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

Phase 1

Completed

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.

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.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
Groups 1A and 1B	rAAV2tYF-CB-hRS1	Subjects at least 18 y/o treated with a lower dose of rAAV2tYF-CB-hRS1 study drug.
Groups 2 and 2A	rAAV2tYF-CB-hRS1	Subjects at least 6 y/o treated with a middle dose of rAAV2tYF-CB-hRS1 study drug.
Group 3	rAAV2tYF-CB-hRS1	Subjects at least 18 y/o treated with a higher dose of rAAV2tYF-CB-hRS1 study drug.
Group 4	rAAV2tYF-CB-hRS1	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants Experiencing Adverse Events	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

Name	Time	Method
Change From Baseline in Schisis Cavity Size on Optical Coherence Tomography (OCT)	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
Change From Baseline in B-wave Amplitude in Electroretinogram (ERG) Responses	From Day 0 to Month 12 (12 months)	Change in dark-adapted 3.0 B-wave amplitude (μV). Change = 12 Mo value - Baseline value
Change From Baseline in Best Corrected Visual Acuity (BCVA)	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

Locations (9): University of Michigan Kellogg Eye Center
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Ann Arbor, Michigan, United States
Retina Foundation of the Southwest
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Dallas, Texas, United States
Casey Eye Institute, Oregon Health and Sciences University
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Portland, Oregon, United States
The Wilmer Eye Institute, Johns Hopkins Hospital
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Baltimore, Maryland, United States
University of Miami - Miller School of Medicine Bascom Palmer Eye Institute
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Miami, Florida, United States
Massachusetts Eye and Ear Infirmary
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Boston, Massachusetts, United States
Baylor College of Medicine, Alkek Eye Center
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Houston, Texas, United States
University of California San Francisco, Dept. of Ophthalmology
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San Francisco, California, United States
Duke Eye Center, Duke University Medical Center
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Durham, North Carolina, United States