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Phase I Trial of Gene Vector to Patients With Retinal Disease Due to RPE65 Mutations (LCA)

This study is ongoing, but not recruiting participants.
National Eye Institute (NEI)
Information provided by (Responsible Party):
University of Pennsylvania Identifier:
First received: May 31, 2007
Last updated: August 18, 2016
Last verified: August 2016

May 31, 2007
August 18, 2016
July 2007
June 2026   (Final data collection date for primary outcome measure)
The primary safety endpoint in this trial is the standard ocular examination. Toxicity will also be assessed by measurement of vision, hematology and serum chemistries, assays for vector genomes, reported subject history of symptoms and adverse events. [ Time Frame: 15 years ]
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Complete list of historical versions of study NCT00481546 on Archive Site
Visual function will be quantified prior to and after vector administration in order to determine whether vector administration affects visual function. [ Time Frame: 15 years ]
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Phase I Trial of Gene Vector to Patients With Retinal Disease Due to RPE65 Mutations
Phase I Trial of Ocular Subretinal Injection of a Recombinant Adeno-Associated Virus (rAAV2-CBSB-hRPE65) Gene Vector to Patients With Retinal Disease Due to RPE65 Mutations (Clinical Trials of Gene Therapy for Leber Congenital Amaurosis)

A recombinant adeno-associated virus serotype 2 (rAAV2) vector has been altered to carry the human RPE65 (hRPE65) gene. This vector has been shown to restore vision in animal models that resemble human RPE65-associated Leber congenital amaurosis (LCA), an incurable retinal degeneration that causes severe vision loss. The proposed study is an open label, Phase I clinical trial of subretinal rAAV2-CBSB-hRPE65 administration to individuals with RPE65-associated retinal disease. Five cohorts will be included in this trial. Cohorts 1, 2 and 4 will consist of individuals 18 years of age and older. Cohorts 3 and 5 will consist of individuals between the ages of 8 and 17, inclusive. Enrollment in Cohorts 3 and 5 will begin only after confirming the safety of rAAV2-CBSB-hRPE65 administration in the older groups of participants. This trial will lead to a greater understanding of the safety and thereby potential value of gene transfer in RPE65-associated retinal disease and will have implications for other forms of retinal degenerative disease amenable to this type of intervention.

The goal of this clinical trial is to determine the safety of uniocular subretinal administration of rAAV2-CBSB-hRPE65 in individuals with RPE65-associated retinal disease. Ocular and systemic toxicity will be assessed prior to and following vector administration to determine if there are adverse changes that may be associated with vector administration.

Not Provided
Phase 1
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Amaurosis of Leber
  • Retinal Diseases
Genetic: rAAV2-CBSB-hRPE65
One or two, uniocular, subretinal injections; relative doses: 0.3X (Cohort 1), 0.6X (Cohort 2), 0.45X (Cohort 3), 0.9X (Cohorts 4 and 5)
Experimental: Experimental
All clinical trial subjects received the same vector.
Intervention: Genetic: rAAV2-CBSB-hRPE65

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Active, not recruiting
June 2026
June 2026   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • RPE65-associated retinal disease (two disease-causing RPE65 mutations);
  • Clinical diagnosis of Leber congenital amaurosis (LCA)/early-onset retinal degeneration (EORD) and of severely impaired visual and retinal function, and best corrected visual acuity of 20/40 or worse in the study eye;
  • Ability to perform tests of visual and retinal function;
  • Visible photoreceptor layer on a standard OCT scan;
  • Good general health;
  • Ability to comply with research procedures;
  • Specific for Cohorts 1, 2 and 4: 18 years of age and older;
  • Specific for Cohorts 3 and 5: Between 8 and 17 years of age, inclusive.

Exclusion Criteria:

  • AAV antibody titers greater than two standard deviations above normal at baseline;
  • Humoral immune deficiency as evidenced by low tetanus toxoid IgG antibody titers;
  • Pre-existing eye conditions that would preclude the planned surgery or interfere with the interpretation of study endpoints or surgical complications;
  • Complicating systemic diseases;
  • Use of anti-platelet agents that may alter coagulation within 7 days prior to study agent administration;
  • Use of immunosuppressive medications;
  • Pregnancy or breastfeeding;
  • Individuals (males and females) of childbearing potential who are unwilling to use effective contraception;
  • Any condition that would prevent a subject from completing follow-up examinations during the course of the study;
  • Any condition that makes the subject unsuitable for the study;
  • Current, or recent participation, in any other research protocol involving investigational agents or therapies;
  • Recent receipt of an investigational biologic therapeutic agent.
Sexes Eligible for Study: All
8 Years and older   (Child, Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
United States
Grant: 1 U10 EY017280-01;
UP IRB: 804582;
UP IBC: 06-105;
UF GCRC: 675;
UF IBC RD: 2795;
WIRB: 20061300
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University of Pennsylvania
University of Pennsylvania
National Eye Institute (NEI)
Principal Investigator: Samuel G. Jacobson, MD, PhD University of Pennsylvania
University of Pennsylvania
August 2016

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