A Clinical Trial Evaluating the Safety and Efficacy of a Single Subretinal Injection of AGTC-501 in Participants With X-linked Retinitis Pigmentosa Caused by RPGR Mutations

Study Overview
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Brief Summary
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This study will evaluate and compare the safety, efficacy, and tolerability of 2 doses of a recombinant adeno-associated virus vector (AGTC-501) to an untreated control group in male patients with X-linked retinitis pigmentosa caused by RPGR mutations.

Detailed Description
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This Phase 2/3 study is a randomized, controlled, masked, multi-center study evaluating and comparing 2 doses of AGTC-501 to an untreated control group. A single subretinal injection of AGTC-501 Dose 1(low dose) or Dose 2(high dose) will be administered in subjects in 2 treatment groups (N= 42), while subjects in the untreated control group (N= 21) will be followed and evaluated up to Month 12, after which they will be eligible to receive treatment with AGTC-501 Dose 2. Approximately 63 eligible male subjects between 8 and 50 years of age (inclusive) will be randomized in a 1:1:1 ratio to 1 of 3 groups (low dose, high dose, untreated control).

Official Title
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A Phase 2/3, Randomized, Controlled, Masked, Multi-center Study to Evaluate the Efficacy, Safety and Tolerability of Two Doses of AGTC-501, a Recombinant Adeno-associated Virus Vector Expressing RPGR (rAAV2tYF-GRK1-RPGR), Compared to an Untreated Control Group in Male Subjects With X-linked Retinitis Pigmentosa Confirmed by a Pathogenic Variant in the RPGR Gene

Conditions
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X-Linked Retinitis Pigmentosa

Intervention / Treatment
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* Biological: rAAV2tYF-GRK1-hRPGRco


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males between the ages of 8-50 years old with a clinical diagnosis of XLRP with a confirmed RPGR mutation who also meet the other requirements of the study. Have at least one documented pathogenic or likely pathogenic variant in the RPGR gene within exons 1-14 and/or ORF15 Have a BCVA no better than 75 letters (20/32) and no worse than 35 letters (20/200) in the study eye based on an Early Treatment of Diabetic Retinopathy Study (ETDRS) chart at each screening visit Exclusion Criteria: - Have other known retinal disease mutations or previously received an AAV gene therapy product, as well as being unable or unwilling to meet the requirements of the study.

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 50 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects are randomized in a 1:1:1 ratio to 1 of 3 groups (low dose, high dose, untreated). After 12 months, subjects in the untreated group are eligible to receive the high dose of AGTC-501.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1: Low Dose<br>Male subjects 8-50 years of age treated by subretinal injection with the low dose of AGTC-501 | Biological: rAAV2tYF-GRK1-hRPGRco<br>* Adeno-associated virus vector expressing a human RPGR gene<br>* Other names: AGTC-501;|
| Active Comparator: Group 2: High Dose<br>Male subjects 8-50 years of age treated by subretinal injection with the high dose of AGTC-501 | Biological: rAAV2tYF-GRK1-hRPGRco<br>* Adeno-associated virus vector expressing a human RPGR gene<br>* Other names: AGTC-501;|
| Other: Group 3: Control<br>Male subjects 8-50 years of age in the untreated control group. Subjects randomized to the untreated control group will be followed for a minimum of 12 months. After this time, they will be treated by subretinal injection with the high dose of AGTC-501. | Biological: rAAV2tYF-GRK1-hRPGRco<br>* Adeno-associated virus vector expressing a human RPGR gene<br>* Other names: AGTC-501;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The difference in the proportion of responding eyes between treated and control eyes in low dose group and high dose group |  | Day 0 - Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| - Proportion of responding eyes in treated study eyes in the low dose group and high dose group versus untreated control eyes, as measured by mobility test score change |  | Day 0 - Month 12 | 
| - Proportion of responding eyes in treated eyes versus control eyes in the low dose and high dose group measured by visual function assessments |  | Day 0 - Month 12 | 
| - Difference in mean change from baseline in Visual Acuity in treated eyes versus control eyes in the low dose and high dose groups |  | Day 0 - Month 12 | 
| - Difference in mean change from baseline in the EZ area, as measured by SD-OCT, in treated study eyes in the low dose group and high dose group versus untreated control study eyes |  | Day 0 - Month 12 | 
| Changes from baseline in quality of life questionnaire responses |  | Day 0 - Month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AAV, XLRP, retinal degeneration, RPGR, adeno-associated virus, gene therapy