Efficacy and Safety of BIIB111 for the Treatment of Choroideremia (STAR)
Primary Purpose
Choroideremia
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
BIIB111
Sponsored by
About this trial
This is an interventional treatment trial for Choroideremia focused on measuring NightstaRx, NSR-REP1, Gene Therapy, AAV, REP1, Timrepigene Emparvovec
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.
Sites / Locations
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
No Intervention
Arm Label
BIIB111 High Dose
BIIB111 Low Dose
Untreated Control Group
Arm Description
Participants will receive a single administration of high dose BIIB111 in one eye through sub-retinal injection after vitrectomy.
Participants will receive a single administration of low dose BIIB111 in one eye through sub-retinal injection after vitrectomy.
Participants will receive no sham surgery or study medication.
Outcomes
Primary Outcome Measures
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
BCVA will be assessed for both eyes using the Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart. BCVA test should be performed prior to pupil dilation, and distance refraction should be carried out before BCVA is measured. Initially, letters are read at a distance of 4 meters from the chart. If <20 letters are read at 4 meters, testing at 1 meter should be performed. BCVA is to be reported as number of letters read correctly by the participant using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved.
Secondary Outcome Measures
Change from Baseline in BCVA at Month 12 Measured by the ETDRS Chart
BCVA will be assessed for both eyes using the Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart. BCVA test should be performed prior to pupil dilation, and distance refraction should be carried out before BCVA is measured. Initially, letters are read at a distance of 4 meters from the chart. If <20 letters are read at 4 meters, testing at 1 meter should be performed. BCVA is to be reported as number of letters read correctly by the participant using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved.
Percentage of Participants with a ≥10-Letter Improvement from Baseline in BCVA at Month 12 Measured by the ETDRS Chart
BCVA will be assessed for both eyes using the Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart. BCVA test should be performed prior to pupil dilation, and distance refraction should be carried out before BCVA is measured. Initially, letters are read at a distance of 4 meters from the chart. If <20 letters are read at 4 meters, testing at 1 meter should be performed. BCVA is to be reported as number of letters read correctly by the participant using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved.
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
BCVA will be assessed for both eyes using the Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart. BCVA test should be performed prior to pupil dilation, and distance refraction should be carried out before BCVA is measured. Initially, letters are read at a distance of 4 meters from the chart. If <20 letters are read at 4 meters, testing at 1 meter should be performed. BCVA is to be reported as number of letters read correctly by the participant using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved.
Change from Baseline in BCVA at Months 4 and 8
BCVA will be assessed for both eyes using the Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart. BCVA test should be performed prior to pupil dilation, and distance refraction should be carried out before BCVA is measured. Initially, letters are read at a distance of 4 meters from the chart. If <20 letters are read at 4 meters, testing at 1 meter should be performed. BCVA is to be reported as number of letters read correctly by the participant using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved.
Change from Baseline in Total Area of Preserved Autofluorescence (AF) at Month 12
Change from Baseline in the Area of Preserved Ellipsoid Zone Using Spectral Domain Optical Coherence Tomography (SD-OCT) at Month 12
Change from Baseline in Microperimetry at Month 12
Change from Baseline in Contrast Sensitivity Score at Month 12
Change from baseline in contrast sensitivity in the study eye is measured using a Pelli Robson contrast sensitivity chart at 1 meter. The contrast sensitivity chart contains letters that are darkest at the top and then get progressively lighter. Scores range from 0 to 48 and are based on the number of letters read correctly. A negative change from baseline indicates a worsening in contrast sensitivity and a positive change from baseline indicates an improvement.
Change from Baseline in Colour Vision at Month 12
Change from Baseline in Reading Speed Test at Month 12
Change from Baseline in the 25-Item Visual Function Questionnaire (VFQ-25) at Month 12
VFQ-25 questionnaire measures dimensions of self-reported vision-targeted health status that are most important to persons with eye disease. Total score ranges from 0-100, where a score of 0 represents the worst outcome and 100 represents the best outcome.
Full Information
NCT ID
NCT03496012
First Posted
March 7, 2018
Last Updated
February 9, 2023
Sponsor
NightstaRx Ltd, a Biogen Company
1. Study Identification
Unique Protocol Identification Number
NCT03496012
Brief Title
Efficacy and Safety of BIIB111 for the Treatment of Choroideremia
Acronym
STAR
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
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Completed
Study Start Date
December 11, 2017 (Actual)
Primary Completion Date
December 1, 2020 (Actual)
Study Completion Date
December 1, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NightstaRx Ltd, a Biogen Company
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Choroideremia
Keywords
NightstaRx, NSR-REP1, Gene Therapy, AAV, REP1, Timrepigene Emparvovec
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
170 (Actual)
8. Arms, Groups, and Interventions
Arm Title
BIIB111 High Dose
Arm Type
Experimental
Arm Description
Participants will receive a single administration of high dose BIIB111 in one eye through sub-retinal injection after vitrectomy.
Arm Title
BIIB111 Low Dose
Arm Type
Experimental
Arm Description
Participants will receive a single administration of low dose BIIB111 in one eye through sub-retinal injection after vitrectomy.
Arm Title
Untreated Control Group
Arm Type
No Intervention
Arm Description
Participants will receive no sham surgery or study medication.
