Long-term Safety and Efficacy Follow-up of BIIB111 for the Treatment of Choroideremia and BIIB112 for the Treatment of X-Linked Retinitis Pigmentosa

Study Overview
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Brief Summary
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The objective of the study is to evaluate the long-term safety and efficacy of a sub-retinal injection of BIIB111 in participants with Choroideremia (CHM) who have been previously treated with BIIB111 and who have exited an antecedent study; these treated participants will be compared with untreated control participants who have exited the STAR (NCT03496012) study and BIIB112 in participants with X-linked retinitis pigmentosa (XLRP) who have been previously treated with BIIB112 and who have exited an antecedent study.

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

Official Title
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A Long-term Follow-up Study to Evaluate the Safety and Efficacy of Retinal Gene Therapy in Subjects With Choroideremia Previously Treated With Adeno-Associated Viral Vector Encoding Rab Escort Protein-1 (AAV2-REP1) and in Subjects With X-Linked Retinitis Pigmentosa Previously Treated With Adeno-Associated Viral Vector Encoding RPGR (AAV8-RPGR) in an Antecedent Study

Conditions
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Choroideremia, X-Linked Retinitis Pigmentosa

Intervention / Treatment
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* Genetic: BIIB111
* Genetic: BIIB112


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: CHM Participants a. Have participated in and exited from an interventional study that investigated the safety and efficacy of a sub-retinal injection of BIIB111 for CHM. XLRP Participants a. Have received a sub-retinal injection of BIIB112 for XLRP and have exited an antecedent study. Key Exclusion Criteria: Participants are not eligible for study participation if they meet the following exclusion criterion. a. In the opinion of the Investigator and/or the Sponsor, it is not in the participant's best interest to participate in the study. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIIB111<br>Participants previously treated with sub-retinal injection of BIIB111 in antecedent studies 273CH301 (NCT03496012) and 273CH203 (NCT03507686) will be enrolled. Participants previously treated with this same sub-retinal injection (rAAV2-REP1) in antecedent studies 20150371 (NCT02553135), Pro00028599 (NCT02077361), THOR-TUE-01 (NCT02671539), CHM09/01 (NCT01461213) and REGEN2015 (NCT02407678) will also be invited for enrollment. This is a follow-up study, investigational product was administered in the previous study. | Genetic: BIIB111<br>* Administered as specified in the treatment arm.<br>* Other names: rAAV2-REP1;|
| Experimental: BIIB112<br>Participants previously treated with sub-retinal injection of BIIB112 in the antecedent study 274RP101 (NCT03116113) will be enrolled. This is a follow-up study, investigational product was administered in the previous study. | Genetic: BIIB112<br>* Administered as specified in the treatment arm.<br>* Other names: AAV8-RPGR;|
| No Intervention: Untreated<br>Untreated participants who served as controls in the antecedent study 273CH301 (NCT03496012), investigating treatment with BIIB111, will be enrolled. This is a follow-up study, participants will not be administered study medication nor receive a sham surgery. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Adverse Events (AEs) |  | Up to 5 years | 
| Ophthalmic Examination Assessment: Intraocular Pressure (IOP) |  | Up to 5 years | 
| Ophthalmic Examination Assessment: Abnormal Slit Lamp Examination |  | Up to 5 years | 
| Ophthalmic Examination Assessment: Lens Opacity Grading |  | Up to 5 years | 
| Ophthalmic Examination Assessment: Anterior Chamber and Vitreous Inflammation |  | Up to 5 years | 
| Ophthalmic Examination Assessment: Indirect Ophthalmoscopy |  | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Best-Corrected Visual Acuity (BCVA) | 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. | Up to 5 years | 
| Percentage of Participants with no Decrease from Baseline in BCVA or a Decrease from Baseline in BCVA of <5 ETDRS Letters in Choroideremia (CHM) Participants | 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. | Up to 5 years | 
| Percentage of Participants with an Increase from Baseline in BCVA of ≥10 ETDRS Letters in CHM Participants | 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. | Up to 5 years | 
| Percentage of Participants with an Increase from Baseline in BCVA of ≥15 ETDRS Letters in CHM Participants | 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. | Up to 5 years | 
| Assessment of Fundus Autofluorescence (AF) at Each Visit | Fundus Autofluoroscence will be performed on both eyes to assess the change in the area of viable retinal tissue. It will be reported in square millimetres (mm^2). | Up to 5 years | 
| Assessment of Fundus Photography at Each Visit | Fundus photography will be performed on both eyes following the dilation of the participant's pupils. | Up to 5 years | 
| Assessment of Spectral Domain Optical Coherence Tomography (SD-OCT) at Each Visit | SD-OCT will be performed on both eyes to assess the foveal changes and other potential anatomic changes. The measurements were taken after dilation of the participant's pupil and would be reported in micrometres (µm). | Up to 5 years | 
| Assessment of Microperimetry at Each Visit | Microperimetry will be performed on both eyes to assess changes in retinal sensitivity within the macula. It will be reported in decibels (dB). | Up to 5 years | 
| Change from Baseline in 25-Item Visual Function Questionnaire (VFQ-25) | 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. | Up to 5 years | 
| Change from Baseline in Visual Field | The outcome measure will be assessed in BIIB112-treated participants. | Up to 5 years | 
| Percentage of Participants with an Increase from Baseline in Luminance Visual Acuity (LLVA) of ≥10 ETDRS Letters in BIIB112-treated Participants | The LLVA was measured by placing a 2.0-log-unit neutral density filter over the best correction for that eye and having the participant read the normally illuminated ETDRS chart. The assessment was performed prior to dilating the eyes. Initially, letters are read at a distance of 4 metres from the chart. If <20 letters are read at 4 metres, testing at 1 metre should be performed. BCVA is to be reported as number of letters read correctly by the participant. | 18 Months to 60 Months, Post-Day 0 Visits | 
| Percentage of Participants with an Increase from Baseline in Luminance Visual Acuity (LLVA) of ≥15 ETDRS Letters in BIIB112-treated Participants | The LLVA was measured by placing a 2.0-log-unit neutral density filter over the best correction for that eye and having the participant read the normally illuminated ETDRS chart. The assessment was performed prior to dilating the eyes. Initially, letters are read at a distance of 4 metres from the chart. If <20 letters are read at 4 metres, testing at 1 metre should be performed. BCVA is to be reported as number of letters read correctly by the participant. | 18 Months to 60 Months, Post-Day 0 Visits | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NightstaRx, Biogen, NSR-REP1, CHM, Gene Therapy, AAV, REP1, AAV8, RPGR