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

June 29, 2023 updated by: University of Pennsylvania

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

15

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Gainesville, Florida, United States, 32610
        • Shands Children's Hospital, University of Florida
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Scheie Eye Institute, University of Pennsylvania

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

8 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
15 years

Secondary Outcome Measures

Outcome Measure
Time Frame
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
15 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Pennsylvania

Collaborators

National Eye Institute (NEI)

Investigators

  • Principal Investigator: Samuel G. Jacobson, MD, PhD, University of Pennsylvania

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2007

Primary Completion (Estimated)

June 1, 2026

Study Completion (Estimated)

June 1, 2026

Study Registration Dates

First Submitted

May 31, 2007

First Submitted That Met QC Criteria

May 31, 2007

First Posted (Estimated)

June 1, 2007

Study Record Updates

Last Update Posted (Actual)

July 3, 2023

Last Update Submitted That Met QC Criteria

June 29, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Retinal Diseases

Clinical Trials on rAAV2-CBSB-hRPE65

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Togo

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe