Safety Study of RPE65 Gene Therapy to Treat Leber Congenital Amaurosis

• Sponsor: University College, London (Other)
• Overall Status: Completed
• CT.gov ID: NCT00643747
• Collaborator: Moorfields Eye Hospital NHS Foundation Trust (Other), Targeted Genetics Corporation (Industry)
• Enrollment: 12
• Location: 1
• Arm: 1
• Duration (Months): 95
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of the study is to determine whether gene therapy is safe and effective for the treatment of severe childhood blindness caused by mutations in RPE65.

Condition or Disease	Intervention/Treatment	Phase
Retinal Degeneration	Biological: tgAAG76 (rAAV 2/2.hRPE65p.hRPE65)	Phase 1/Phase 2

Detailed Description

The main objective of the proposed trial is to determine the safety and efficacy subretinal administration of a recombinant adeno-associated viral vector (rAAV 2/2.hRPE65p.hRPE65) at three different dosage levels in individuals with autosomal recessive severe early-onset retinal degeneration due to mutations in RPE65. We have a comprehensive clinical monitoring plan to investigate the safety and efficacy of vector delivery.

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label Dose Escalation Study of an Adeno-associated Virus Vector (AAV2/2-hRPE65p-hRPE65) for Gene Therapy of Severe Early-onset Retinal Degeneration
• Study Start Date: Jan 1, 2007
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A Injection of vector	Biological: tgAAG76 (rAAV 2/2.hRPE65p.hRPE65); Single subretinal injection of vector suspension; up to 3x10e12 vector particles; Other Names: rAAV 2/2.hRPE65p.hRPE65

Outcome Measures

Primary Outcome Measures

1. intraocular inflammation [at intervals up to 12 months]

Secondary Outcome Measures

1. visual function [intervals up to 12 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 5 Years to 30 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Clinical diagnosis of severe early-onset retinal dystrophy confirmed missense mutation(s) in RPE65

Exclusion Criteria:

• Visual acuity in the study eye better than 6/36 Snellen

• Hypertension

• Diabetes mellitus

• Tuberculosis

• Renal impairment

• Immunocompromise

• Osteoporosis

• Gastric ulceration

• Severe affective disorder)

• Pregnancy or lactation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Moorfields Eye Hospital NHS Foundation Trust	London		United Kingdom	EC1V 2PD

Sponsors and Collaborators

• University College, London
• Moorfields Eye Hospital NHS Foundation Trust
• Targeted Genetics Corporation

Investigators

• Study Director: Robin R Ali, PhD, University College, London

Study Documents (Full-Text)

None provided.

More Information

Publications

• Bainbridge JW, Mehat MS, Sundaram V, Robbie SJ, Barker SE, Ripamonti C, Georgiadis A, Mowat FM, Beattie SG, Gardner PJ, Feathers KL, Luong VA, Yzer S, Balaggan K, Viswanathan A, de Ravel TJ, Casteels I, Holder GE, Tyler N, Fitzke FW, Weleber RG, Nardini M, Moore AT, Thompson DA, Petersen-Jones SM, Michaelides M, van den Born LI, Stockman A, Smith AJ, Rubin G, Ali RR. Long-term effect of gene therapy on Leber's congenital amaurosis. N Engl J Med. 2015 May 14;372(20):1887-97. doi: 10.1056/NEJMoa1414221. Epub 2015 May 4.

• Responsible Party: University College, London
• ClinicalTrials.gov Identifier: NCT00643747
• Other Study ID Numbers: 06/061
• First Posted: Mar 26, 2008
• Last Update Posted: Dec 7, 2015
• Last Verified: Dec 1, 2013

• Keywords provided by University College, London: retinal dystrophy; Leber congenital amaurosis; RPE65; gene therapy
• Additional relevant MeSH terms: Retinal Degeneration; Leber Congenital Amaurosis

Study Results

No Results Posted as of Dec 7, 2015