Clinical trial NCT00643747: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Retinal Degeneration
Keywords: retinal dystrophy
Leber congenital amaurosis
RPE65
gene therapy
Lead sponsor: University College, London
Sponsor class: OTHER
Collaborators: name: Moorfields Eye Hospital NHS Foundation Trust
name: Targeted Genetics Corporation
First posted: 2008-03-26
Enrollment: 12
Sex: ALL
Minimum age (years): 5
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: intraocular inflammation
timeFrame: at intervals up to 12 months
Secondary outcomes:
measure: visual function
timeFrame: intervals up to 12 months
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Moorfields Eye Hospital NHS Foundation Trust
Study officials:
affiliation: University College, London
name: Robin R Ali, PhD
role: STUDY_DIRECTOR
References:
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.
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.
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.