Gene Therapy for Blindness Caused by Choroideremia

Phase 1

Completed

• Conditions: Choroideremia
• Interventions: Drug: rAAV2.REP1

• Registration Number: NCT01461213
• Lead Sponsor: University of Oxford

Brief Summary

- 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

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

Study Timeline

• Study Start: 2011-10
• Study First Submitted: 2011-10-21
• Study First Submitted QC: 2011-10-27
• Study First Posted: 2011-10-28
• Primary Completion: 2017-10
• Study Completion: 2017-10
• Status Verified: 2017-11
• Last Update Submitted: 2017-11-16
• Last Update Posted: 2017-11-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 14

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Dose 1	rAAV2.REP1	Dose 1 = single subretinal injection of vector suspension containing approximately 10e10 rAAV2.REP1 genome particles. Six patients have now received Dose 1.
Dose 2	rAAV2.REP1	Dose 2 = single subretinal injection of vector suspension containing approximately 10e11 rAAV2.REP1 genome particles. Three patients thus far have received Dose 2.

Primary Outcome Measures

Name	Time	Method
Visual acuity	6 months	Best corrected visual acuity, following cataract surgery if indicated

Secondary Outcome Measures

Name	Time	Method
Microperimetry, OCT and fundus autofluorescence	24 months	Structure function correlations at the margins of the retinal degeneration

Trial Locations

Locations (4)

St Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust; 🇬🇧 Manchester, United Kingdom

Oxford Radcliffe Hospitals NHS Trust; 🇬🇧 Oxford, United Kingdom

Eye Unit, Southampton University Hospitals NHS Trust; 🇬🇧 Southampton, United Kingdom

Moorfields Eye Hospital NHS Foundation Trust; 🇬🇧 London, United Kingdom