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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 23, 2017
Last verified: August 2017

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.

Condition Intervention Phase
Amaurosis of Leber Retinal Diseases Genetic: rAAV2-CBSB-hRPE65 Phase 1

Study Type: Interventional
Study Design: 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-CBSB-hRPE65) Gene Vector to Patients With Retinal Disease Due to RPE65 Mutations (Clinical Trials of Gene Therapy for Leber Congenital Amaurosis)

Resource links provided by NLM:

Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 15
Study Start Date: July 2007
Estimated Study Completion Date: June 2026
Estimated Primary Completion Date: June 2026 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Experimental
All clinical trial subjects received the same vector.
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)


Ages Eligible for Study:   8 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.
  Contacts and Locations
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Please refer to this study by its identifier: NCT00481546

United States, Florida
Shands Children's Hospital, University of Florida
Gainesville, Florida, United States, 32610
United States, Pennsylvania
Scheie Eye Institute, University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
University of Pennsylvania
National Eye Institute (NEI)
Principal Investigator: Samuel G. Jacobson, MD, PhD University of Pennsylvania
  More Information


Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: University of Pennsylvania Identifier: NCT00481546     History of Changes
Other Study ID Numbers: 547233
Grant: 1 U10 EY017280-01;
UP IRB: 804582;
UP IBC: 06-105;
UF GCRC: 675;
UF IBC RD: 2795;
WIRB: 20061300
Study First Received: May 31, 2007
Last Updated: August 23, 2017

Keywords provided by University of Pennsylvania:
Leber congenital amaurosis
Retinal disease due to RPE65 mutations
RPE65-associated Leber congenital amaurosis

Additional relevant MeSH terms:
Retinal Diseases
Leber Congenital Amaurosis
Eye Diseases
Vision Disorders
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Eye Diseases, Hereditary processed this record on September 21, 2017