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

NCT03252847 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: MGT009
• Study Type: interventional
• Target: 49
• Locations: 2 countries
• Sites: 5

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.

Conditions

X-Linked Retinitis Pigmentosa

Keywords

XLRP RPGR

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Improvements in Visual Function as Assessed by Visual Acuity

  Baseline and Month 6

• Improvements in Retinal Function as Assessed by Static Perimetry

  Baseline and Month 6

• Quality of Life Measured by the Low Luminance Questionnaire (LLQ) Emotional Distress Domain Score

  Baseline and Month 6

• Quality of Life Measured by the Low Luminance Questionnaire (LLQ) Extreme Lighting Domain Score

  Baseline and Month 6

• Quality of Life Measured by the Low Luminance Questionnaire (LLQ) General Dim Lighting Domain Score

  Baseline and Month 6

Study Arms (2)

Phase 1 (Part 1, Dose Escalation)

EXPERIMENTAL

Participants receive one of three doses of AAV5-RPGR

Genetic: AAV5-RPGR

Phase 2 (Part 2; Expansion)

EXPERIMENTAL

Participants receive one of two doses of AAV5-RPGR

Genetic: AAV5-RPGR

Interventions

AAV5-RPGR GENETIC

Single, subretinal administration of AAV5-RPGR

Phase 1 (Part 1, Dose Escalation); Phase 2 (Part 2; Expansion)

Eligibility Criteria

• Age: 5 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• MeiraGTx UK II Ltd: lead
• Syne Qua Non Limited: collaborator
• Bionical Emas: collaborator

Study Sites (5)

Massachusetts Eye and Ear Institute

Boston, Massachusetts, 02114, United States

Location

Kellogg Eye Center

Ann Arbor, Michigan, 48105, United States

Location

UPMC Eye Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Leeds Teaching Hospitals NHS Trust

Leeds, LS9 7TF, United Kingdom

Location

Moorfields Eye Hospital NHS Foundation Trust

London, United Kingdom

Location

Related Publications (1)

• Michaelides M, Besirli CG, Yang Y, DE Guimaraes TAC, Wong SC, Huckfeldt RM, Comander JI, Sahel JA, Shah SM, Tee JJL, Kumaran N, Georgiadis A, Minnick P, Zeldin R, Naylor S, Xu J, Clark M, Anglade E, Wong P, Fleck PR, Fung A, Peluso C, Kalitzeos A, Georgiou M, Ripamonti C, Smith AJ, Ali RR, Forbes A, Bainbridge J. Phase 1/2 AAV5-hRKp.RPGR (Botaretigene Sparoparvovec) Gene Therapy: Safety and Efficacy in RPGR-Associated X-Linked Retinitis Pigmentosa. Am J Ophthalmol. 2024 Nov;267:122-134. doi: 10.1016/j.ajo.2024.05.034. Epub 2024 Jun 12.

  PMID: 38871269 DERIVED

Results Point of Contact

• Title: Program Manager
• Organization: MeiraGTx

ocularinfo@meiragtx.com

+44 (0)20 3866 4320

Study Officials

• James Bainbridge, Prof

  University College, London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Biological

Study Record Dates

• First Submitted: August 1, 2017
• First Posted: August 17, 2017
• Study Start: July 31, 2017
• Primary Completion: November 18, 2021
• Study Completion: November 18, 2021
• Last Updated: January 8, 2025
• Results First Posted: January 8, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (3); GB (2)