An Open Label Clinical Trial of Retinal Gene Therapy for Choroideremia

NCT02077361 | Completed Phase 1 DMC

• 2 other identifiers: Pro00028599File # 9427-U0180-84C
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Choroideremia

Keywords

choroideremia; gene therapy; gene transfer

Outcome Measures

Primary Outcomes (1)

• Number of patients with ocular and systemic adverse events

  This is assessed by standard ocular examinations and vector dissemination and inflammation assays.

  2 years

Secondary Outcomes (2)

• Changes in visual field

  Baseline and up to 2 years following vector delivery

• Changes in visual function

  Baseline and 2 years following vector delivery

Study Arms (1)

Open Label

EXPERIMENTAL

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.

Genetic: rAAV2.REP1 vector

Interventions

rAAV2.REP1 vector GENETIC

No additional details needed.

Open Label

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Alberta: lead
• Alberta Innovates Health Solutions: collaborator
• Canada Foundation for Innovation: collaborator
• Canadian Institutes of Health Research (CIHR): collaborator
• Choroideremia Research Foundation Canada: collaborator
• Foundation Fighting Blindness: collaborator
• Imperial College London: collaborator
• University of Oxford: collaborator

Study Sites (1)

University of Alberta

Edmonton, Alberta, T6G 2E1, Canada

Location

Related Publications (7)

• 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.

  PMID: 18441370 BACKGROUND

• 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.

  PMID: 18774912 BACKGROUND

• 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.

  PMID: 18441371 BACKGROUND

• 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.

  PMID: 18209734 BACKGROUND

• MacLaren RE. An analysis of retinal gene therapy clinical trials. Curr Opin Mol Ther. 2009 Oct;11(5):540-6.

  PMID: 19806502 BACKGROUND

• 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.

  PMID: 24439297 BACKGROUND

• 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.

  PMID: 31269854 DERIVED

Related Links

• Choroideremia Overview

MeSH Terms

Conditions

Choroideremia

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Choroid Diseases; Uveal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked

Study Officials

• Ian M MacDonald, MD, CM

  University of Alberta

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2014
• First Posted: March 4, 2014
• Study Start: April 1, 2015
• Primary Completion: August 30, 2017
• Study Completion: May 16, 2022
• Last Updated: May 19, 2022

Record last verified: 2022-05

Locations

CA (1)