weeks.

Biological: Aflibercept

Interventions

Brolucizumab BIOLOGICAL

6 mg/0.05mL solution for intravitreal injection

Also known as: RTH258

Brolucizumab

Aflibercept BIOLOGICAL

2 mg/0.05mL solution for intravitreal injection

Also known as: EYLEA

Aflibercept

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent
• Diagnosis of wet age-related macular degeneration (AMD)
• Currently receiving anti-VEGF injections

You may not qualify if:

• Active infection or inflammation in either eye
• Significant fibrosis in the study eye
• Recent ocular surgery
• Uncontrolled glaucoma
• Use of medications as specified in the protocol
• Pregnant, nursing
• Of child-bearing potential unless using highly effective method of contraception

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (61)

Novartis Investigative Site

Phoenix, Arizona, 85016, United States

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Novartis Investigative Site

Phoenix, Arizona, 85020, United States

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Novartis Investigative Site

Phoenix, Arizona, 85053, United States

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Novartis Investigative Site

Beverly Hills, California, 90211, United States

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Novartis Investigative Site

Huntington Beach, California, 92647, United States

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Novartis Investigative Site

Mountain View, California, 94040, United States

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Novartis Investigative Site

Oakland, California, 94609, United States

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Novartis Investigative Site

Oxnard, California, 93036, United States

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Novartis Investigative Site

Palo Alto, California, 94303, United States

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Novartis Investigative Site

Redlands, California, 92374, United States

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Novartis Investigative Site

Sacramento, California, 95841, United States

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Novartis Investigative Site

San Francisco, California, 94107, United States

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Novartis Investigative Site

Santa Barbara, California, 93103, United States

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Novartis Investigative Site

Colorado Springs, Colorado, 80909, United States

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Novartis Investigative Site

Golden, Colorado, 80401, United States

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Novartis Investigative Site

Deerfield Beach, Florida, 33064, United States

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Novartis Investigative Site

Fort Lauderdale, Florida, 33308, United States

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Novartis Investigative Site

Fort Myers, Florida, 33912-7125, United States

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Novartis Investigative Site

Miami, Florida, 33136, United States

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Novartis Investigative Site

Mt. Dora, Florida, 32757, United States

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Novartis Investigative Site

Pensacola, Florida, 32503, United States

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Novartis Investigative Site

St. Petersburg, Florida, 33711, United States

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Novartis Investigative Site

Stuart, Florida, 34994, United States

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Novartis Investigative Site

Marietta, Georgia, 30060, United States

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Novartis Investigative Site

‘Aiea, Hawaii, 96701, United States

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Novartis Investigative Site

Wheaton, Illinois, 60187, United States

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Novartis Investigative Site

West Des Moines, Iowa, 50266, United States

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Novartis Investigative Site

Lenexa, Kansas, 66215, United States

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Novartis Investigative Site

New Orleans, Louisiana, 70115-8139, United States

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Novartis Investigative Site

West Monroe, Louisiana, 71291, United States

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Novartis Investigative Site

Waldorf, Maryland, 20602, United States

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Novartis Investigative Site

Boston, Massachusetts, 02111, United States

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Novartis Investigative Site

Boston, Massachusetts, 02114, United States

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Novartis Investigative Site

Springfield, Massachusetts, 01107, United States

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Novartis Investigative Site

Royal Oak, Michigan, 48073, United States

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Novartis Investigative Site

St Louis, Missouri, 63110, United States

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Novartis Investigative Site

Las Vegas, Nevada, 89144, United States

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Novartis Investigative Site

Reno, Nevada, 89502, United States

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Novartis Investigative Site

Bloomfield, New Jersey, 07003, United States

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Novartis Investigative Site

Toms River, New Jersey, 08755, United States

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Novartis Investigative Site

Syracuse, New York, 13224, United States

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Novartis Investigative Site

Charlotte, North Carolina, 28210, United States

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Novartis Investigative Site

Cleveland, Ohio, 44122, United States

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Novartis Investigative Site

Fairfield, Ohio, 45014, United States

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Novartis Investigative Site

Eugene, Oregon, 97401, United States

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Novartis Investigative Site

Kingston, Pennsylvania, 95403, United States

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Novartis Investigative Site

Philadelphia, Pennsylvania, 19107, United States

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Novartis Investigative Site

Germantown, Tennessee, 38138, United States

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Novartis Investigative Site

Abilene, Texas, 79606, United States

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Novartis Investigative Site

Austin, Texas, 78705, United States

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Novartis Investigative Site

Austin, Texas, 78731, United States

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Novartis Investigative Site

Austin, Texas, 78793, United States

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Novartis Investigative Site

Fort Worth, Texas, 76102, United States

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Novartis Investigative Site

Fort Worth, Texas, 76104, United States

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Novartis Investigative Site

Harlingen, Texas, 78550, United States

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Novartis Investigative Site

Houston, Texas, 77030, United States

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Novartis Investigative Site

San Antonio, Texas, 78240, United States

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Novartis Investigative Site

Tyler, Texas, 75701, United States

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Novartis Investigative Site

Fairfax, Virginia, 22031, United States

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Novartis Investigative Site

Spokane, Washington, 99204, United States

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Novartis Investigative Site

Arecibo, 00612, Puerto Rico

Location

Related Links

• A Plain Language Trial Summary is available on novctrd.com

MeSH Terms

Conditions

Macular Degeneration; Neurofibromatosis 2

Interventions

brolucizumab; aflibercept

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases; Neuroma, Acoustic; Neurilemmoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neurofibromatoses; Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Neuroma; Neoplastic Syndromes, Hereditary; Vestibulocochlear Nerve Diseases; Retrocochlear Diseases; Ear Diseases; Otorhinolaryngologic Diseases; Otorhinolaryngologic Neoplasms; Cranial Nerve Neoplasms; Cranial Nerve Diseases; Nervous System Diseases; Neurocutaneous Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

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, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: multicenter, randomized, double-masked

Study Record Dates

• First Submitted: October 16, 2018
• First Posted: October 18, 2018
• Study Start: October 30, 2018
• Primary Completion: December 21, 2020
• Study Completion: July 1, 2021
• Last Updated: January 30, 2023
• Results First Posted: July 22, 2022

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share

Locations

US (60); PR (1)