Phase 1 Follow-on Study of AAV2-hRPE65v2 Vector in Subjects With Leber Congenital Amaurosis (LCA) 2

September 25, 2023 updated by: Spark Therapeutics

A Follow-On Study to Evaluate the Safety of Re-Administration of Adeno-Associated Viral Vector Containing the Gene for Human RPE65 [AAV2-hRPE65v2] to the Contralateral Eye in Subjects With Leber Congenital Amaurosis (LCA) Previously Enrolled in a Phase 1 Study

The study is a follow-on to a Phase 1 dose-escalation and safety study.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

The study is a follow-on to a Phase 1 dose-escalation and safety study (closed to enrollment as of June 2009). Up to twelve adults and children with a molecular diagnosis of biallelic RPE65 mutations, who have participated in the earlier Phase 1 study, and who meet all study eligibility criteria, will receive AAV2-hRPE65v2 vector in the previously uninjected, contralateral eye to evaluate the safety of bilateral, sequential subretinal administration of AAV2-hRPE65v2.

Study Type

Interventional

Enrollment (Estimated)

12

Phase

  • Phase 2
  • 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
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • The Children's Hospital of Philadelphia

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:

  • Prior participation in Phase 1 study with unilateral, subretinal administration of AAV2-hRPE65v2.
  • Visual acuity equal to or greater than light perception.
  • Sufficient viable retinal cells in contralateral, previously uninjected eye, as determined by non-invasive means, such as optical coherence tomography (OCT) and/or ophthalmoscopy. Must have either: 1) an area of retina within the posterior pole of > 100 µm shown on OCT; 2) ≥ 3 disc areas of retina without atrophy or pigmentary degeneration within the posterior pole; or 3) remaining visual field within 50 degrees of fixation.
  • Willingness to adhere to protocol and long-term follow-up as evidenced by written informed consent or parental permission and subject assent (where applicable).

Exclusion Criteria:

  • Unable or unwilling to meet requirements of the study.
  • Participation in any other study of an investigational drug within the past six months.
  • Use of retinoid compounds or precursors that could potentially interact with the biochemical activity of the RPE65 enzyme; individuals who discontinue use of these compounds for 18 months may become eligible.
  • Prior intraocular surgery within six months.
  • Known sensitivity to medications planned for use in the peri-operative period.
  • Pre-existing eye conditions, such as glaucoma, or complicating systemic diseases that would preclude the planned surgery or could interfere with the interpretation of study. Complicating systemic diseases would include those in which the disease itself, or the treatment for the disease, can alter ocular function. Examples are malignancies whose treatment could affect central nervous system function (for example: radiation treatment of the orbit; leukemia with CNS/optic nerve involvement). Subjects with diabetes or sickle cell disease would be excluded if they had any manifestation of advanced retinopathy (e.g. macular edema or proliferative changes). Also excluded would be subjects with immunodeficiency (acquired or congenital) as there could be susceptibility to opportunistic infection (such as CMV retinitis).
  • Individuals of childbearing potential who are pregnant or unwilling to use effective contraception for four months following vector administration.
  • Any other condition that would not allow the potential subject to complete follow-up examinations during the course of the study and, in the opinion of the investigator, makes the potential subject unsuitable for the study.
  • Subjects will NOT be excluded based on their gender, race, or ethnicity.

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: voretigene neparvovec-rzyl (AAV2-hRPE65v2)
Administration of study agent (AAV2-hRPE65v2) to the previously, uninjected contralateral eye:
Biological: voretigene neparvovec-rzyl
One time, subretinal administration of 1.5E11 vg AAV2-hRPE65v2 vector in 300 microliters to the contralateral, previously uninjected eye.
Other Names:
  • AAV2-hRPE65v2

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse events as a measure of safety and tolerability
Time Frame: 15 years
The primary outcome measures are safety and tolerability. Secondary outcome measure(s) include changes in visual function as measured by subjective, psychophysical tests and by objective, physiologic tests.
15 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Visual acuity
Time Frame: 15 years
The primary outcome measures are safety and tolerability. Secondary outcome measure(s) include changes in visual function as measured by subjective, psychophysical tests and by objective, physiologic tests.
15 years
Visual field
Time Frame: 15 years
The primary outcome measures are safety and tolerability. Secondary outcome measure(s) include changes in visual function as measured by subjective, psychophysical tests and by objective, physiologic tests.
15 years
Pupillary light response
Time Frame: 15 years
The primary outcome measures are safety and tolerability. Secondary outcome measure(s) include changes in visual function as measured by subjective, psychophysical tests and by objective, physiologic tests.
15 years
Mobility testing
Time Frame: 15 years
The primary outcome measures are safety and tolerability. Secondary outcome measure(s) include changes in visual function as measured by subjective, psychophysical tests and by objective, physiologic tests.
15 years
Full-field light threshold sensitivity testing
Time Frame: 15 years
The primary outcome measures are safety and tolerability. Secondary outcome measure(s) include changes in visual function as measured by subjective, psychophysical tests and by objective, physiologic tests.
15 years
Contrast sensitivity
Time Frame: 15 years
The primary outcome measures are safety and tolerability. Secondary outcome measure(s) include changes in visual function as measured by subjective, psychophysical tests and by objective, physiologic tests.
15 years

Collaborators and Investigators

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

Sponsor

Spark Therapeutics

Investigators

  • Study Director: Clinical Director, Spark Therapeutics

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 (Actual)

November 1, 2010

Primary Completion (Estimated)

March 1, 2030

Study Completion (Estimated)

June 1, 2030

Study Registration Dates

First Submitted

September 22, 2010

First Submitted That Met QC Criteria

September 22, 2010

First Posted (Estimated)

September 24, 2010

Study Record Updates

Last Update Posted (Actual)

September 26, 2023

Last Update Submitted That Met QC Criteria

September 25, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AAV2-hRPE65v2-102
  • 10-007752 (Other Identifier: Children's Hospital of Philadelphia)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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.

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