Safety and Efficacy of rAAV-hRS1 in Patients With X-linked Retinoschisis (XLRS)

June 8, 2023 updated by: Applied Genetic Technologies Corp

A Multiple-Site, Phase 1/2, Safety and Efficacy Trial of a Recombinant Adeno-associated Virus Vector Expressing Retinoschisin (rAAV2tYF-CB-hRS1) in Patients With X-linked Retinoschisis

This study will evaluate the safety and efficacy of a recombinant adeno-associated virus vector expressing retinoschisin (rAAV2tYF-CB-hRS1) in patients with X-linked retinoschisis. Up to 27 participants will be enrolled and 3 dose levels will be evaluated in a dose escalation format.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This will be a non-randomized, open label, Phase 1/2 dose escalation study.

Up to 27 participants will be enrolled. Each participant will receive the study agent by intravitreal injection in one eye on a single occasion. Enrollment will begin with the lowest dose and will proceed to higher doses only after review of safety data by a Data and Safety Monitoring Committee (DSMC). Participants in the dose escalation phase will be ≥ 18 years of age. After the maximum tolerated dose is identified individuals ≥ 6 years of age will be enrolled.

Safety will be measured by the number and proportion of participants experiencing adverse events and immune response to RS1. Efficacy will be measured by evaluation of changes in visual function and schisis cavity size.

Study Type

Interventional

Enrollment (Actual)

27

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
    • California
      • San Francisco, California, United States, 94143
        • University of California San Francisco, Dept. of Ophthalmology
    • Florida
      • Miami, Florida, United States, 33136
        • University of Miami - Miller School of Medicine Bascom Palmer Eye Institute
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • The Wilmer Eye Institute, Johns Hopkins Hospital
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts Eye and Ear Infirmary
    • Michigan
      • Ann Arbor, Michigan, United States, 48105
        • University of Michigan Kellogg Eye Center
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke Eye Center, Duke University Medical Center
    • Oregon
      • Portland, Oregon, United States, 97239
        • Casey Eye Institute, Oregon Health and Sciences University
    • Texas
      • Dallas, Texas, United States, 75231
        • Retina Foundation of the Southwest
      • Houston, Texas, United States, 77030
        • Baylor College of Medicine, Alkek Eye Center

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

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

Accepts Healthy Volunteers

No

Description

Inclusion Criteria include:

  1. Retinal disease consistent with a diagnosis of XLRS and documented mutations in the RS1 gene
  2. Male individual at least 18 years of age (dose escalation phase) or at least 6 years of age (maximum tolerated dose phase),
  3. Able to perform tests of visual and retinal function,
  4. Visual acuity specified for each group
  5. Not treated with CAIs currently or within 3 months prior to study enrollment,
  6. Have acceptable laboratory parameters.

Exclusion Criteria include:

  1. Prior receipt of any AAV gene therapy product,
  2. Pre-existing eye conditions that would preclude the planned intravitreal injection or interfere with interpretation of study endpoints or complications of vector administration.

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: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Groups 1A and 1B
Subjects at least 18 y/o treated with a lower dose of rAAV2tYF-CB-hRS1 study drug.
Biological: rAAV2tYF-CB-hRS1
adeno-associated virus vector expressing retinoschisin
Experimental: Groups 2 and 2A
Subjects at least 6 y/o treated with a middle dose of rAAV2tYF-CB-hRS1 study drug.
Biological: rAAV2tYF-CB-hRS1
adeno-associated virus vector expressing retinoschisin
Experimental: Group 3
Subjects at least 18 y/o treated with a higher dose of rAAV2tYF-CB-hRS1 study drug.
Biological: rAAV2tYF-CB-hRS1
adeno-associated virus vector expressing retinoschisin
Experimental: Group 4
Subjects at least 6 y/o treated with a maximum tolerated dose of rAAV2tYF-CB-hRS1 study drug determined for Groups 1A, 1B, 2 and 3.
Biological: rAAV2tYF-CB-hRS1
adeno-associated virus vector expressing retinoschisin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Experiencing Adverse Events
Time Frame: From Day 0 to Month 12 (12 months)
Number of participants with ocular adverse events, assessed by standard ophthalmic examination, including slit lamp biomicroscopy, tonometry, and indirect ophthalmoscopy.
From Day 0 to Month 12 (12 months)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Best Corrected Visual Acuity (BCVA)
Time Frame: From Day 0 to Month 12 (12 Months)
Change in ETDRS (Early Treatment of Diabetic Retinopathy) Letter Score. Minimum value=0; Maximum value=100. Higher scores indicate better visual acuity. Change = 12 Mo value - Baseline value
From Day 0 to Month 12 (12 Months)
Change From Baseline in Schisis Cavity Size on Optical Coherence Tomography (OCT)
Time Frame: From Day 0 to Month 12 (12 months)
Change in cystic cavity volume (mm^3), obtained from spectral domain optical coherence tomography (SD-OCT) of the retina, yielding volumetric measures of schisis cavity size and total cyst cavity. Change = 12 Mo value - Baseline value
From Day 0 to Month 12 (12 months)
Change From Baseline in B-wave Amplitude in Electroretinogram (ERG) Responses
Time Frame: From Day 0 to Month 12 (12 months)
Change in dark-adapted 3.0 B-wave amplitude (μV). Change = 12 Mo value - Baseline value
From Day 0 to Month 12 (12 months)

Collaborators and Investigators

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

Sponsor

Applied Genetic Technologies Corp

Investigators

  • Study Director: Theresa Heah, MD, Applied Genetics Technologies Corporation

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

Helpful Links

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)

May 1, 2015

Primary Completion (Actual)

April 1, 2019

Study Completion (Actual)

May 9, 2023

Study Registration Dates

First Submitted

April 2, 2015

First Submitted That Met QC Criteria

April 10, 2015

First Posted (Estimated)

April 15, 2015

Study Record Updates

Last Update Posted (Actual)

June 12, 2023

Last Update Submitted That Met QC Criteria

June 8, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AGTC-RS1-001

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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