An Open Label Clinical Trial of Retinal Gene Therapy for Choroideremia

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified April 2014 by University of Alberta
Sponsor:
Collaborators:
Alberta Innovates Health Solutions
Canada Foundation for Innovation
Canadian Institutes of Health Research (CIHR)
Choroideremia Research Foundation Canada
Foundation Fighting Blindness
Imperial College London
University of Oxford
Information provided by (Responsible Party):
Ian M. MacDonald, University of Alberta
ClinicalTrials.gov Identifier:
NCT02077361
First received: February 26, 2014
Last updated: April 30, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Choroideremia
Genetic: rAAV2.REP1 vector
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label Clinical Trial of Retinal Gene Therapy for Choroideremia Using an Adeno-associated Viral Vector (AAV2) Encoding Rab-escort Protein-1 (REP1)

Resource links provided by NLM:


Further study details as provided by University of Alberta:

Primary Outcome Measures:
  • Number of patients with ocular and systemic adverse events [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    This is assessed by standard ocular examinations and vector dissemination and inflammation assays.


Secondary Outcome Measures:
  • Changes in visual field [ Time Frame: Baseline and up to 2 years following vector delivery ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 12
Study Start Date: September 2014
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Open Label

Patients will receive a subretinal injection of 0.10 ml of the rAAV2.REP1 vector drug substance (10e11 AAV2 genome particles). 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 trial logged at: http://clinicaltrials.gov/ct2/show/NCT01461213.

Genetic: rAAV2.REP1 vector
No additional details needed.

Detailed Description:

This is an open label study involving a total of 12 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02077361

Contacts
Contact: Stephanie Chan, MSc 7804928869 scchan@ualberta.ca

Locations
Canada, Alberta
University of Alberta Not yet recruiting
Edmonton, Alberta, Canada, T6G 2E1
Principal Investigator: Ian M MacDonald, MD, CM         
Sub-Investigator: Tania Bubela, PhD, LLB         
Sub-Investigator: Elena Posse de Chaves, PhD(Hons)         
Sub-Investigator: Yves Sauve, PhD         
Sub-Investigator: Matthew Tennant, MD, FRCSC         
Sub-Investigator: Riz Somani, MD, FRCSC         
Sub-Investigator: Miguel Seabra, MD, PhD         
Sub-Investigator: Robert MacLaren, DPhil FRCS FRCOphth         
Sponsors and Collaborators
Ian M. MacDonald
Alberta Innovates Health Solutions
Canada Foundation for Innovation
Canadian Institutes of Health Research (CIHR)
Choroideremia Research Foundation Canada
Foundation Fighting Blindness
Imperial College London
University of Oxford
Investigators
Principal Investigator: Ian M MacDonald, MD, CM University of Alberta
  More Information

Additional Information:
Publications:

Responsible Party: Ian M. MacDonald, Professor and Chair, Department of Ophthalmology and Visual Sciences, University of Alberta
ClinicalTrials.gov Identifier: NCT02077361     History of Changes
Other Study ID Numbers: Pro00028599, File # 9427-U0180-84C
Study First Received: February 26, 2014
Last Updated: April 30, 2014
Health Authority: Canada: Health Canada

Keywords provided by University of Alberta:
choroideremia
gene therapy
gene transfer

Additional relevant MeSH terms:
Choroideremia
Eye Diseases, Hereditary
Eye Diseases
Choroid Diseases
Uveal Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked

ClinicalTrials.gov processed this record on July 22, 2014