Gene Therapy Trial for the Treatment of X-linked Retinitis Pigmentosa Associated With Variants in the RPGR Gene

Study Overview
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Brief Summary
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A clinical trial of AAV5-RPGR vector for patients with X-linked retinitis pigmentosa (XLRP)

Detailed Description
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Deferred Treatment

Official Title
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Phase 3 Randomized, Controlled Study of AAV5-RPGR for the Treatment of X-linked Retinitis Pigmentosa Associated With Variants in the RPGR Gene

Conditions
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X-Linked Retinitis Pigmentosa

Intervention / Treatment
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* Biological: Genetic: AAV5-RPGR
* Biological: Genetic: AAV5-RPGR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female 3 years of age or older has XLRP confirmed by a retinal specialist and has a predicted disease-causing sequence variant in RPGR confirmed by an accredited laboratory. Exclusion Criteria: -

Ages Eligible for Study
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Minimum Age: 3 Years

Sexes Eligible for Study
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All

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Bilateral, subretinal administration of AAV5-RPGR - immediate treatment group
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental - Immediate Treatment<br>RPGR4e11 | Biological: Genetic: AAV5-RPGR<br>* Bilateral, sub-retinal administration of AAV5-RPGR - immediate treatment group<br>|
| Other: Deferred Treatment<br>Deferred Treatment | Biological: Genetic: AAV5-RPGR<br>* No intervention - deferred treatment group (Bilateral, sub-retinal administration of AAV5-RPGR to be administered in the follow-up study)<br>|
| Active Comparator: Experimental Immediate Treatment<br>RPGR2e11 | Biological: Genetic: AAV5-RPGR<br>* Bilateral, sub-retinal administration of AAV5-RPGR - immediate treatment group<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to Week 52 in vision-guided mobility assessment (VMA) as measured by the ability of the participant to navigate through a VMA maze | Change from baseline to Week 52 in vision-guided mobility assessment (VMA) as measured by the ability of the participant to navigate through a VMA maze | 52 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in retinal function as assessed by mean retinal sensitivity within the central 10 degrees (MRS10) in static perimetry at Week 52 | Mean retinal sensitivity within the central 10 degrees (MRS10) in static perimetry at Week 52 | Day 1 - Week 52 | 
| Change in retinal function as assessed by pointwise responder in full visual field at Week 52 | Pointwise responder in full visual field at Week 52 | Day 1 - Week 52 | 
| Change in retinal function as assessed by pointwise responder in the central 30 degrees visual field at Week 52 | Pointwise responder in the central 30 degrees visual field at Week 52 | Day 1 - Week 52 | 
| Change in retinal function as assessed by mean retinal sensitivity within the full visual field (MRS90) in static perimetry at Week 52 | Mean retinal sensitivity within the full visual field (MRS90) in static perimetry at Week 52 | Day 1 - Week 52 | 
| Change in functional vision as measured by patient-reported outcomes at Week 52 | Change in functional vision as measured by patient-reported outcomes at Week 52 | Day 1 - Week 52 | 
| Change in visual function as assessed by binocular low luminance visual acuity using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart letter score at Week 52 | Binocular low luminance visual acuity using the ETDRS chart letter score at Week 52 | Day 1 - Week 52 | 
| Change in visual function as assessed by binocular best corrected visual acuity (BCVA) using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart letter score at Week 52 | Binocular BCVA using the ETDRS chart letter score at Week 52 | Day 1 - Week 52 | 
| Safety and tolerability through Week 52 as assessed by: | Number of participants with ocular and non-ocular adverse events Number of participants with abnormalities in Hematologic and Clinical Chemistry parameters | Day 1 - Week 52 |