Intervention Type
Genetic
Intervention Name(s)
BIIB111
Other Intervention Name(s)
AAV2-REP1
Intervention Description
Administered as specified in the treatment arm.
Primary Outcome Measure Information:
Title
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
Description
BCVA will be assessed for both eyes using the Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart. BCVA test should be performed prior to pupil dilation, and distance refraction should be carried out before BCVA is measured. Initially, letters are read at a distance of 4 meters from the chart. If <20 letters are read at 4 meters, testing at 1 meter should be performed. BCVA is to be reported as number of letters read correctly by the participant using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved.
Time Frame
Month 12
Secondary Outcome Measure Information:
Title
Change from Baseline in BCVA at Month 12 Measured by the ETDRS Chart
Description
BCVA will be assessed for both eyes using the Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart. BCVA test should be performed prior to pupil dilation, and distance refraction should be carried out before BCVA is measured. Initially, letters are read at a distance of 4 meters from the chart. If <20 letters are read at 4 meters, testing at 1 meter should be performed. BCVA is to be reported as number of letters read correctly by the participant using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved.
Time Frame
Month 12
Title
Percentage of Participants with a ≥10-Letter Improvement from Baseline in BCVA at Month 12 Measured by the ETDRS Chart
Description
BCVA will be assessed for both eyes using the Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart. BCVA test should be performed prior to pupil dilation, and distance refraction should be carried out before BCVA is measured. Initially, letters are read at a distance of 4 meters from the chart. If <20 letters are read at 4 meters, testing at 1 meter should be performed. BCVA is to be reported as number of letters read correctly by the participant using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved.
Time Frame
Month 12
Title
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
Description
BCVA will be assessed for both eyes using the Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart. BCVA test should be performed prior to pupil dilation, and distance refraction should be carried out before BCVA is measured. Initially, letters are read at a distance of 4 meters from the chart. If <20 letters are read at 4 meters, testing at 1 meter should be performed. BCVA is to be reported as number of letters read correctly by the participant using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved.
Time Frame
Month 12
Title
Change from Baseline in BCVA at Months 4 and 8
Description
BCVA will be assessed for both eyes using the Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity (VA) chart. BCVA test should be performed prior to pupil dilation, and distance refraction should be carried out before BCVA is measured. Initially, letters are read at a distance of 4 meters from the chart. If <20 letters are read at 4 meters, testing at 1 meter should be performed. BCVA is to be reported as number of letters read correctly by the participant using the ETDRS Scale (ranging from 0 to 100 letters) in the study eye. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved.
Time Frame
Months 4 and 8
Title
Change from Baseline in Total Area of Preserved Autofluorescence (AF) at Month 12
Time Frame
Month 12
Title
Change from Baseline in the Area of Preserved Ellipsoid Zone Using Spectral Domain Optical Coherence Tomography (SD-OCT) at Month 12
Time Frame
Months 12
Title
Change from Baseline in Microperimetry at Month 12
Time Frame
Month 12
Title
Change from Baseline in Contrast Sensitivity Score at Month 12
Description
Change from baseline in contrast sensitivity in the study eye is measured using a Pelli Robson contrast sensitivity chart at 1 meter. The contrast sensitivity chart contains letters that are darkest at the top and then get progressively lighter. Scores range from 0 to 48 and are based on the number of letters read correctly. A negative change from baseline indicates a worsening in contrast sensitivity and a positive change from baseline indicates an improvement.
Time Frame
Month 12
Title
Change from Baseline in Colour Vision at Month 12
Time Frame
Month 12
Title
Change from Baseline in Reading Speed Test at Month 12
Time Frame
Month 12
Title
Change from Baseline in the 25-Item Visual Function Questionnaire (VFQ-25) at Month 12
Description
VFQ-25 questionnaire measures dimensions of self-reported vision-targeted health status that are most important to persons with eye disease. Total score ranges from 0-100, where a score of 0 represents the worst outcome and 100 represents the best outcome.
Time Frame
Month 12
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Biogen
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Research Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Research Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Research Site
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Research Site
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45242
Country
United States
Facility Name
Research Site
City
Portland
State/Province
Oregon
ZIP/Postal Code
97232
Country
United States
Facility Name
Research Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
Research Site
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53705
Country
United States
Facility Name
Research Site
City
Montréal
ZIP/Postal Code
H3A 0E7
Country
Canada
Facility Name
Research Site
City
Vancouver
ZIP/Postal Code
V5Z 3N9
Country
Canada
Facility Name
Research Site
City
Glostrup
Country
Denmark
Facility Name
Research Site
City
Helsinki
ZIP/Postal Code
00290
Country
Finland
Facility Name
Research Site
City
Montpellier
Country
France
Facility Name
Research Site
City
Bonn
ZIP/Postal Code
53127
Country
Germany
Facility Name
Research Site
City
Tübingen
Country
Germany
Facility Name
Research Site
City
Nijmegen
Country
Netherlands
Facility Name
Research Site
City
Manchester
ZIP/Postal Code
M13 9WL
Country
United Kingdom
Facility Name
Research Site
City
Oxford
ZIP/Postal Code
OX3 9DU
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
30194931
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.
Results Reference
derived
Learn more about this trial
Efficacy and Safety of BIIB111 for the Treatment of Choroideremia
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