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

This study is currently recruiting participants. (see Contacts and Locations)
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:
Leber Congenital Amaurosis
Retinal Diseases
Eye Diseases
Eye Diseases, Hereditary processed this record on November 25, 2015