Clinical Evaluation of Patients With X-linked Retinoschisis

• ClinicalTrials.gov Identifier: NCT02331173
• Recruitment Status: Completed
• First Posted: January 6, 2015
• Last Update Posted: November 17, 2017
• Sponsor: Applied Genetic Technologies Corp
• Collaborator: Foundation Fighting Blindness
• Information provided by (Responsible Party): Applied Genetic Technologies Corp

Study Description

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.

Condition or disease	Intervention/treatment
X-linked Retinoschisis; XLRS	Drug: Dorzolamide 2% TID or brinzolamide 1% TID

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 Design

• Study Type: Observational
• Actual Enrollment: 66 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Clinical Evaluation of Patients With X-linked Retinoschisis (XLRS)
• Study Start Date: November 2012
• Actual Primary Completion Date: October 2016
• Actual Study Completion Date: October 2016

Groups and Cohorts

Group/Cohort	Intervention/treatment
Main Study Group; All subjects enrolled in this study will be seen every 6 months following the screening visit. During the 3 main study visits, a series of tests will be performed to assess visual function. Some of these tests are part of routine care that patients would receive on an annual basis regardless of study participation. Other tests are being performed to determine if they are effective at monitoring disease progression in this population. For each of the 3 main study visits, testing may be spread over multiple days to ensure completion of all tests.
Carbonic anhydrase inhibitor sub-study; 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).	Drug: Dorzolamide 2% TID or brinzolamide 1% TID; Dosing of all medications will be based upon standard of care. Standard dosing for the treatment of pediatric and adult patients with XLRS is as follows: Topical dorzolamide 2% three times per day; Topical brinzolamide 1% three times per day

Outcome Measures

Primary Outcome Measures :

1. Disease progression in subjects with XLRS [ Time Frame: Every 6 months for 18 months ]

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 7 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No
• Sampling Method: Probability Sample

Study Population

Potential subjects will be identified from the Oregon Retinal Degeneration Center (ORDC) database and the Retina and Ophthalmic practices at Oregon Health and Science University Casey Eye Institute, Retina Foundation of the Southwest and Kellogg Eye Center.

Criteria

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

Contacts and Locations

Locations

United States, Michigan

University of Michigan Kellogg Eye Center

Ann Arbor, Michigan, United States, 48105

United States, Oregon

Casey Eye Institute, Oregon Health and Sciences University

Portland, Oregon, United States, 97239

United States, Texas

Retina Foundation of the Southwest

Dallas, Texas, United States, 75231

Sponsors and Collaborators

Applied Genetic Technologies Corp

Foundation Fighting Blindness

Investigators

• Study Director: Matt Feinsod, MD; Applied Genetics Technologies Corporation

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Pennesi ME, Birch DG, Jayasundera KT, Parker M, Tan O, Gurses-Ozden R, Reichley C, Beasley KN, Yang P, Weleber RG, Bennett LD, Heckenlively JR, Kothapalli K, Chulay JD, For The Xlrs-Study Group. Prospective Evaluation of Patients With X-Linked Retinoschisis During 18 Months. Invest Ophthalmol Vis Sci. 2018 Dec 3;59(15):5941-5956. doi: 10.1167/iovs.18-24565.

• Responsible Party: Applied Genetic Technologies Corp
• ClinicalTrials.gov Identifier: NCT02331173 History of Changes
• Other Study ID Numbers: XLRS-001
• First Posted: January 6, 2015
• Last Update Posted: November 17, 2017
• Last Verified: October 2017

Keywords provided by Applied Genetic Technologies Corp:

XLRS; RS1; maculoschisis

Additional relevant MeSH terms:

Retinoschisis; Retinal Degeneration; Retinal Diseases; Eye Diseases; Dorzolamide; Brinzolamide; Carbonic Anhydrase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents