Study of Safety and Efficacy of Brolucizumab 6 mg Drug Product Intended for Commercialization in Patients With nAMD

Neovascular Age-related Macular Degeneration Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03386474
• Other study ID #: CRTH258A2301E1
• Status: Completed
• Phase: Phase 3
• Start date: January 15, 2018
• Est. completion date: September 6, 2018

Study information

• Verified date: March 2020
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 151
• Est. completion date: September 6, 2018
• Est. primary completion date: September 6, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Macular Degeneration
• Neovascular Age-related Macular Degeneration
• Wet Macular Degeneration

Intervention

Drug:
• Brolucizumab 6 mg
Administered as opthalmic solution for an intravitreal injection to the study eye
• Aflibercept 2 mg
Administered as an opthalmic solution for intravitreal injection to the study eye

Locations

Country	Name	City	State
Puerto Rico	Novartis Investigative Site	Arecibo
Puerto Rico	Novartis Investigative Site	San Juan
United States	Novartis Investigative Site	Abilene	Texas
United States	Novartis Investigative Site	Albuquerque	New Mexico
United States	Novartis Investigative Site	Altamonte Springs	Florida
United States	Novartis Investigative Site	Arcadia	California
United States	Novartis Investigative Site	Austin	Texas
United States	Novartis Investigative Site	Baltimore	Maryland
United States	Novartis Investigative Site	Bloomington	Illinois
United States	Novartis Investigative Site	Boise	Idaho
United States	Novartis Investigative Site	Bridgeport	Connecticut
United States	Novartis Investigative Site	Camp Hill	Pennsylvania
United States	Novartis Investigative Site	Charlotte	North Carolina
United States	Novartis Investigative Site	Cleveland	Ohio
United States	Novartis Investigative Site	Cleveland	Ohio
United States	Novartis Investigative Site	Colorado Springs	Colorado
United States	Novartis Investigative Site	Deerfield Beach	Florida
United States	Novartis Investigative Site	Dublin	Ohio
United States	Novartis Investigative Site	Fairfield	Ohio
United States	Novartis Investigative Site	Fort Myers	Florida
United States	Novartis Investigative Site	Fort Worth	Texas
United States	Novartis Investigative Site	Golden	Colorado
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Huntington Beach	California
United States	Novartis Investigative Site	Indianapolis	Indiana
United States	Novartis Investigative Site	La Jolla	California
United States	Novartis Investigative Site	Las Vegas	Nevada
United States	Novartis Investigative Site	Leawood	Kansas
United States	Novartis Investigative Site	Loma Linda	California
United States	Novartis Investigative Site	Milwaukee	Wisconsin
United States	Novartis Investigative Site	Morgantown	West Virginia
United States	Novartis Investigative Site	Mountain View	California
United States	Novartis Investigative Site	Nashville	Tennessee
United States	Novartis Investigative Site	New London	Connecticut
United States	Novartis Investigative Site	Oakland	California
United States	Novartis Investigative Site	Ocala	Florida
United States	Novartis Investigative Site	Palm Beach Gardens	Florida
United States	Novartis Investigative Site	Pensacola	Florida
United States	Novartis Investigative Site	Peoria	Arizona
United States	Novartis Investigative Site	Phoenix	Arizona
United States	Novartis Investigative Site	Plano	Texas
United States	Novartis Investigative Site	Portland	Maine
United States	Novartis Investigative Site	Redlands	California
United States	Novartis Investigative Site	Reno	Nevada
United States	Novartis Investigative Site	Richmond	Virginia
United States	Novartis Investigative Site	Rochester	New York
United States	Novartis Investigative Site	Rochester	New York
United States	Novartis Investigative Site	Sacramento	California
United States	Novartis Investigative Site	San Antonio	Texas
United States	Novartis Investigative Site	San Antonio	Texas
United States	Novartis Investigative Site	Sarasota	Florida
United States	Novartis Investigative Site	Shawnee Mission	Kansas
United States	Novartis Investigative Site	Shirley	New York
United States	Novartis Investigative Site	Silverdale	Washington
United States	Novartis Investigative Site	Southern Pines	North Carolina
United States	Novartis Investigative Site	Spokane	Washington
United States	Novartis Investigative Site	Syracuse	New York
United States	Novartis Investigative Site	Tallahassee	Florida
United States	Novartis Investigative Site	Toms River	New Jersey
United States	Novartis Investigative Site	University Place	Washington
United States	Novartis Investigative Site	Vero Beach	Florida
United States	Novartis Investigative Site	Waldorf	Maryland
United States	Novartis Investigative Site	Warrenton	Virginia
United States	Novartis Investigative Site	Winter Haven	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Ocular and Non-Ocular Treatment Emergent Adverse Events	Number of participants with ocular and non-ocular treatment emergent events with the new formulation brolucizumab 6 mg in this extension trial up to week 24 vs. the corresponding last 6 months of brolucizumab treatment in the Core trial >= 2%. Safety assessment of the new formulation brolucizumab 6 mg was based on a within-patient comparison with the last 6 months of corresponding Core safety data. Missing brolucizumab data were imputed using last observation carried forward (LOCF).	Up to Week 24
Secondary	Change of Loss in BCVA of 15 Letters or More From Extension Baseline at Each Post-baseline Visit	Best-corrected visual acuity for the study eye was tested at all study visits in a sitting position using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing protocol at an initial testing distance of 4 meters. Outcome measure was prespecified for brolucizumab arm only. Neither 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 presented descriptively for only brolucizumab in line with study objective. No formal hypothesis testing was planned. Missing brolucizumab data were imputed using last observation carried forward (LOCF).	Extension Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24
Secondary	Change in BCVA From Extension Baseline at Each Post-baseline Visit	Best-corrected visual acuity for the study eye was tested at all study visits in a sitting position using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing protocol at an initial testing distance of 4 meters. Outcome measure was prespecified for brolucizumab arm only. 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. Missing brolucizumab data were imputed using last observation carried forward (LOCF).	Extension baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24
Secondary	Patients With Positive q12w Treatment Status at Week 20	The estimate for the proportion of patients with a positive q12w treatment status at Week 24 was derived from Kaplan Meier time-to-event analyses for the event 'first q8w-need'. The outcome of the Kaplan-Meier analysis was estimated probability for maintaining on q12w up to the Disease Activity Assessment (DAA) at exWeek 20. Outcome measure was prespecified for brolucizumab arm only. 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. Missing brolucizumab data were imputed using last observation carried forward (LOCF).	Week 20
Secondary	Change in Central Sub-Field Thickness (CSFT) From Extension Baseline at Each Post-baseline Visit	Measurement of the central subfield thickness of the retina was assessed using Optical Coherence Tomography (OCT) at each visit for the study eye. Outcome measure was prespecified for brolucizumab arm only. 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. Missing brolucizumab data were imputed using last observation carried forward (LOCF).	Extension Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24
Secondary	Percentage of Subjects With Positive Anti-drug Antibody (ADA) Status for Brolucuzumab 6 mg in Extension	Positive integrated anti-drug antibodies (ADA) status is defined as induced ADA status with ADA negative at pre-dose and a post-dose titer value of greater than or equal to 30 at any time point or boosted ADA status with ADA positive at pre-dose and a post-dose titer value increase by more than 3-fold (1 dilution) at any time point. Outcome measure was prespecified for brolucizumab arm only. 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. Missing brolucizumab data were imputed using last observation carried forward (LOCF).	Extension Baseline, Week 8, Week 16, Week 24

External Links

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