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

Phase 1

Active, not recruiting

• Conditions: Amaurosis of Leber; Retinal Diseases
• Interventions: Genetic: rAAV2-CBSB-hRPE65

• Registration Number: NCT00481546
• Lead Sponsor: University of Pennsylvania

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2007-05-31
• Study First Submitted QC: 2007-05-31
• Study First Posted: 2007-06-01
• Study Start: 2007-07
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-23
• Last Update Posted: 2024-07-24
• Primary Completion: 2026-06
• Study Completion: 2026-06

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 15

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Experimental	rAAV2-CBSB-hRPE65	All clinical trial subjects received the same vector.

Primary Outcome Measures

Name	Time	Method
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.	15 years

Secondary Outcome Measures

Name	Time	Method
Visual function will be quantified prior to and after vector administration in order to determine whether vector administration affects visual function.	15 years

Trial Locations

Locations (2)

Shands Children's Hospital, University of Florida; 🇺🇸 Gainesville, Florida, United States

Scheie Eye Institute, University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States