Safety and Efficacy of rAAV2tYF-GRK1-RPGR in Subjects With X-linked Retinitis Pigmentosa Caused by RPGR Mutations

Safety and Efficacy of rAAV2tYF-GRK1-RPGR in Subjects With X-linked Retinitis Pigmentosa Caused by RPGR Mutations

Brief Summary:
This study will evaluate the safety and efficacy of a recombinant adeno-associated virus vector (rAAV2tYF-GRK1-RPGR) in patients with X-linked retinitis pigmentosa caused by RPGR mutations. Approximately 42 participants will be enrolled in 2 study phases, 30 participants in the phase 1/2 dose escalation portion of the study, and 12 participants in the phase 2 dose expansion portion.

Detailed Description:
This study includes a non-randomized, open-label, Phase 1/2 dose escalation portion, and a Phase 2 randomized, controlled, masked dose expansion portion.

Approximately 30 participants will be enrolled into the dose escalation portion of the study. Each participant will receive the study agent by subretinal injection in one eye on a single occasion. Enrollment will begin with the lowest dose and will proceed to higher doses only after review of safety data by a Data and Safety Monitoring Committee (DSMC). Within groups 1 through 3 and 5 and 6, enrollment of participants will be staggered by at least 2 weeks to allow adequate time for review of safety information by the investigators and sponsor. Within Group 4, enrollment of the first 3 pediatric participants will be staggered by at least 2 weeks to allow adequate time for review of safety information by the investigators and sponsor. Study agent administration will occur on Day 0. There are a total of 15 visits over approximately 36 months, and long-term follow-up evaluations annually at years 4 and 5.

After the phase 1/2 portion of the study is completed, approximately 12 participants, who were not part of the Phase 1/2 portion of the study, will be enrolled into the dose expansion portion of the study. These participants will be randomized in a 1:1 ratio to 1 of 2 treatment groups (i.e., Group 1 [low dose, 300 μL containing 1.2 x 1011 vg/mL] and Group 2 [high dose, 300 μL containing 1.1 x 1012 vg/mL]). Each participant will receive the assigned dose of AGTC-501 in one eye on a single occasion. Randomization to dose groups will be stratified by age (8-17 years, 18-50 years). To minimize bias in the assessment and reporting of outcomes, both the investigators and the study subjects will be masked to the dose of AGTC-501 received. Study agent administration will occur on Day 0. There are a total of 15 visits over approximately 24 months, and long-term follow-up evaluations annually at years 3, 4 and 5.

Safety will be measured by the number and proportion of participants experiencing ocular and non-ocular adverse events and abnormal clinically relevant hematology and clinical chemistry parameters. Efficacy will be measured by evaluation of changes in visual structure, function, and quality of life.


Study Type: Interventional (Clinical Trial)
Estimated Enrollment: 42 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: An Open-Label Dose Escalation Study to Evaluate the Safety and Efficacy of AGTC-501 (rAAV2tYF-GRK1-RPGR) in Subjects With X-linked Retinitis Pigmentosa Caused by RPGR Mutations
Actual Study Start Date: April 16, 2018
Estimated Primary Completion Date: August 2022
Estimated Study Completion Date: August 2026

Arm:
- Experimental: Group 1: Phase 1/2 Dose Escalation
- Experimental: Group 2: Phase 1/2 Dose Escalation and Low Dose Group Phase 2 Dose Expansion
- Experimental: Group 3 and Group 4 Phase 1/2 Dose Escalation
- Experimental: Group 5 Phase 1/2 Dose Escalation and High Dose Group Phase 2 Dose Expansion
- Experimental: Group 6 Phase 1/2 Dose Escalation

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