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

Applied Genetic Technologies (AGTC)

Status and phase: Completed; Phase 2; Phase 1

Conditions: X-linked Retinoschisis

Treatments: Biological: rAAV2tYF-CB-hRS1

Study type: Interventional

Funder types: Other

Identifiers

NCT02416622

AGTC-RS1-001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 27 patients

Sex: Male

Ages: 6+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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27 participants in 4 patient groups

Groups 1A and 1B

Experimental group

Description:

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

Treatment:

Biological: rAAV2tYF-CB-hRS1

Groups 2 and 2A

Experimental group

Description:

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

Treatment:

Biological: rAAV2tYF-CB-hRS1

Group 3

Experimental group

Description:

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

Treatment:

Biological: rAAV2tYF-CB-hRS1

Group 4

Experimental group

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.

Treatment:

Biological: rAAV2tYF-CB-hRS1