Back to results

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

Primary Purpose

X-linked Retinoschisis

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

rAAV2tYF-CB-hRS1

About this trial

This is an interventional treatment trial for X-linked Retinoschisis focused on measuring XLRS, maculoschisis, retinal degeneration, RS1, adeno-associated virus, gene therapy, AAV

Eligibility Criteria

6 Years - undefined (Child, Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria include:

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

Exclusion Criteria include:

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

Sites / Locations

University of California San Francisco, Dept. of Ophthalmology
University of Miami - Miller School of Medicine Bascom Palmer Eye Institute
The Wilmer Eye Institute, Johns Hopkins Hospital
Massachusetts Eye and Ear Infirmary
University of Michigan Kellogg Eye Center
Duke Eye Center, Duke University Medical Center
Casey Eye Institute, Oregon Health and Sciences University
Retina Foundation of the Southwest
Baylor College of Medicine, Alkek Eye Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Groups 1A and 1B

Groups 2 and 2A

Group 3

Group 4

Arm Description

Subjects at least 18 y/o treated with a lower dose of rAAV2tYF-CB-hRS1 study drug.

Subjects at least 6 y/o treated with a middle dose of rAAV2tYF-CB-hRS1 study drug.

Subjects at least 18 y/o treated with a higher dose of rAAV2tYF-CB-hRS1 study drug.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

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

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

Full Information

NCT ID

NCT02416622

First Posted

April 2, 2015

Last Updated

June 8, 2023

Sponsor

Applied Genetic Technologies Corp

1. Study Identification

Unique Protocol Identification Number

NCT02416622

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Completed

Study Start Date

May 2015 (Actual)

Primary Completion Date

April 2019 (Actual)

Study Completion Date

May 9, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Applied Genetic Technologies Corp

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

X-linked Retinoschisis

Keywords

XLRS, maculoschisis, retinal degeneration, RS1, adeno-associated virus, gene therapy, AAV

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

27 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Groups 1A and 1B

Arm Type

Experimental

Arm Description

Subjects at least 18 y/o treated with a lower dose of rAAV2tYF-CB-hRS1 study drug.

Arm Title

Groups 2 and 2A

Arm Type

Experimental

Arm Description

Subjects at least 6 y/o treated with a middle dose of rAAV2tYF-CB-hRS1 study drug.

Arm Title

Group 3

Arm Type

Experimental

Arm Description

Subjects at least 18 y/o treated with a higher dose of rAAV2tYF-CB-hRS1 study drug.

Arm Title

Group 4

Arm Type

Experimental

Arm Description

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.

Intervention Type

Biological

Intervention Name(s)

rAAV2tYF-CB-hRS1

Intervention Description

adeno-associated virus vector expressing retinoschisin

Primary Outcome Measure Information:

Title

Number of Participants Experiencing Adverse Events

Description

Number of participants with ocular adverse events, assessed by standard ophthalmic examination, including slit lamp biomicroscopy, tonometry, and indirect ophthalmoscopy.

Time Frame

From Day 0 to Month 12 (12 months)

Secondary Outcome Measure Information:

Title

Change From Baseline in Best Corrected Visual Acuity (BCVA)

Description

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

Time Frame

From Day 0 to Month 12 (12 Months)

Title

Change From Baseline in Schisis Cavity Size on Optical Coherence Tomography (OCT)

Description

Time Frame

From Day 0 to Month 12 (12 months)

Title

Change From Baseline in B-wave Amplitude in Electroretinogram (ERG) Responses

Description

Change in dark-adapted 3.0 B-wave amplitude (μV). Change = 12 Mo value - Baseline value

Time Frame

From Day 0 to Month 12 (12 months)

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

6 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria include: Retinal disease consistent with a diagnosis of XLRS and documented mutations in the RS1 gene Male individual at least 18 years of age (dose escalation phase) or at least 6 years of age (maximum tolerated dose phase), Able to perform tests of visual and retinal function, Visual acuity specified for each group Not treated with CAIs currently or within 3 months prior to study enrollment, Have acceptable laboratory parameters. Exclusion Criteria include: Prior receipt of any AAV gene therapy product, Pre-existing eye conditions that would preclude the planned intravitreal injection or interfere with interpretation of study endpoints or complications of vector administration.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Theresa Heah, MD

Organizational Affiliation

Applied Genetics Technologies Corporation

Official's Role

Study Director

Facility Information:

Facility Name

University of California San Francisco, Dept. of Ophthalmology

City

San Francisco

State/Province

California

ZIP/Postal Code

94143

Country

United States

Facility Name

University of Miami - Miller School of Medicine Bascom Palmer Eye Institute

City

Miami

State/Province

Florida

ZIP/Postal Code

33136

Country

United States

Facility Name

The Wilmer Eye Institute, Johns Hopkins Hospital

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21287

Country

United States

Facility Name

Massachusetts Eye and Ear Infirmary

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

Facility Name

University of Michigan Kellogg Eye Center

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48105

Country

United States

Facility Name

Duke Eye Center, Duke University Medical Center

City

Durham

State/Province

North Carolina

ZIP/Postal Code

27710

Country

United States

Facility Name

Casey Eye Institute, Oregon Health and Sciences University

City

Portland

State/Province

Oregon

ZIP/Postal Code

97239

Country

United States

Facility Name

Retina Foundation of the Southwest

City

Dallas

State/Province

Texas

ZIP/Postal Code

75231

Country

United States

Facility Name

Baylor College of Medicine, Alkek Eye Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

22245536

Citation

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.

Results Reference

background

Links:

URL

http://agtc.com

Description

AGTC website

Learn more about this trial

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

We'll reach out to this number within 24 hrs