Back to resultsAn Open Label Clinical Trial of Retinal Gene Therapy for Choroideremia
Primary Purpose
Choroideremia
Status
Completed
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
rAAV2.REP1 vector
Sponsored by
About this trial
This is an interventional treatment trial for Choroideremia focused on measuring choroideremia, gene therapy, gene transfer
Eligibility 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.
Sites / Locations
- University of Alberta
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Open Label
Arm Description
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: http://clinicaltrials.gov/ct2/show/NCT01461213.
Outcomes
Primary Outcome Measures
Number of patients with ocular and systemic adverse events
This is assessed by standard ocular examinations and vector dissemination and inflammation assays.
Secondary Outcome Measures
Changes in visual field
This is assessed by Goldmann perimetry and microperimetry; measurements before and after vector delivery are compared.
Changes in visual function
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.
Full Information
NCT ID
NCT02077361
First Posted
February 26, 2014
Last Updated
May 16, 2022
Sponsor
University of Alberta
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
1. Study Identification
Unique Protocol Identification Number
NCT02077361
Brief Title
An Open Label Clinical Trial of Retinal Gene Therapy for Choroideremia
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)
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
April 2015 (undefined)
Primary Completion Date
August 30, 2017 (Actual)
Study Completion Date
May 16, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Alberta
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
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Choroideremia
Keywords
choroideremia, gene therapy, gene transfer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Open Label
Arm Type
Experimental
Arm Description
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: http://clinicaltrials.gov/ct2/show/NCT01461213.
Intervention Type
Genetic
Intervention Name(s)
rAAV2.REP1 vector
Intervention Description
No additional details needed.
Primary Outcome Measure Information:
Title
Number of patients with ocular and systemic adverse events
Description
This is assessed by standard ocular examinations and vector dissemination and inflammation assays.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Changes in visual field
Description
This is assessed by Goldmann perimetry and microperimetry; measurements before and after vector delivery are compared.
Time Frame
Baseline and up to 2 years following vector delivery
Title
Changes in visual function
Description
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.
Time Frame
Baseline and 2 years following vector delivery
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ian M MacDonald, MD, CM
Organizational Affiliation
University of Alberta
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alberta
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2E1
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
18441370
Citation
Maguire AM, Simonelli F, Pierce EA, Pugh EN Jr, Mingozzi F, Bennicelli J, Banfi S, Marshall KA, Testa F, Surace EM, Rossi S, Lyubarsky A, Arruda VR, Konkle B, Stone E, Sun J, Jacobs J, Dell'Osso L, Hertle R, Ma JX, Redmond TM, Zhu X, Hauck B, Zelenaia O, Shindler KS, Maguire MG, Wright JF, Volpe NJ, McDonnell JW, Auricchio A, High KA, Bennett J. Safety and efficacy of gene transfer for Leber's congenital amaurosis. N Engl J Med. 2008 May 22;358(21):2240-8. doi: 10.1056/NEJMoa0802315. Epub 2008 Apr 27.
Results Reference
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PubMed Identifier
18774912
Citation
Hauswirth WW, Aleman TS, Kaushal S, Cideciyan AV, Schwartz SB, Wang L, Conlon TJ, Boye SL, Flotte TR, Byrne BJ, Jacobson SG. Treatment of leber congenital amaurosis due to RPE65 mutations by ocular subretinal injection of adeno-associated virus gene vector: short-term results of a phase I trial. Hum Gene Ther. 2008 Oct;19(10):979-90. doi: 10.1089/hum.2008.107.
Results Reference
background
PubMed Identifier
18441371
Citation
Bainbridge JW, Smith AJ, Barker SS, Robbie S, Henderson R, Balaggan K, Viswanathan A, Holder GE, Stockman A, Tyler N, Petersen-Jones S, Bhattacharya SS, Thrasher AJ, Fitzke FW, Carter BJ, Rubin GS, Moore AT, Ali RR. Effect of gene therapy on visual function in Leber's congenital amaurosis. N Engl J Med. 2008 May 22;358(21):2231-9. doi: 10.1056/NEJMoa0802268. Epub 2008 Apr 27.
Results Reference
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PubMed Identifier
18209734
Citation
Bennicelli J, Wright JF, Komaromy A, Jacobs JB, Hauck B, Zelenaia O, Mingozzi F, Hui D, Chung D, Rex TS, Wei Z, Qu G, Zhou S, Zeiss C, Arruda VR, Acland GM, Dell'Osso LF, High KA, Maguire AM, Bennett J. Reversal of blindness in animal models of leber congenital amaurosis using optimized AAV2-mediated gene transfer. Mol Ther. 2008 Mar;16(3):458-65. doi: 10.1038/sj.mt.6300389. Epub 2008 Jan 22.
Results Reference
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PubMed Identifier
19806502
Citation
MacLaren RE. An analysis of retinal gene therapy clinical trials. Curr Opin Mol Ther. 2009 Oct;11(5):540-6.
Results Reference
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PubMed Identifier
24439297
Citation
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.
Results Reference
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PubMed Identifier
31269854
Citation
Brooks SP, Benjaminy S, Bubela T. Participant perspectives on a phase I/II ocular gene therapy trial (NCT02077361). Ophthalmic Genet. 2019 Jun;40(3):276-281. doi: 10.1080/13816810.2019.1630843. Epub 2019 Jul 4.
Results Reference
derived
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An Open Label Clinical Trial of Retinal Gene Therapy for Choroideremia
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