An Open Label Clinical Trial of Retinal Gene Therapy for Choroideremia

Study Overview
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Brief Summary
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A project has been developed in Edmonton, Alberta, Canada to enable male patients with choroideremia to access a clinical trial that replaces the defective gene with a normal copy. This experiment is designed to show that the transfer of a normal copy of the gene to the eye is not only safe but may improve the sight of patients. Only Canadian subjects who meet criteria will be recruited.

Detailed Description
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This is an open label study involving a total of 6 male patients. Screening and patient medical records will determine patient eligibility. Patients will receive a subretinal injection of the rAAV2.REP1 vector by a trained vitreoretinal surgeon in one eye. Each patient will be followed up for 24 months after treatment to assess the primary and secondary endpoints of this study using a number of outcome measures. However, further follow-up will continue after the study on an annual basis for a minimum of ten years. Data will continue to be analyzed by members of the study group after this study is complete.

Official Title
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An Open Label Clinical Trial of Retinal Gene Therapy for Choroideremia Using an Adeno-associated Viral Vector (AAV2) Encoding Rab-escort Protein-1 (REP1)

Conditions
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Choroideremia

Intervention / Treatment
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* Genetic: rAAV2.REP1 vector


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The research subject is willing and able to give informed consent for participation in the study. Male aged 18 years or above. Diagnosed with choroideremia (with genotyping or evidence of lack of the gene product with immunohistochemistry) and in good health. Active degeneration of the retina (the expectation of significant decline in visual function without any intervention over the subsequent 5 years) with OCT (optical coherent tomography) changes visible within the macula. Willingness to allow his general physician and ophthalmologist, if appropriate, to be notified of participation in the study. Exclusion Criteria: The participant may not enter the study if ANY of the following apply. Female or child research subject (under the age of 18). Men unwilling to use barrier contraception methods, if relevant. Previous history of retinal surgery or ocular inflammatory disease (uveitis). Grossly asymmetrical retinal disease or other ocular morbidity which might confound adopting the fellow eye as a long-term comparator. Any other significant systemic disease or disorder which, in the opinion of the investigator, may either put the research subject at risk because of participation in the study, or may influence the result of the study, or the research subject's ability to participate in the study. This would include a contraindication to oral prednisolone, such as a history of gastric ulcer). Research subjects who have participated in another research study involving an investigational product within the past year.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open Label<br>Patients will receive a subretinal injection of 0.10 ml of the rAAV2.REP1 vector drug substance. It is a colourless opalescent frozen liquid with no visible particles. Each patient will be given a one-time dose in one eye. It is the same vector used in the United Kingdom Phase I/II trial logged at: http://clinicaltrials.gov/ct2/show/NCT01461213. | Genetic: rAAV2.REP1 vector<br>* No additional details needed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with ocular and systemic adverse events | This is assessed by standard ocular examinations and vector dissemination and inflammation assays. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in visual field | This is assessed by Goldmann perimetry and microperimetry; measurements before and after vector delivery are compared. | Baseline and up to 2 years following vector delivery | 
| Changes in visual function | This is assessed by multifocal electrophysiology, full field scotopic threshold, spectral domain optical coherent tomography, fundus photography and fundus autofluorescence; measurements before and after vector delivery are compared. | Baseline and 2 years following vector delivery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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choroideremia, gene therapy, gene transfer