Clinical trial NCT03496012: Efficacy and Safety of BIIB111 for the Treatment of Choroideremia
Official title: A Randomised, Open Label, Outcomes-Assessor Masked, Prospective, Parallel Controlled Group, Phase 3 Clinical Trial of Retinal Gene Therapy for Choroideremia Using an Adeno-Associated Viral Vector (AAV2) Encoding Rab Escort Protein 1 (REP1)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Choroideremia
Keywords: NightstaRx
NSR-REP1
Gene Therapy
AAV
REP1
Timrepigene Emparvovec
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2018-04-12
Enrollment: 169
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of the study is to evaluate the efficacy and safety of a single sub-retinal injection of BIIB111 in participants with choroideremia (CHM).

Detailed description: This study was previously posted by NightstaRx Ltd. In October 2020, sponsorship of the trial was transferred to Biogen.

Eligibility criteria: Key Inclusion Criteria:

* Are willing and able to give informed consent for participation in the study.
* Have a documented genetically-confirmed diagnosis of CHM.
* Have active disease clinically visible within the macular region in the study eye.
* Have a BCVA of 34-73 ETDRS letters (equivalent to worse than or equal to 6/12 or 20/40 Snellen acuity, but better than or equal to 6/60 or 20/200 Snellen acuity) in the study eye.

Key Exclusion Criteria:

* Have a history of amblyopia in the eligible eye.
* Have had previous intraocular surgery performed in the study eye within 3 months of Visit 1.
* Have any other significant ocular or non-ocular disease/disorder which, in the opinion of the investigator, may either put the participants at risk because of participation in the study, or may influence the results of the study, or the participant's ability to participate in the study.
* Have participated in another research study involving an investigational product in the past 12 weeks or received a gene/cell-based therapy at any time previously.
* Are unwilling to use barrier contraception methods, or abstain from sexual intercourse, for a period of 3 months, if treated with AAV2-REP1.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Percentage of Participants With a ≥15 -Letter Improvement From Baseline in Best Corrected Visual Acuity (BCVA) at Month 12 as Measured by the Early Treatment of Diabetic Retinopathy Study (ETDRS) Chart
timeFrame: Month 12
Secondary outcomes:
measure: Change From Baseline in BCVA at Month 12 Reported as Letters Measured by the ETDRS Chart in Study Eye
timeFrame: Baseline, Month 12
measure: Percentage of Participants With a ≥10 -Letter Improvement From Baseline in BCVA at Month 12 Measured by the ETDRS Chart
timeFrame: Month 12
measure: Percentage of Participants With No Decrease From Baseline in BCVA or a Decrease From Baseline in BCVA of <5 ETDRS Letters at Month 12 Measured by the EDRS Chart
timeFrame: Month 12
measure: Change From Baseline in BCVA at Months 4 and 8 Reported as Letters Measured by the ETDRS Chart
timeFrame: Baseline, Months 4 and 8
measure: Change From Baseline in Total Area of Preserved Autofluorescence (AF) at Month 12 in Study Eye
timeFrame: Baseline, Month 12
measure: Change From Baseline in Distance From Foveal Center to Nearest Border of Preserved AF at Month 12 in Study Eye
timeFrame: Baseline, Month 12
measure: Change From Baseline in the Foveal Subfield Thickness Using Spectral Domain Optical Coherence Tomography (SD-OCT) at Month 12 in Study Eye
timeFrame: Baseline, Month 12
measure: Change From Baseline in the Total Macular Volume Using SD-OCT at Month 12 in Study Eye
timeFrame: Baseline, Month 12
measure: Change From Baseline in the Central Horizontal Ellipsoid Width Using SD-OCT at Month 12 in Study Eye
timeFrame: Baseline, Month 12
measure: Change From Baseline in the Central Ellipsoid Area Using SD-OCT at Month 12 in Study Eye
timeFrame: Baseline, Month 12
measure: Change From Baseline in the Choroidal Thickness Using SD-OCT at Month 12 in Study Eye
timeFrame: Baseline, Month 12
measure: Change From Baseline in the Mean Retinal Sensitivity Using Microperimetry at Month 12 in Study Eye
timeFrame: Baseline, Month 12
measure: Change From Baseline in the Bivariate Contour Ellipse Area 63% Using Microperimetry at Month 12 in Study Eye
timeFrame: Baseline, Month 12
measure: Change From Baseline in the Bivariate Contour Ellipse Area 95% Using Microperimetry at Month 12 in Study Eye
timeFrame: Baseline, Month 12
measure: Change From Baseline in Contrast Sensitivity Score at Month 12 in Study Eye
timeFrame: Baseline, Month 12
measure: Change From Baseline in Colour Vision Total Error Score at Month 12 in Study Eye
timeFrame: Baseline, Month 12
measure: Change From Baseline in Reading Speed Test at Month 12 in Study Eye
timeFrame: Baseline, Month 12
measure: Change From Baseline in the 25-Item Visual Function Questionnaire (VFQ-25) Composite Scores at Month 12 in Study Eye
timeFrame: Baseline, Month 12
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Miami
country: United States
facility: Research Site
state: Florida
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: New York
country: United States
facility: Research Site
state: New York
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Madison
country: United States
facility: Research Site
state: Wisconsin
city: Montréal
country: Canada
facility: Research Site
city: Vancouver
country: Canada
facility: Research Site
city: Glostrup
country: Denmark
facility: Research Site
city: Helsinki
country: Finland
facility: Research Site
city: Montpellier
country: France
facility: Research Site
city: Bonn
country: Germany
facility: Research Site
city: Tübingen
country: Germany
facility: Research Site
city: Nijmegen
country: Netherlands
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Oxford
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Davis JL. The Blunt End: Surgical Challenges of Gene Therapy for Inherited Retinal Diseases. Am J Ophthalmol. 2018 Dec;196:xxv-xxix. doi: 10.1016/j.ajo.2018.08.038. Epub 2018 Sep 5.