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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

Tracking Information
First Submitted Date  ICMJE January 12, 2009
First Posted Date  ICMJE January 13, 2009
Last Update Posted Date April 10, 2018
Actual Study Start Date  ICMJE February 1, 2009
Actual Primary Completion Date June 29, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 12, 2009)
The primary outcome measure is ocular and systemic safety of the treatment. [ Time Frame: 3 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 12, 2009)
Visual function, as quantified before and after vector administration. [ Time Frame: 3 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Clinical Trial of Gene Therapy for Leber Congenital Amaurosis Caused by RPE65 Mutations
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Leber Congenital Amaurosis
Intervention  ICMJE 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;
Study Arms  ICMJE Experimental: rAAV2-hRPE65
Intervention: Genetic: rAAV2-hRPE65
Publications *

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 8, 2018)
Original Estimated Enrollment  ICMJE
 (submitted: January 12, 2009)
Actual Study Completion Date  ICMJE January 1, 2017
Actual Primary Completion Date June 29, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 8 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Israel
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00821340
Other Study ID Numbers  ICMJE RPE65-HMO-CTIL
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Hadassah Medical Organization
Study Sponsor  ICMJE Hadassah Medical Organization
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Eyal Banin, MD, PhD Hadassah Medical Organization
PRS Account Hadassah Medical Organization
Verification Date February 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP