Clinical trial NCT01461213: Gene Therapy for Blindness Caused by Choroideremia
Official title: An Open Label Dose Escalation Phase 1 Clinical Trial of Retinal Gene Therapy for Choroideraemia Using an Adeno-associated Viral Vector (AAV2) Encoding Rab-escort Protein 1 (REP1)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Choroideremia
Keywords: Tapetoretinal degeneration, choroideraemia, X-linked
retinitis pigmentosa
Lead sponsor: University of Oxford
Sponsor class: OTHER
Collaborators: name: Oxford University Hospitals NHS Trust
name: Moorfields Eye Hospital NHS Foundation Trust
name: University College, London
name: Manchester University NHS Foundation Trust
name: University of Manchester
name: University Hospital Southampton NHS Foundation Trust
name: University of Southampton
First posted: 2011-10-28
Enrollment: 14
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: - Primary objective: To assess the safety and tolerability of the AAV.REP1 vector, administered at two different doses to the retina in 12 patients with a diagnosis of choroideremia.

- Secondary Objective: To identify any therapeutic benefit as evidenced by a slowing down of the retinal degeneration assessed by functional and anatomical methods in the treated eye compared to the control eye 24 months after gene delivery.

Detailed description: Detailed description may be found in the following scientific publication:

Retinal gene therapy in patients with choroideremia: initial findings from a phase 1/2 clinical trial, The Lancet, Volume 383, Issue 9923, Pages 1129 - 1137 (29 March 2014).

Links: www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)62117-0/abstract ; http://dx.doi.org/doi:10.1016/S0140-6736(13)62117-0

Eligibility criteria: Inclusion Criteria:

* Participant is willing and able to give informed consent for participation in the study,
* Male aged 18 years or above,
* Diagnosed with choroideraemia and in good health,
* Active disease with SLO changes visible within the macula region,
* Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the study,
* Vision at least 6/60 or better in the study eye.

Exclusion Criteria:

* Female and child participants (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 disease or other ocular morbidity which might confound use of the fellow eye as a long-term control,
* Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study,
* Participants who have participated in another research study involving an investigational product in the previous 12 weeks.

Primary outcomes:
measure: Visual acuity
timeFrame: 6 months
Secondary outcomes:
measure: Microperimetry, OCT and fundus autofluorescence
timeFrame: 24 months
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Moorfields Eye Hospital NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: St Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust
city: Oxford
country: United Kingdom
facility: Oxford Radcliffe Hospitals NHS Trust
city: Southampton
country: United Kingdom
facility: Eye Unit, Southampton University Hospitals NHS Trust
Study officials:
affiliation: University of Oxford, Oxford Radcliffe Hospitals NHS Trust and Moorfields Eye Hospital
name: Robert E MacLaren, MB ChB DPhil
role: STUDY_CHAIR
affiliation: Imperial College London
name: Miguel C Seabra, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: UCL Institute of Ophthalmology and Moorfields Eye Hospital
name: Andrew R Webster, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Oxford University Hospitals NHS Trust
name: Susan M Downes, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Manchester and Central Manchester University Hospitals NHS Foundation Trust
name: Graeme C Black, MB BCh DPhil
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Southampton and Southampton University Hospitals Trust
name: Andrew J Lotery, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Oxford
name: Len W Seymour, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Imperial College London
name: Tanya Tolmachova, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Simunovic MP, Jolly JK, Xue K, Edwards TL, Groppe M, Downes SM, MacLaren RE. The Spectrum of CHM Gene Mutations in Choroideremia and Their Relationship to Clinical Phenotype. Invest Ophthalmol Vis Sci. 2016 Nov 1;57(14):6033-6039. doi: 10.1167/iovs.16-20230.
citation: Xue K, Oldani M, Jolly JK, Edwards TL, Groppe M, Downes SM, MacLaren RE. Correlation of Optical Coherence Tomography and Autofluorescence in the Outer Retina and Choroid of Patients With Choroideremia. Invest Ophthalmol Vis Sci. 2016 Jul 1;57(8):3674-84. doi: 10.1167/iovs.15-18364.
citation: Seitz IP, Zhour A, Kohl S, Llavona P, Peter T, Wilhelm B, Zrenner E, Ueffing M, Bartz-Schmidt KU, Fischer MD. Multimodal assessment of choroideremia patients defines pre-treatment characteristics. Graefes Arch Clin Exp Ophthalmol. 2015 Dec;253(12):2143-50. doi: 10.1007/s00417-015-2976-4. Epub 2015 Mar 7.
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.