Follow-up 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)

Official Title
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Follow-up 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 4e11
* Biological: Genetic: AAV5-RPGR 2e11


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: 66 Patients randomised in MGT-RPGR-021. 44 patients randomised to Immediate treatment arm. 22 patients randomised to the deferred arm. These patients will be treated in MGT-RPGR-022. All patients to be followed for 60 months.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Deferred treatment from MGT-RPGR-021 4e11<br>Deferred treatment | Biological: Genetic: AAV5-RPGR 4e11<br>* Bilateral, subretinal administration of AAV5-RPGR - deferred treatment group<br>|
| Active Comparator: Already treated in MGT-RPGR-021<br>Already treated | Biological: Genetic: AAV5-RPGR 4e11<br>* Bilateral, subretinal administration of AAV5-RPGR - deferred treatment group<br>Biological: Genetic: AAV5-RPGR 2e11<br>* Bilateral, subretinal administration of AAV5-RPGR - deferred treatment group<br>|
| Experimental: Deferred treatment from MGT-RPGR-021 2e11<br>Deferred treatment | Biological: Genetic: AAV5-RPGR 2e11<br>* Bilateral, subretinal administration of AAV5-RPGR - deferred treatment group<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in vision-guided mobility assessment (VMA), as measured by the ability of the participant to navigate through a VMA maze, after bilateral subretinal delivery of AAV5-hRKp.RPGR | Change from baseline in vision-guided mobility assessment (VMA), as measured by the ability of the participant to navigate through a VMA maze, after bilateral subretinal delivery of AAV5-hRKp.RPGR | Day 1 - Month 60 | 
| Safety and tolerability of bilateral treatment through Month 60 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 - Month 60 | 

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) | Mean retinal sensitivity within the central 10 degrees (MRS10) | Day 1 - Month 60 | 
| Change in retinal function as assessed by pointwise responder in full visual field | Pointwise responder in full visual field | Day 1 - Month 60 | 
| Change in retinal function as assessed by pointwise responder in the central 30-degree visual field | Pointwise responder in the central 30-degree visual field | Day 1 - Month 60 | 
| Change in retinal function as assessed by mean retinal sensitivity within the full visual field (MRS90) | Mean retinal sensitivity within the full visual field (MRS90) | Day 1 - Month 60 | 
| Change in functional vision as measured by patient-reported outcomes | Change in functional vision as measured by patient-reported outcomes | Day 1 - Month 60 | 
| Change in visual function as assessed by binocular low luminance visual acuity using the Early Treatment Diabetic Retinopathy (ETDRS) chart letter score | Binocular low luminance visual acuity using the ETDRS chart letter score | Day 1 - Month 60 | 
| Change in visual function as assessed by binocular best corrected visual acuity (BCVA) using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart letter score | Binocular BCVA using the ETDRS chart letter score | Day 1 - Month 60 |