Clinical trial NCT02416622: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: X-linked Retinoschisis
Keywords: XLRS
maculoschisis
retinal degeneration
RS1
adeno-associated virus
gene therapy
AAV
Lead sponsor: Beacon Therapeutics
Sponsor class: INDUSTRY
First posted: 2015-04-15
Enrollment: 27
Sex: MALE
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Number of Participants Experiencing Adverse Events
timeFrame: From Day 0 to Month 12 (12 months)
Secondary outcomes:
measure: Change From Baseline in Best Corrected Visual Acuity (BCVA)
timeFrame: From Day 0 to Month 12 (12 Months)
measure: Change From Baseline in Schisis Cavity Size on Optical Coherence Tomography (OCT)
timeFrame: From Day 0 to Month 12 (12 months)
measure: Change From Baseline in B-wave Amplitude in Electroretinogram (ERG) Responses
timeFrame: From Day 0 to Month 12 (12 months)
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco, Dept. of Ophthalmology
state: California
city: Miami
country: United States
facility: University of Miami - Miller School of Medicine Bascom Palmer Eye Institute
state: Florida
city: Baltimore
country: United States
facility: The Wilmer Eye Institute, Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Massachusetts Eye and Ear Infirmary
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Kellogg Eye Center
state: Michigan
city: Durham
country: United States
facility: Duke Eye Center, Duke University Medical Center
state: North Carolina
city: Portland
country: United States
facility: Casey Eye Institute, Oregon Health and Sciences University
state: Oregon
city: Dallas
country: United States
facility: Retina Foundation of the Southwest
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine, Alkek Eye Center
state: Texas
Study officials:
affiliation: Applied Genetics Technologies Corporation
name: Theresa Heah, MD
role: STUDY_DIRECTOR
References:
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.