Gene Therapy for X-linked Retinitis Pigmentosa (XLRP) - Retinitis Pigmentosa GTPase Regulator (RPGR)

An Open Label, Multi-centre, Phase I/II Dose Escalation Trial of a Recombinant Adeno-associated Virus Vector (AAV2/5-hRKp.RPGR) for Gene Therapy of Adults and Children With X-linked Retinitis Pigmentosa Owing to Defects in Retinitis Pigmentosa GTPase Regulator (RPGR)

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.

Study Overview

• Status: Completed
• Conditions: X-Linked Retinitis Pigmentosa
• Intervention / Treatment: Genetic: AAV5-RPGR

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.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Leeds, United Kingdom, LS9 7TF
    • Leeds Teaching Hospitals NHS Trust
  • London, United Kingdom
    • Moorfields Eye Hospital NHS Foundation Trust
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts Eye and Ear Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • Kellogg Eye Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Eye Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key inclusion Criteria:

• Males aged 5 years or older
• Have X-linked retinitis pigmentosa confirmed by a retinal specialist (CI or PI)

Key exclusion Criteria:

• Have participated in another research study involving an investigational medicinal therapy for ocular disease within the last 6 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1 (Part 1, Dose Escalation); Participants receive one of three doses of AAV5-RPGR	Genetic: AAV5-RPGR; Single, subretinal administration of AAV5-RPGR
Experimental: Phase 2 (Part 2; Expansion); Participants receive one of two doses of AAV5-RPGR	Genetic: AAV5-RPGR; Single, subretinal administration of AAV5-RPGR

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	9 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	Baseline and Month 6

Collaborators and Investigators

• Sponsor: MeiraGTx UK II Ltd
• Collaborators: Syne Qua Non Limited; Bionical Emas
• Investigators: Principal Investigator: James Bainbridge, Prof, University College, London

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2017
• Primary Completion (Actual): November 18, 2021
• Study Completion (Actual): November 18, 2021

Study Registration Dates

• First Submitted: August 1, 2017
• First Submitted That Met QC Criteria: August 16, 2017
• First Posted (Actual): August 17, 2017

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 17, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: XLRP RPGR
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Eye Diseases; Eye Diseases, Hereditary; Retinal Diseases; Retinal Dystrophies; Retinal Degeneration; Retinitis; Retinitis Pigmentosa
• Other Study ID Numbers: MGT009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No