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Gene Therapy for Blindness Caused by Choroideremia

Sponsor
University of Oxford (Other)
Overall Status
Completed
CT.gov ID
NCT01461213
Collaborator
Oxford University Hospitals NHS Trust (Other), Moorfields Eye Hospital NHS Foundation Trust (Other), University College, London (Other), Manchester University NHS Foundation Trust (Other), University of Manchester (Other), University Hospital Southampton NHS Foundation Trust (Other), University of Southampton (Other)
14
Enrollment
4
Locations
2
Arms
72
Duration (Months)
3.5
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

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

Study Design

Study Type:
Interventional
Actual Enrollment :
14 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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 Start Date :
Oct 1, 2011
Actual Primary Completion Date :
Oct 1, 2017
Actual Study Completion Date :
Oct 1, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: Dose 1

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
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.
Other Names:
  • Adeno-associated viral vector

    		•
    Experimental: 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.

    Drug: 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.
    Other Names:
  • Adeno-associated viral vector

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Visual acuity [6 months]

      Best corrected visual acuity, following cataract surgery if indicated

    Secondary Outcome Measures

    1. Microperimetry, OCT and fundus autofluorescence [24 months]

      Structure function correlations at the margins of the retinal degeneration

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Moorfields Eye Hospital NHS Foundation Trust London United Kingdom EC1V 2PD
    2 St Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust Manchester United Kingdom M13 9WL
    3 Oxford Radcliffe Hospitals NHS Trust Oxford United Kingdom OX3 9DU
    4 Eye Unit, Southampton University Hospitals NHS Trust Southampton United Kingdom SO16 6YD

    Sponsors and Collaborators

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

    Investigators

    • Study Chair: Robert E MacLaren, MB ChB DPhil, University of Oxford, Oxford Radcliffe Hospitals NHS Trust and Moorfields Eye Hospital
    • Principal Investigator: 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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    University of Oxford
    ClinicalTrials.gov Identifier:
    NCT01461213
    Other Study ID Numbers:
    • CHM09/01
    • 2009-014617-27
    First Posted:
    Oct 28, 2011
    Last Update Posted:
    Nov 17, 2017
    Last Verified:
    Nov 1, 2017
    Keywords provided by University of Oxford
    Tapetoretinal degeneration, choroideraemia, X-linked
    retinitis pigmentosa
    Additional relevant MeSH terms:
    Choroideremia

    Study Results

    No Results Posted as of Nov 17, 2017