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Safety Study of RPE65 Gene Therapy to Treat Leber Congenital Amaurosis

Primary Purpose

Retinal Degeneration

Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
tgAAG76 (rAAV 2/2.hRPE65p.hRPE65)
Sponsored by
University College, London
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Retinal Degeneration focused on measuring retinal dystrophy, Leber congenital amaurosis, RPE65, gene therapy

Eligibility Criteria

5 Years - 30 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Moorfields Eye Hospital NHS Foundation Trust

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

A

Arm Description

Injection of vector

Outcomes

Primary Outcome Measures

intraocular inflammation

Secondary Outcome Measures

visual function

Full Information

First Posted
March 20, 2008
Last Updated
December 4, 2015
Sponsor
University College, London
Collaborators
Moorfields Eye Hospital NHS Foundation Trust, Targeted Genetics Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT00643747
Brief Title
Safety Study of RPE65 Gene Therapy to Treat Leber Congenital Amaurosis
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 Type
Interventional

2. Study Status

Record Verification Date
December 2013
Overall Recruitment Status
Completed
Study Start Date
January 2007 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
December 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University College, London
Collaborators
Moorfields Eye Hospital NHS Foundation Trust, Targeted Genetics Corporation

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Retinal Degeneration
Keywords
retinal dystrophy, Leber congenital amaurosis, RPE65, gene therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
A
Arm Type
Experimental
Arm Description
Injection of vector
Intervention Type
Biological
Intervention Name(s)
tgAAG76 (rAAV 2/2.hRPE65p.hRPE65)
Other Intervention Name(s)
rAAV 2/2.hRPE65p.hRPE65
Intervention Description
Single subretinal injection of vector suspension; up to 3x10e12 vector particles
Primary Outcome Measure Information:
Title
intraocular inflammation
Time Frame
at intervals up to 12 months
Secondary Outcome Measure Information:
Title
visual function
Time Frame
intervals up to 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
5 Years
Maximum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robin R Ali, PhD
Organizational Affiliation
University College, London
Official's Role
Study Director
Facility Information:
Facility Name
Moorfields Eye Hospital NHS Foundation Trust
City
London
ZIP/Postal Code
EC1V 2PD
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
25938638
Citation
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.
Results Reference
background
PubMed Identifier
18441371
Citation
Bainbridge JW, Smith AJ, Barker SS, Robbie S, Henderson R, Balaggan K, Viswanathan A, Holder GE, Stockman A, Tyler N, Petersen-Jones S, Bhattacharya SS, Thrasher AJ, Fitzke FW, Carter BJ, Rubin GS, Moore AT, Ali RR. Effect of gene therapy on visual function in Leber's congenital amaurosis. N Engl J Med. 2008 May 22;358(21):2231-9. doi: 10.1056/NEJMoa0802268. Epub 2008 Apr 27.
Results Reference
result
PubMed Identifier
26605849
Citation
Ripamonti C, Henning GB, Robbie SJ, Sundaram V, van den Born LI, Casteels I, de Ravel TJ, Moore AT, Smith AJ, Bainbridge JW, Ali RR, Stockman A. Spectral sensitivity measurements reveal partial success in restoring missing rod function with gene therapy. J Vis. 2015;15(15):20. doi: 10.1167/15.15.20.
Results Reference
derived

Learn more about this trial

Safety Study of RPE65 Gene Therapy to Treat Leber Congenital Amaurosis

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