Clinical Evaluation of Patients With X-linked Retinoschisis

Sponsor

Applied Genetic Technologies Corp (Industry)

Overall Status

Completed

CT.gov ID

NCT02331173

Collaborator

Foundation Fighting Blindness (Other)

Enrollment

Locations

Duration (Months)

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

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	Phase
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 :

Nov 1, 2012

Actual Primary Completion Date :

Oct 1, 2016

Actual Study Completion Date :

Oct 1, 2016

Arms and Interventions

Arm	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

Arm

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

Disease progression in subjects with XLRS [Every 6 months for 18 months]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

7 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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

	Site	City	State	Country	Postal Code
1	University of Michigan Kellogg Eye Center	Ann Arbor	Michigan	United States	48105
2	Casey Eye Institute, Oregon Health and Sciences University	Portland	Oregon	United States	97239
3	Retina Foundation of the Southwest	Dallas	Texas	United States	75231