Clinical trial NCT03710564: 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
Official title: A Multicenter, Randomized, Double-masked Phase 3a Study to Assess Safety and Efficacy of Brolucizumab 6 mg q4 Weeks Compared to Aflibercept 2 mg q4 Weeks in Patients With Neovascular Age-related Macular Degeneration (nAMD) With Persistent Retinal Fluid (MERLIN)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Age-Related Macular Degeneration
Keywords: neovascular age-related macular degeneration
nAMD
intravitreal injection
IVT
anti-VEGF
brolucizumab
aflibercept
EYLEA
double-masked
MERLIN
BEOVU
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2018-10-18
Enrollment: 535
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: multicenter, randomized, double-masked
Primary purpose: TREATMENT

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.

Detailed description: This was a Phase III, multi-center, randomized, double-masked, parallel group study with 2 masked arms in which participants were randomized 2:1 to receive brolucizumab or aflibercept. All participants had study visits every 4 weeks through week 104.

The study consisted of three study periods:

Screening Period: The screening period lasted up to 2 weeks prior to administration of the first dose of study treatment, dependent upon confirmation of the patient meeting eligibility criteria.

Double-Masked Treatment Period: Participants meeting eligibility criteria entered the treatment period and were randomized in a 2:1 ratio into one of the following 2 masked treatment arms at the Baseline visit: Brolucizumab 6 mg injected every 4 weeks or Aflibercept 2 mg injected every 4 weeks. Treatment period lasted up to week 100.

Safety Follow up Period: Participants were followed up for safety during 4 weeks after the last dose of study treatment. Including the Screening Period, the total study duration for a participant was up to 106 weeks.

