Clinical trial NCT03386474: Study of Safety and Efficacy of Brolucizumab 6 mg Drug Product Intended for Commercialization in Patients With nAMD
Official title: A 24-week, Double-masked, Multicenter, Two-arm Extension Study to Collect Safety and Efficacy Data on Brolucizumab 6 mg Drug Product Intended for Commercialization in Patients With Neovascular Age-related Macular Degeneration Who Have Completed the CRTH258A2301 Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Neovascular Age-related Macular Degeneration
Keywords: double-masked, extension study
neovascular age-related macular degeneration
intravitreal injection
brolucizumab
aflibercept
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2017-12-29
Enrollment: 151
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this extension study was to assess the safety and efficacy of the new formulation of brolucizumab 6 mg ophthalmic solution when given to the same patients who received brolucizumab in the core trial CRTH258A2301 (also known as CRTH258-C002). The medical condition treated in the core and extension trials was neo-vascular age-related macular degeneration (nAMD).

Detailed description: Subjects in the United States who had completed the 96 week core trial, CRTH258A2301 (also referred as CRTH258-C002), were eligible to participate in the extension trial provided the core trial Visit 26 at week 96, was less than or equal to 12 weeks from the Baseline Visit in the extension trial, CRTH258A2301E1.

Subjects who were treated with aflibercept during the core trial and met the eligibility requirements of this extension trial continued to receive aflibercept in this extension trial in order to maintain the masking during the extension trial. No hypothesis testing or descriptive analyses were planned.

Subjects who were treated in the core trial with brolucizumab 3mg or brolucizumab 6 mg, and met the eligibility requirements of this extension trial, received the new formulation of brolucizumab 6 mg solution in the extension trial.

Enrolled subjects were to receive three intravitreal (IVT) ophthalmic injections. The study eye was the same eye that received the treatment in the core study. The extension trial consisted of 7 study visits at 4 week intervals over a period of 24 weeks.

Assessment of the efficacy and safety of brolucizumab 6 mg was based on a within-patient comparison with the last 6 months of corresponding core-study efficacy and safety data serving as the reference. Neither the patient selection process nor expected sample sizes supported a valid comparison between aflibercept and brolucizumab. The aflibercept arm was included only to maintain the masking in the extension trial. Data was presented descriptively for only brolucizumab in line with the study objective. No formal hypothesis testing was planned.

Eligibility criteria: Inclusion Criteria:

* Sign written informed consent
* Completed the core study, CRTH258A2301, also known as CRTH258-C002 as defined by assessments at Visit 26/Week 96 within ≤12 weeks of the baseline.

Exclusion Criteria:

* Patient discontinued the treatment or the core study prematurely at any time
* Patient received standard of care treatment for nAMD after completion of the core study
* Pregnant or nursing women and women of child-bearing potential
* Stroke or MI (myocardial infarction) within 3 months of the baseline extension visit

