Gene Therapy for X-linked Retinitis Pigmentosa (XLRP) - Retinitis Pigmentosa GTPase Regulator (RPGR)
- Conditions
- X-Linked Retinitis Pigmentosa
- Interventions
- Genetic: AAV2/5-RPGR
- Registration Number
- NCT03252847
- Lead Sponsor
- MeiraGTx UK II Ltd
- Brief Summary
Phase 1 of the study is a dose escalation of the subretinal administration of AAV5-hRKp.RPGR vector to assess the safety of this vector in participants with XLRP caused by mutations in RPGR. Participants enrolled in Phase 1 were assigned to a dose group based on when they enrolled (i.e., sequential assignment).
Phase 2 of the study is a cohort expansion of the subretinal administration of AAV5-hRKp.RPGR vector to assess the safety and efficacy of this vector in participants with XLRP caused by mutations in RPGR. Participants enrolled in Phase 2 were randomized to immediate or deferred treatment.
- Detailed Description
This is an open-label phase 1/2 dose-escalation and cohort expansion trial to determine the safety and efficacy of subretinal administration of AAV5-hRKp.RPGR vector in participants with XLRP caused by mutations in RPGR.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 49
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 2 (Part 2; Expansion) AAV2/5-RPGR Participants receive one of two doses of AAV2/5-RPGR Phase 1 (Part 1, Dose Escalation) AAV2/5-RPGR Participants receive one of three doses of AAV2/5-RPGR
- Primary Outcome Measures
Name Time Method Number of Participants Meeting the Primary Outcome Defined as Any of the Below Events Occurring During the 9 Weeks Following Administration, at Least Possibly Related to the Advanced Therapy Investigational Medicinal Product (ATIMP), Not Surgery Alone. 9 weeks The primary outcome is defined as any of the below occurring during the 9 weeks following administration, at least possibly related to the Advanced Therapy Investigational Medicinal Product (ATIMP), not surgery alone:
* Reduction in visual acuity by 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters or more
* Severe unresponsive inflammation
* Infective endophthalmitis
* Ocular malignancy
* Grade III or above non-ocular Suspected Unexpected Serious Adverse Reaction (SUSAR)
- Secondary Outcome Measures
Name Time Method Improvements in Visual Function as Assessed by Visual Acuity Baseline and Month 6 Change from baseline to Week 26 in best corrected visual acuity (BCVA) using Early Treatment Diabetic Retinopathy Study (ETDRS) chart letter score. The direction of improvement from baseline is an increase in the number of ETDRS letters read over time.
Improvements in Retinal Function as Assessed by Static Perimetry Baseline and Month 6 The number of responders in point-by-point data in Static Perimetry within the full visual field over time.
A responder at a single time point is defined as a participant with at least 5 of the same loci with ≥7 dB improvement from baseline at the specific time point and one time point prior.Quality of Life Measured by the Low Luminance Questionnaire (LLQ) Emotional Distress Domain Score Baseline and Month 6 Change from baseline to Week 26 in LLQ Emotional Distress Domain Score in adults. LLQ uses a scale from 0 to 100, with higher scores reflecting less impairment. A positive change from baseline reflects improvement, and a negative reflects worsening.
Quality of Life Measured by the Low Luminance Questionnaire (LLQ) Extreme Lighting Domain Score Baseline and Month 6 Change from baseline to Week 26 in LLQ Extreme Lighting Domain Score in adults. LLQ uses a scale from 0 to 100, with higher scores reflecting less impairment. A positive change from baseline reflects improvement, and a negative reflects worsening.
Quality of Life Measured by the Low Luminance Questionnaire (LLQ) General Dim Lighting Domain Score Baseline and Month 6 Change from baseline to Week 26 in LLQ General Dim Lighting Domain score in adults. LLQ uses a scale from 0 to 100, with higher scores reflecting less impairment. A positive change from baseline reflects improvement, and a negative reflects worsening.
Quality of Life Measured by the Low Luminance Questionnaire (LLQ) Mobility Domain Score Baseline and Month 6 Change from baseline to Week 26 in LLQ Mobility Domain Score in adults. LLQ uses a scale from 0 to 100, with higher scores reflecting less impairment. A positive change from baseline reflects improvement, and a negative reflects worsening.
Quality of Life Measured by the Low Luminance Questionnaire (LLQ) Peripheral Vision Domain Score Baseline and Month 6 Change from baseline to Week 26 in LLQ Peripheral Vision Domain Score in adults. LLQ uses a scale from 0 to 100, with higher scores reflecting less impairment. A positive change from baseline reflects improvement, and a negative reflects worsening.
Trial Locations
- Locations (5)
Kellogg Eye Center
🇺🇸Ann Arbor, Michigan, United States
Massachusetts Eye and Ear Institute
🇺🇸Boston, Massachusetts, United States
Leeds Teaching Hospitals NHS Trust
🇬🇧Leeds, United Kingdom
UPMC Eye Center
🇺🇸Pittsburgh, Pennsylvania, United States
Moorfields Eye Hospital NHS Foundation Trust
🇬🇧London, United Kingdom