Clinical Evaluation of Patients With X-linked Retinoschisis

Completed

• Conditions: XLRS; X-linked Retinoschisis
• Interventions: Drug: Dorzolamide 2% TID or brinzolamide 1% TID

• Registration Number: NCT02331173
• Lead Sponsor: Applied Genetic Technologies Corp

Brief Summary

The purpose of this study is to evaluate subjects with X-linked retinoschisis in a clinical setting to collect data on disease progression.

Detailed Description

The objective of the study is to evaluate subjects with XLRS in a clinical setting and gather data on disease progression. The data from this study will enhance the understanding of the natural history of this rare disease and will facilitate appropriately powered safety studies in a future gene therapy trial in humans.

Study Timeline

• Study Start: 2012-11
• Study First Submitted: 2014-12-08
• Study First Submitted QC: 2015-01-02
• Study First Posted: 2015-01-06
• Primary Completion: 2016-10
• Study Completion: 2016-10
• Status Verified: 2017-10
• Last Update Submitted: 2017-11-15
• Last Update Posted: 2017-11-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 66

Inclusion Criteria

Main Study:

• Clinical diagnosis consistent with XLRS
• Documented disease causing RS1 mutation
• 7 years of age or older
• Able to provide informed consent/assent
• Male

CAI sub-study:

• Presence of maculoschisis

Exclusion Criteria

Main Study:

• Other eye diseases that might affect the results (e.g. history of retinal detachment, glaucoma, cataracts that prohibit imaging, or any other eye pathology that in the opinion of the investigator would preclude enrollment)

CAI Sub-study:

Exclusion Criteria

• Already being treated with CAIs
• Previous documented failure to respond to CAI treatment

Any drug-specific contraindication/precaution listed below (from www.micromedex.com):

Topical Eye Drop Dorzolamide Hydrochloride

Contraindications:

• hypersensitivity to dorzolamide products, including sulfa allergies

Precautions:

• dorzolamide is a sulfonamide that is absorbed systemically, sulfonamide hypersensitivity reactions may occur
• angle-closure glaucoma
• concomitant use of oral carbonic-anhydrase inhibitors
• conjunctivitis and lid reactions reported with chronic administration
• moderate to severe renal (CrCl less than 30 mL/min) or hepatic insufficiency
• ocular infection or inflammation
• recent ocular surgery

Topical Eye Drop Brinzolamide

Contraindications:

• hypersensitivity to any component of the product, including sulfa allergies

Precautions:

• concomitant use of oral carbonic anhydrase inhibitors is not recommended
• contact lens use; remove contact lenses prior to administration, allow 15 minutes before reinsertion
• hypersensitivity to sulfonamides; severe reaction may occur; discontinue if signs or symptoms appear
• low corneal endothelial cell counts; increased risk of corneal edema
• renal impairment, severe (CrCl less than 30 mL/min); use not recommended

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Carbonic anhydrase inhibitor sub-study	Dorzolamide 2% TID or brinzolamide 1% TID	Subjects with maculoschisis may be offered topical treatment with CAIs. These subjects will be asked to visit the study site at 1 month and 3 months after starting topical treatment. During these additional visits, subjects will undergo a dilated eye exam, BCVA, and SD-OCT imaging to assess efficacy of treatment (i.e. reduction of maculoschisis).

Primary Outcome Measures

Name	Time	Method
Disease progression in subjects with XLRS	Every 6 months for 18 months

Secondary Outcome Measures

Name	Time	Method
Disease progression using microperimetry, a non-standard of care visual function test	Every 6 months for 18 months
Disease progression using electroretinograms (ERGs), a non-standard of care visual function test	Every 6 months for 18 months
Disease progression using the reading speed test, a non-standard of care visual function test	Every 6 months for 18 months
Disease progression using the contrast sensitivity test, a non-standard of care visual function test	Every 6 months for 18 months
Disease progression using a quality of life questionnaire	Every 6 months for 18 months
Change in maculoschisis while receiving carbonic anhydrase inhibitors	All study visits, Months 1, 3, 6, 12, and 18
Change in visual function while receiving carbonic anhydrase inhibitors	All study visits, Months 1, 3, 6, 12, and 18

Trial Locations

Locations (3)

University of Michigan Kellogg Eye Center; 🇺🇸 Ann Arbor, Michigan, United States

Retina Foundation of the Southwest; 🇺🇸 Dallas, Texas, United States

Casey Eye Institute, Oregon Health and Sciences University; 🇺🇸 Portland, Oregon, United States