Gene Therapy for Blindness Caused by Choroideremia

NCT01461213 | Completed Phase 1 DMC

• 2 other identifiers: CHM09/012009-014617-27
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 4

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.

Conditions

Choroideremia

Keywords

Tapetoretinal degeneration, choroideraemia, X-linked; retinitis pigmentosa

Outcome Measures

Primary Outcomes (1)

• Visual acuity

  Best corrected visual acuity, following cataract surgery if indicated

  6 months

Secondary Outcomes (1)

• Microperimetry, OCT and fundus autofluorescence

  24 months

Study Arms (2)

Dose 1

EXPERIMENTAL

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

Drug: rAAV2.REP1

Dose 2

EXPERIMENTAL

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

Drug: rAAV2.REP1

Interventions

rAAV2.REP1 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.

Also known as: Adeno-associated viral vector

Dose 1; Dose 2

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Oxford: lead
• Oxford University Hospitals NHS Trust: collaborator
• Moorfields Eye Hospital NHS Foundation Trust: collaborator
• University College, London: collaborator
• Manchester University NHS Foundation Trust: collaborator
• University of Manchester: collaborator
• University Hospital Southampton NHS Foundation Trust: collaborator
• University of Southampton: collaborator

Study Sites (4)

Moorfields Eye Hospital NHS Foundation Trust

London, EC1V 2PD, United Kingdom

Location

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

Manchester, M13 9WL, United Kingdom

Location

Oxford Radcliffe Hospitals NHS Trust

Oxford, OX3 9DU, United Kingdom

Location

Eye Unit, Southampton University Hospitals NHS Trust

Southampton, SO16 6YD, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 27820636 DERIVED

• 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.

  PMID: 27403996 DERIVED

• 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.

  PMID: 25744334 DERIVED

• 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 DERIVED

MeSH Terms

Conditions

Choroideremia; Retinitis Pigmentosa

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; Retinal Dystrophies; Retinal Degeneration; Retinal Diseases

Study Officials

• Robert E MacLaren, MB ChB DPhil

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

  STUDY CHAIR

• Miguel C Seabra, MD PhD

  Imperial College London

  PRINCIPAL INVESTIGATOR

• Andrew R Webster, MD

  UCL Institute of Ophthalmology and Moorfields Eye Hospital

  PRINCIPAL INVESTIGATOR

• Susan M Downes, MD

  Oxford University Hospitals NHS Trust

  PRINCIPAL INVESTIGATOR

• Graeme C Black, MB BCh DPhil

  University of Manchester and Central Manchester University Hospitals NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

• Andrew J Lotery, MD

  University of Southampton and Southampton University Hospitals Trust

  PRINCIPAL INVESTIGATOR

• Len W Seymour, PhD

  University of Oxford

  PRINCIPAL INVESTIGATOR

• Tanya Tolmachova, PhD

  Imperial College London

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: October 21, 2011
• First Posted: October 28, 2011
• Study Start: October 1, 2011
• Primary Completion: October 1, 2017
• Study Completion: October 1, 2017
• Last Updated: November 17, 2017

Record last verified: 2017-11

Locations

GB (4)