Gene Therapy for Blindness Caused by Choroideremia

Study Overview
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Brief Summary
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- Primary objective: To assess the safety and tolerability of the AAV.REP1 vector, administered at two different doses to the retina in 12 patients with a diagnosis of choroideremia. - Secondary Objective: To identify any therapeutic benefit as evidenced by a slowing down of the retinal degeneration assessed by functional and anatomical methods in the treated eye compared to the control eye 24 months after gene delivery.

Detailed Description
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Detailed description may be found in the following scientific publication: Retinal gene therapy in patients with choroideremia: initial findings from a phase 1/2 clinical trial, The Lancet, Volume 383, Issue 9923, Pages 1129 - 1137 (29 March 2014). Links: www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)62117-0/abstract ; http://dx.doi.org/doi:10.1016/S0140-6736(13)62117-0

Official Title
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An Open Label Dose Escalation Phase 1 Clinical Trial of Retinal Gene Therapy for Choroideraemia 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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* Drug: rAAV2.REP1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant is willing and able to give informed consent for participation in the study, Male aged 18 years or above, Diagnosed with choroideraemia and in good health, Active disease with SLO changes visible within the macula region, Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the study, Vision at least 6/60 or better in the study eye. Exclusion Criteria: Female and child participants (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 disease or other ocular morbidity which might confound use of the fellow eye as a long-term control, Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study, Participants who have participated in another research study involving an investigational product in the previous 12 weeks.

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose 1<br>Dose 1 = single subretinal injection of vector suspension containing approximately 10e10 rAAV2.REP1 genome particles. Six patients have now received Dose 1. | Drug: rAAV2.REP1<br>* Single subretinal injection of rAAV2.REP1 vector suspension containing 10e12 genome particles per ml. Dose 1 = dose containing approximately 10e10 rAAV2.REP1 genome particles. Dose 2 = dose containing approximately 10e11 rAAV2.REP1 genome particles.<br>* Other names: Adeno-associated viral vector;|
| Experimental: Dose 2<br>Dose 2 = single subretinal injection of vector suspension containing approximately 10e11 rAAV2.REP1 genome particles. Three patients thus far have received Dose 2. | Drug: rAAV2.REP1<br>* Single subretinal injection of rAAV2.REP1 vector suspension containing 10e12 genome particles per ml. Dose 1 = dose containing approximately 10e10 rAAV2.REP1 genome particles. Dose 2 = dose containing approximately 10e11 rAAV2.REP1 genome particles.<br>* Other names: Adeno-associated viral vector;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual acuity | Best corrected visual acuity, following cataract surgery if indicated | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microperimetry, OCT and fundus autofluorescence | Structure function correlations at the margins of the retinal degeneration | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tapetoretinal degeneration, choroideraemia, X-linked, retinitis pigmentosa