An Open Label Clinical Trial of Retinal Gene Therapy for Choroideremia

Choroideremia Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02077361
• Other study ID #: Pro00028599
• Secondary ID: File # 9427-U018
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: April 2015
• Est. completion date: May 16, 2022

Study information

• Verified date: May 2022
• Source: University of Alberta
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: May 16, 2022
• Est. primary completion date: August 30, 2017
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Choroideremia

Intervention

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

Locations

Country	Name	City	State
Canada	University of Alberta	Edmonton	Alberta

Sponsors (8)

Lead Sponsor	Collaborator
University of Alberta	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

Country where clinical trial is conducted

Canada, 

References & Publications (6)

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. — View 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. — View 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. — View 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. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Changes in visual field	This is assessed by Goldmann perimetry and microperimetry; measurements before and after vector delivery are compared.	Baseline and up to 2 years following vector delivery
Secondary	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.	Baseline and 2 years following vector delivery

External Links

•   Study Website: Click here for more information about the study.