Some participants were eligible to continue into an extension study in order to receive treatment with brolucizumab (a) after completing the 104 -week double-masked treatment period, (b) upon meeting all inclusion/exclusion criteria for the extension study, and (c) based on Investigator's judgment that the participant was expected to benefit from treatment with brolucizumab.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Change From Baseline in Best-Corrected Visual Acuity (BCVA) at Week 52
timeFrame: Baseline, week 52
Secondary outcomes:
measure: Stable Visual Acuity (VA) or Improvement in VA at Week 52 and Week 104
timeFrame: Baseline, weeks 52 and 104
measure: Loss in Best-Corrected Visual Acuity (BCVA) of 5 Letters or More
timeFrame: 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
measure: Loss in Best-Corrected Visual Acuity (BCVA) of 10 Letters or More
timeFrame: 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
measure: Loss in Best-Corrected Visual Acuity (BCVA) of 15 Letters or More
timeFrame: 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
measure: Gain in Best-Corrected Visual Acuity (BCVA) of 5 Letters or More
timeFrame: 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
measure: Gain in Best-Corrected Visual Acuity (BCVA) of 10 Letters or More
timeFrame: 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
measure: Gain in Best-Corrected Visual Acuity (BCVA) of 15 Letters or More
timeFrame: 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
measure: Change in Central Subfield Thickness (CST) From Baseline
timeFrame: 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
measure: Number of Participants With Intraretinal Fluid (IRF)
timeFrame: 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
measure: Number of Participants With Subretinal Fluid (SRF)
timeFrame: 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
measure: Number of Participants With Sub-Retinal Pigment Epithelium (Sub-RPE) Fluid
timeFrame: 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
measure: Number of Participants With Fluid-free Status (no IRF, SRF or Sub-RPE Fluid)
timeFrame: 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
measure: Time to First Dry Retina (no IRF or SRF)
timeFrame: Baseline, Up to Week 104 (assessments every 4 weeks)
measure: Time to Sustained Dry Retina (no IRF or SRF at ≥ 2 Consecutive Visits)
timeFrame: Baseline, Up to Week 104 (assessments every 4 weeks)
measure: Number of Participants With Anti-drug Antibody (ADA) Negative Status
timeFrame: Baseline, weeks 4, 12, 24, 36, 52, 76 and 104
measure: Free Brolucizumab Serum Concentration
timeFrame: pre-dose a baseline, weeks 4, 12, 24, 36, 52, 76 and 104
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Novartis Investigative Site
state: Arizona
city: Phoenix
country: United States
facility: Novartis Investigative Site
state: Arizona
city: Phoenix
country: United States
facility: Novartis Investigative Site
state: Arizona
city: Beverly Hills
country: United States
facility: Novartis Investigative Site
state: California
city: Huntington Beach
country: United States
facility: Novartis Investigative Site
state: California
city: Mountain View
country: United States
facility: Novartis Investigative Site
state: California
city: Oakland
country: United States
facility: Novartis Investigative Site
state: California
city: Oxnard
country: United States
facility: Novartis Investigative Site
state: California
city: Palo Alto
country: United States
facility: Novartis Investigative Site
state: California
city: Redlands
country: United States
facility: Novartis Investigative Site
state: California
city: Sacramento
country: United States
facility: Novartis Investigative Site
state: California
city: San Francisco
country: United States
facility: Novartis Investigative Site
state: California
city: Santa Barbara
country: United States
facility: Novartis Investigative Site
state: California
city: Colorado Springs
country: United States
facility: Novartis Investigative Site
state: Colorado
city: Golden
country: United States
facility: Novartis Investigative Site
state: Colorado
city: Deerfield Beach
country: United States
facility: Novartis Investigative Site
state: Florida
city: Fort Lauderdale
country: United States
facility: Novartis Investigative Site
state: Florida
city: Fort Myers
country: United States
facility: Novartis Investigative Site
state: Florida
city: Miami
country: United States
facility: Novartis Investigative Site
state: Florida
city: Mount Dora
country: United States
facility: Novartis Investigative Site
state: Florida
city: Pensacola
country: United States
facility: Novartis Investigative Site
state: Florida
city: Saint Petersburg
country: United States
facility: Novartis Investigative Site
state: Florida
city: Stuart
country: United States
facility: Novartis Investigative Site
state: Florida
city: Marietta
country: United States
facility: Novartis Investigative Site
state: Georgia
city: 'Aiea
country: United States
facility: Novartis Investigative Site
state: Hawaii
city: Wheaton
country: United States
facility: Novartis Investigative Site
state: Illinois
city: West Des Moines
country: United States
facility: Novartis Investigative Site
state: Iowa
city: Lenexa
country: United States
facility: Novartis Investigative Site
state: Kansas
city: New Orleans
country: United States
facility: Novartis Investigative Site
state: Louisiana
city: West Monroe
country: United States
facility: Novartis Investigative Site
state: Louisiana
city: Waldorf
country: United States
facility: Novartis Investigative Site
state: Maryland
city: Boston
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Boston
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Springfield
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Royal Oak
country: United States
facility: Novartis Investigative Site
state: Michigan
city: Saint Louis
country: United States
facility: Novartis Investigative Site
state: Missouri
city: Las Vegas
country: United States
facility: Novartis Investigative Site
state: Nevada
city: Reno
country: United States
facility: Novartis Investigative Site
state: Nevada
city: Bloomfield
country: United States
facility: Novartis Investigative Site
state: New Jersey
city: Toms River
country: United States
facility: Novartis Investigative Site
state: New Jersey
city: Syracuse
country: United States
facility: Novartis Investigative Site
state: New York
city: Charlotte
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Cleveland
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Fairfield
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Eugene
country: United States
facility: Novartis Investigative Site
state: Oregon
city: Kingston
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Germantown
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Abilene
country: United States
facility: Novartis Investigative Site
state: Texas
city: Austin
country: United States
facility: Novartis Investigative Site
state: Texas
city: Austin
country: United States
facility: Novartis Investigative Site
state: Texas
city: Austin
country: United States
facility: Novartis Investigative Site
state: Texas
city: Fort Worth
country: United States
facility: Novartis Investigative Site
state: Texas
city: Fort Worth
country: United States
facility: Novartis Investigative Site
state: Texas
city: Harlingen
country: United States
facility: Novartis Investigative Site
state: Texas
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: San Antonio
country: United States
facility: Novartis Investigative Site
state: Texas
city: Tyler
country: United States
facility: Novartis Investigative Site
state: Texas
city: Fairfax
country: United States
facility: Novartis Investigative Site
state: Virginia
city: Spokane
country: United States
facility: Novartis Investigative Site
state: Washington
city: Arecibo
country: Puerto Rico
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: