REP1 Gene Replacement Therapy for Choroideremia

Study Overview
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Brief Summary
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The assessment of the efficacy (with respect to preservation of visual function and retinal structure) and safety of a single subretinal injection of AAV2.REP1 in participants with a confirmed diagnosis of choroideremia, as evaluated by various functional and anatomical outcomes measured over a number of time points up to 24 months post-treatment.

Official Title
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An Open Label Phase 2 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: AAV-mediated REP1 gene replacement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Candidate is willing and able to give informed consent for participation in the study. Male aged 18 years or above. Genetic or molecular confirmed diagnosis of choroideremia (REP1 protein deficiency). Active disease visible clinically within the macula region. Best corrected visual acuity better than or equal to 6/60 (20/200; Decimal 0.1; LogMAR 1.0) in the study eye. Exclusion Criteria: Any female, or a male aged below 18 years. An additional cause for sight loss (e.g. amblyopia) in the eye to be treated. Any other significant ocular and non-ocular disease or disorder which, in the opinion of the investigator, may put the participants at risk because of participation in the study. Inability to take systemic prednisolone for a period of 45 days. Unwillingness to use barrier contraception methods for a period of three months following gene therapy surgery. Participation in another research study involving an investigational product in the preceding 12 weeks.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The decision about which eye to treat will be made on clinical grounds and will generally be the worse eye affected in cases where BCVA differs between the two eyes by 2 lines or more of ETDRS letters. The eye to be treated will be randomised in cases where the degeneration is relatively symmetrical between the two eyes, defined as: a difference in BCVA of no more than 1 line of ETDRS letters, and no more than 25% difference in the area of surviving RPE as measured by fundus autofluorescence. Prospective participants having non-symmetrical retinal degeneration will be allocated to the non-randomised arm. The treated eye will generally be the worse eye. Prospective participants having relatively symmetrical retinal degeneration will be allocated to the randomised arm.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>Treated eye undergoes AAV-mediated REP1 gene replacement. AAV vector is delivered by subretinal injection. | Genetic: AAV-mediated REP1 gene replacement<br>* AAV vector carrying human REP1 gene is delivered into the treated eye by subretinal injection<br>|
| No Intervention: Control<br>Untreated eye | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in best corrected visual acuity in the treated eye |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in the central visual field in the treated eye as determined by microperimetry |  | 2 years | 
| Change from baseline in the area of surviving retinal pigment epithelium in the treated eye as measured by fundus autofluorescence, compared to the untreated fellow eye (control eye) after randomisation of treatment to one eye or the other |  | 2 years |