Gene Therapy for Blindness Caused by Choroideremia

NCT ID: NCT01461213

Last Updated: 2017-11-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

14 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-10-31

Study Completion Date

2017-10-31

Brief Summary

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\- 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

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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

Conditions

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Choroideremia

Keywords

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Tapetoretinal degeneration, choroideraemia, X-linked retinitis pigmentosa

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dose 1

Dose 1 = single subretinal injection of vector suspension containing approximately 10e10 rAAV2.REP1 genome particles. Six patients have now received Dose 1.

Group Type EXPERIMENTAL

rAAV2.REP1

Intervention Type DRUG

Single subretinal injection of rAAV2.REP1 vector suspension containing 10e12 genome particles per ml. Dose 1 = dose containing approximately 10e10 rAAV2.REP1 genome particles. Dose 2 = dose containing approximately 10e11 rAAV2.REP1 genome particles.

Dose 2

Dose 2 = single subretinal injection of vector suspension containing approximately 10e11 rAAV2.REP1 genome particles. Three patients thus far have received Dose 2.

Group Type EXPERIMENTAL

rAAV2.REP1

Intervention Type DRUG

Single subretinal injection of rAAV2.REP1 vector suspension containing 10e12 genome particles per ml. Dose 1 = dose containing approximately 10e10 rAAV2.REP1 genome particles. Dose 2 = dose containing approximately 10e11 rAAV2.REP1 genome particles.

Interventions

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rAAV2.REP1

Single subretinal injection of rAAV2.REP1 vector suspension containing 10e12 genome particles per ml. Dose 1 = dose containing approximately 10e10 rAAV2.REP1 genome particles. Dose 2 = dose containing approximately 10e11 rAAV2.REP1 genome particles.

Intervention Type DRUG

Other Intervention Names

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Adeno-associated viral vector

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Oxford University Hospitals NHS Trust

OTHER

Sponsor Role collaborator

Moorfields Eye Hospital NHS Foundation Trust

OTHER

Sponsor Role collaborator

University College, London

OTHER

Sponsor Role collaborator

Manchester University NHS Foundation Trust

OTHER_GOV

Sponsor Role collaborator

University of Manchester

OTHER

Sponsor Role collaborator

University Hospital Southampton NHS Foundation Trust

OTHER

Sponsor Role collaborator

University of Southampton

OTHER

Sponsor Role collaborator

University of Oxford

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Robert E MacLaren, MB ChB DPhil

Role: STUDY_CHAIR

University of Oxford, Oxford Radcliffe Hospitals NHS Trust and Moorfields Eye Hospital

Miguel C Seabra, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Imperial College London

Andrew R Webster, MD

Role: PRINCIPAL_INVESTIGATOR

UCL Institute of Ophthalmology and Moorfields Eye Hospital

Susan M Downes, MD

Role: PRINCIPAL_INVESTIGATOR

Oxford University Hospitals NHS Trust

Graeme C Black, MB BCh DPhil

Role: PRINCIPAL_INVESTIGATOR

University of Manchester and Central Manchester University Hospitals NHS Foundation Trust

Andrew J Lotery, MD

Role: PRINCIPAL_INVESTIGATOR

University of Southampton and Southampton University Hospitals Trust

Len W Seymour, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Oxford

Tanya Tolmachova, PhD

Role: PRINCIPAL_INVESTIGATOR

Imperial College London

Locations

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Moorfields Eye Hospital NHS Foundation Trust

London, , United Kingdom

Site Status

St Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust

Manchester, , United Kingdom

Site Status

Oxford Radcliffe Hospitals NHS Trust

Oxford, , United Kingdom

Site Status

Eye Unit, Southampton University Hospitals NHS Trust

Southampton, , United Kingdom

Site Status

Countries

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United Kingdom

References

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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.

Reference Type DERIVED
PMID: 27820636 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27403996 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25744334 (View on PubMed)

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.

Reference Type DERIVED
PMID: 24439297 (View on PubMed)

Other Identifiers

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2009-014617-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CHM09/01

Identifier Type: -

Identifier Source: org_study_id