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

X-linked Retinoschisis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02416622
• Other study ID #: AGTC-RS1-001
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: May 2015
• Est. completion date: May 9, 2023

Study information

• Verified date: June 2023
• Source: Applied Genetic Technologies Corp
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: May 9, 2023
• Est. primary completion date: April 2019
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 6 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Retinoschisis
• X-linked Retinoschisis

Intervention

Biological:
• rAAV2tYF-CB-hRS1
adeno-associated virus vector expressing retinoschisin

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Applied Genetic Technologies Corp

Country where clinical trial is conducted

United States, 

References & Publications (1)

Molday RS, Kellner U, Weber BH. X-linked juvenile retinoschisis: clinical diagnosis, genetic analysis, and molecular mechanisms. Prog Retin Eye Res. 2012 May;31(3):195-212. doi: 10.1016/j.preteyeres.2011.12.002. Epub 2012 Jan 3. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Experiencing Adverse Events	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	Change From Baseline in Best Corrected Visual Acuity (BCVA)	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)
Secondary	Change From Baseline in Schisis Cavity Size on Optical Coherence Tomography (OCT)	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)
Secondary	Change From Baseline in B-wave Amplitude in Electroretinogram (ERG) Responses	Change in dark-adapted 3.0 B-wave amplitude (µV). Change = 12 Mo value - Baseline value	From Day 0 to Month 12 (12 months)

External Links

•   AGTC website