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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00821340
Recruitment Status : Completed
First Posted : January 13, 2009
Last Update Posted : April 10, 2018
Information provided by (Responsible Party):
Hadassah Medical Organization

Brief Summary:
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 or disease Intervention/treatment Phase
Leber Congenital Amaurosis Genetic: rAAV2-hRPE65 Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (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
Actual Study Start Date : February 1, 2009
Actual Primary Completion Date : June 29, 2016
Actual Study Completion Date : January 1, 2017

Arm Intervention/treatment
Experimental: rAAV2-hRPE65 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;

Primary Outcome Measures :
  1. The primary outcome measure is ocular and systemic safety of the treatment. [ Time Frame: 3 years ]

Secondary Outcome Measures :
  1. Visual function, as quantified before and after vector administration. [ Time Frame: 3 years ]

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   8 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00821340

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Hadassah Medical Organization
Jerusalem, Israel, 91120
Sponsors and Collaborators
Hadassah Medical Organization
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Principal Investigator: Eyal Banin, MD, PhD Hadassah Medical Organization

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Responsible Party: Hadassah Medical Organization Identifier: NCT00821340    
Other Study ID Numbers: RPE65-HMO-CTIL
First Posted: January 13, 2009    Key Record Dates
Last Update Posted: April 10, 2018
Last Verified: February 2010
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hadassah Medical Organization:
Leber congenital amaurosis
RPE65-associated Leber congenital amaurosis
Retinal disease due to RPE65 mutations
Additional relevant MeSH terms:
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Retinal Diseases
Leber Congenital Amaurosis
Eye Diseases
Vision Disorders
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Eye Diseases, Hereditary