Safety Study of RPE65 Gene Therapy to Treat Leber Congenital Amaurosis

Retinal Degeneration Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00643747
• Other study ID #: 06/061
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: March 20, 2008
• Last updated: December 4, 2015
• Start date: January 2007
• Est. completion date: December 2014

Study information

• Verified date: December 2013
• Source: University College, London
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 5 Years to 30 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leber Congenital Amaurosis
• Retinal Degeneration

Intervention

Biological:
• tgAAG76 (rAAV 2/2.hRPE65p.hRPE65)
Single subretinal injection of vector suspension; up to 3x10e12 vector particles

Locations

Country	Name	City	State
United Kingdom	Moorfields Eye Hospital NHS Foundation Trust	London

Sponsors (3)

Lead Sponsor	Collaborator
University College, London	Moorfields Eye Hospital NHS Foundation Trust, Targeted Genetics Corporation

Country where clinical trial is conducted

United Kingdom, 

References & Publications (2)

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. — View 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 functi — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	intraocular inflammation		at intervals up to 12 months	Yes
Secondary	visual function		intervals up to 12 months	Yes