Primary outcomes:
measure: Number of Participants With Ocular and Non-Ocular Treatment Emergent Adverse Events
timeFrame: Up to Week 24
Secondary outcomes:
measure: Change of Loss in BCVA of 15 Letters or More From Extension Baseline at Each Post-baseline Visit
timeFrame: Extension Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24
measure: Change in BCVA From Extension Baseline at Each Post-baseline Visit
timeFrame: Extension baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24
measure: Patients With Positive q12w Treatment Status at Week 20
timeFrame: Week 20
measure: Change in Central Sub-Field Thickness (CSFT) From Extension Baseline at Each Post-baseline Visit
timeFrame: Extension Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24
measure: Percentage of Subjects With Positive Anti-drug Antibody (ADA) Status for Brolucuzumab 6 mg in Extension
timeFrame: Extension Baseline, Week 8, Week 16, Week 24
Other outcomes:
Locations:
city: Peoria
country: United States
facility: Novartis Investigative Site
state: Arizona
city: Phoenix
country: United States
facility: Novartis Investigative Site
state: Arizona
city: Arcadia
country: United States
facility: Novartis Investigative Site
state: California
city: Huntington Beach
country: United States
facility: Novartis Investigative Site
state: California
city: La Jolla
country: United States
facility: Novartis Investigative Site
state: California
city: Loma Linda
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: Redlands
country: United States
facility: Novartis Investigative Site
state: California
city: Sacramento
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: Bridgeport
country: United States
facility: Novartis Investigative Site
state: Connecticut
city: New London
country: United States
facility: Novartis Investigative Site
state: Connecticut
city: Altamonte Springs
country: United States
facility: Novartis Investigative Site
state: Florida
city: Deerfield Beach
country: United States
facility: Novartis Investigative Site
state: Florida
city: Fort Myers
country: United States
facility: Novartis Investigative Site
state: Florida
city: Ocala
country: United States
facility: Novartis Investigative Site
state: Florida
city: Palm Beach Gardens
country: United States
facility: Novartis Investigative Site
state: Florida
city: Pensacola
country: United States
facility: Novartis Investigative Site
state: Florida
city: Sarasota
country: United States
facility: Novartis Investigative Site
state: Florida
city: Tallahassee
country: United States
facility: Novartis Investigative Site
state: Florida
city: Vero Beach
country: United States
facility: Novartis Investigative Site
state: Florida
city: Winter Haven
country: United States
facility: Novartis Investigative Site
state: Florida
city: Boise
country: United States
facility: Novartis Investigative Site
state: Idaho
city: Bloomington
country: United States
facility: Novartis Investigative Site
state: Illinois
city: Indianapolis
country: United States
facility: Novartis Investigative Site
state: Indiana
city: Leawood
country: United States
facility: Novartis Investigative Site
state: Kansas
city: Shawnee Mission
country: United States
facility: Novartis Investigative Site
state: Kansas
city: Portland
country: United States
facility: Novartis Investigative Site
state: Maine
city: Baltimore
country: United States
facility: Novartis Investigative Site
state: Maryland
city: Waldorf
country: United States
facility: Novartis Investigative Site
state: Maryland
city: Las Vegas
country: United States
facility: Novartis Investigative Site
state: Nevada
city: Reno
country: United States
facility: Novartis Investigative Site
state: Nevada
city: Toms River
country: United States
facility: Novartis Investigative Site
state: New Jersey
city: Albuquerque
country: United States
facility: Novartis Investigative Site
state: New Mexico
city: Rochester
country: United States
facility: Novartis Investigative Site
state: New York
city: Rochester
country: United States
facility: Novartis Investigative Site
state: New York
city: Shirley
country: United States
facility: Novartis Investigative Site
state: New York
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: Southern Pines
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Cleveland
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Cleveland
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Dublin
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Fairfield
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Camp Hill
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Nashville
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: Fort Worth
country: United States
facility: Novartis Investigative Site
state: Texas
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: Plano
country: United States
facility: Novartis Investigative Site
state: Texas
city: San Antonio
country: United States
facility: Novartis Investigative Site
state: Texas
city: San Antonio
country: United States
facility: Novartis Investigative Site
state: Texas
city: Richmond
country: United States
facility: Novartis Investigative Site
state: Virginia
city: Warrenton
country: United States
facility: Novartis Investigative Site
state: Virginia
city: Silverdale
country: United States
facility: Novartis Investigative Site
state: Washington
city: Spokane
country: United States
facility: Novartis Investigative Site
state: Washington
city: University Place
country: United States
facility: Novartis Investigative Site
state: Washington
city: Morgantown
country: United States
facility: Novartis Investigative Site
state: West Virginia
city: Milwaukee
country: United States
facility: Novartis Investigative Site
state: Wisconsin
city: Arecibo
country: Puerto Rico
facility: Novartis Investigative Site
city: San Juan
country: Puerto Rico
facility: Novartis Investigative Site
Study officials:
References: