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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02416622
Recruitment Status : Active, not recruiting
First Posted : April 15, 2015
Results First Posted : July 1, 2020
Last Update Posted : July 20, 2022
Sponsor:
Information provided by (Responsible Party):
Applied Genetic Technologies Corp

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
X-linked Retinoschisis Biological: rAAV2tYF-CB-hRS1 Phase 1 Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : May 2015
Actual Primary Completion Date : April 2019
Estimated Study Completion Date : October 2023

Resource links provided by the National Library of Medicine


Arms and Interventions
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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


Outcome Measures
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Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   6 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02416622


Locations
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United States, California
University of California San Francisco, Dept. of Ophthalmology
San Francisco, California, United States, 94143
United States, Florida
University of Miami - Miller School of Medicine Bascom Palmer Eye Institute
Miami, Florida, United States, 33136
United States, Maryland
The Wilmer Eye Institute, Johns Hopkins Hospital
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Massachusetts Eye and Ear Infirmary
Boston, Massachusetts, United States, 02114
United States, Michigan
University of Michigan Kellogg Eye Center
Ann Arbor, Michigan, United States, 48105
United States, North Carolina
Duke Eye Center, Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Oregon
Casey Eye Institute, Oregon Health and Sciences University
Portland, Oregon, United States, 97239
United States, Texas
Retina Foundation of the Southwest
Dallas, Texas, United States, 75231
Baylor College of Medicine, Alkek Eye Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Applied Genetic Technologies Corp
Investigators
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Study Director: Theresa Heah, MD Applied Genetics Technologies Corporation
  Study Documents (Full-Text)

Documents provided by Applied Genetic Technologies Corp:
Study Protocol  [PDF] October 21, 2019
Statistical Analysis Plan  [PDF] August 8, 2017

More Information
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Additional Information:

Publications:

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Responsible Party: Applied Genetic Technologies Corp
ClinicalTrials.gov Identifier: NCT02416622    
Other Study ID Numbers: AGTC-RS1-001
First Posted: April 15, 2015    Key Record Dates
Results First Posted: July 1, 2020
Last Update Posted: July 20, 2022
Last Verified: July 2022
Keywords provided by Applied Genetic Technologies Corp:
XLRS
maculoschisis
retinal degeneration
RS1
 adeno-associated virus
gene therapy
AAV
Additional relevant MeSH terms:
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Retinoschisis
Retinal Degeneration
Retinal Diseases
Eye Diseases