Clinical Trial of Gene Therapy for Leber Congenital Amaurosis Caused by RPE65 Mutations

This study is currently recruiting participants.
Verified February 2010 by Hadassah Medical Organization
Information provided by:
Hadassah Medical Organization Identifier:
First received: January 12, 2009
Last updated: March 1, 2010
Last verified: February 2010

The purpose of this clinical trial is to examine the safety of gene therapy for Lebers Congenital Amaurosis (LCA) caused by RPE65 mutations using a recombinant adeno-associated virus serotype 2 (rAAV2) vector carrying the human RPE65 (hRPE65) gene. Recently, three independent short-term gene therapy studies in humans with LCA due to RPE65 mutations were published, suggesting that subretinal delivery of rAAV virus carrying the RPE65 gene is safe. As a secondary outcome, improvement in visual function was observed in seven of the first nine treated patients. The proposed study is a similar open label, Phase I clinical trial of uniocular subretinal rAAV2-hRPE65 administration to individuals with RPE65-associated retinal disease. Two cohorts of three subjects each and one cohort of four subjects will be included in this trial. Cohort 1 and 2 will consist of individuals 18 years of age and older and Cohorts 3 will consist of individuals 8 years of age and older. In cohort 2, a larger volume of vector will be administered. Enrollment in Cohort 3 will begin only after confirming the safety of rAAV2-hRPE65 administration in the older group of participants.

Condition Intervention Phase
Leber Congenital Amaurosis
Genetic: rAAV2-hRPE65
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Trial of Ocular Subretinal Injection of a Recombinant Adeno-Associated Virus (rAAV2-hRPE65) Gene Vector to Patients With Retinal Disease Due to RPE65 Mutations

Resource links provided by NLM:

Further study details as provided by Hadassah Medical Organization:

Primary Outcome Measures:
  • The primary outcome measure is ocular and systemic safety of the treatment. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Visual function, as quantified before and after vector administration. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 10
Study Start Date: January 2010
Estimated Study Completion Date: January 2017
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Intervention Details:
    Genetic: rAAV2-hRPE65
    Uniocular subretinal injections; relative doses: Cohort 1 - basic (lowest) viral dose; Cohort 2 - higher (1.5 times basic) viral dose; Cohort 3 - patients 8-17 years of age will receive basic viral dose; patients 18 years of age and over will receive higher dose;

Ages Eligible for Study:   8 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Retinal disease caused by homozygous or compound heterozygote RPE65 mutations;
  • Clinical diagnosis of Leber congenital amaurosis (LCA) with severely impaired visual and retinal function, and best corrected visual acuity of 20/50 or worse in the study eye;
  • Ability to perform tests of visual and retinal function;
  • Good general health;
  • Ability to comply with research procedures;
  • Specific for Cohort 1 and 2: 18 years of age and older;
  • Specific for Cohort 3: Over 8 years of age;

Exclusion Criteria:

  • Immune deficiency or use of immunosuppressive medications;
  • Pre-existing eye conditions that would preclude the planned surgery or interfere with the interpretation of study endpoints (for example, glaucoma or ocular media opacities);
  • Complicating systemic diseases;
  • Impaired coagulation or use of anti-platelet agents within 7 days prior to study agent administration;
  • Pregnancy or breastfeeding;
  • Individuals (males and females) of childbearing potential who are unwilling to use effective contraception for 1 year following agent administration and barrier contraception for 3 months following agent administration;
  • Any other condition that would prevent a subject from completing follow-up examinations during the course of the study;
  • Any other condition that, in the opinion of the investigator, makes the subject unsuitable for the study;
  • Current or recent participation in any other research protocol involving investigational agents or therapies, including recent (within past 6 months) receipt of an investigational biologic therapeutic agent.

Subjects will not be excluded based on their gender, race or ethnicity.

  Contacts and Locations
Please refer to this study by its identifier: NCT00821340

Hadassah Medical Organization Recruiting
Jerusalem, Israel, 91120
Contact: Devora Marks Ohana    00 972 2 6776324   
Principal Investigator: Eyal Banin, MD, PhD         
Sponsors and Collaborators
Hadassah Medical Organization
Principal Investigator: Eyal Banin, MD, PhD Hadassah Medical Organization
  More Information


Responsible Party: Eyal Banin, MD, PhD, Hadassah Medical Organization, Jerusalem, Israel Identifier: NCT00821340     History of Changes
Other Study ID Numbers: RPE65-HMO-CTIL
Study First Received: January 12, 2009
Last Updated: March 1, 2010
Health Authority: Israel: Ministry of Health

Keywords provided by Hadassah Medical Organization:
Leber congenital amaurosis
RPE65-associated Leber congenital amaurosis
Retinal disease due to RPE65 mutations

Additional relevant MeSH terms:
Retinal Diseases
Leber Congenital Amaurosis
Eye Diseases
Eye Diseases, Hereditary
Vision Disorders
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms processed this record on April 21, 2014