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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
49
Single, subretinal administration of AAV5-RPGR
Massachusetts Eye and Ear Institute
Boston, Massachusetts, United States
Kellogg Eye Center
Ann Arbor, Michigan, United States
UPMC Eye Center
Pittsburgh, Pennsylvania, United States
Leeds Teaching Hospitals NHS Trust
Leeds, United Kingdom
Moorfields Eye Hospital NHS Foundation Trust
London, United Kingdom
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.
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)
Time frame: 9 weeks
Improvements in Visual Function as Assessed by Visual Acuity
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.
Time frame: Baseline and Month 6
Improvements in Retinal Function as Assessed by Static Perimetry
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.
Time frame: Baseline and Month 6
Quality of Life Measured by the Low Luminance Questionnaire (LLQ) Emotional Distress Domain Score
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.
Time frame: Baseline and Month 6
Quality of Life Measured by the Low Luminance Questionnaire (LLQ) Extreme Lighting Domain Score
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.
Time frame: Baseline and Month 6
Quality of Life Measured by the Low Luminance Questionnaire (LLQ) General Dim Lighting Domain Score
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.
Time frame: Baseline and Month 6
Quality of Life Measured by the Low Luminance Questionnaire (LLQ) Mobility Domain Score
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.
Time frame: Baseline and Month 6
Quality of Life Measured by the Low Luminance Questionnaire (LLQ) Peripheral Vision Domain Score
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.
Time frame: Baseline and Month 6
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