An Open Label Clinical Trial of Retinal Gene Therapy for Choroideremia


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.

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

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: August 30, 2017

Detailed Description

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.


  • Genetic: rAAV2.REP1 vector
    • No additional details needed.

Arms, Groups and Cohorts

  • Experimental: Open Label
    • 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:

Clinical Trial Outcome Measures

Primary Measures

  • Number of patients with ocular and systemic adverse events
    • Time Frame: 2 years
    • This is assessed by standard ocular examinations and vector dissemination and inflammation assays.

Secondary Measures

  • Changes in visual field
    • Time Frame: Baseline and up to 2 years following vector delivery
    • This is assessed by Goldmann perimetry and microperimetry; measurements before and after vector delivery are compared.
  • Changes in visual function
    • Time Frame: Baseline and 2 years following vector delivery
    • 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.

Participating in This Clinical Trial

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.

Gender Eligibility: Male

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Ian M. MacDonald
  • Collaborator
    • Alberta Innovates Health Solutions
  • Provider of Information About this Clinical Study
    • Sponsor-Investigator: Ian M. MacDonald, Professor, Department of Ophthalmology and Visual Sciences – University of Alberta
  • Overall Official(s)
    • Ian M MacDonald, MD, CM, Principal Investigator, University of Alberta


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MacLaren RE, Groppe M, Barnard AR, Cottriall CL, Tolmachova T, Seymour L, Clark KR, During MJ, Cremers FP, Black GC, Lotery AJ, Downes SM, Webster AR, Seabra MC. Retinal gene therapy in patients with choroideremia: initial findings from a phase 1/2 clinical trial. Lancet. 2014 Mar 29;383(9923):1129-37. doi: 10.1016/S0140-6736(13)62117-0. Epub 2014 Jan 16.

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