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Gene Therapy for Blindness Caused by Choroideremia

Primary Purpose

Choroideremia

Status

Completed

Phase

Phase 1

Locations

United Kingdom

Study Type

Interventional

Intervention

rAAV2.REP1

About this trial

This is an interventional treatment trial for Choroideremia focused on measuring Tapetoretinal degeneration, choroideraemia, X-linked, retinitis pigmentosa

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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.

Sites / Locations

Moorfields Eye Hospital NHS Foundation Trust
St Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust
Oxford Radcliffe Hospitals NHS Trust
Eye Unit, Southampton University Hospitals NHS Trust

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Dose 1

Dose 2

Arm Description

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

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

Outcomes

Primary Outcome Measures

Visual acuity

Best corrected visual acuity, following cataract surgery if indicated

Secondary Outcome Measures

Microperimetry, OCT and fundus autofluorescence

Structure function correlations at the margins of the retinal degeneration

Full Information

NCT ID

NCT01461213

First Posted

October 21, 2011

Last Updated

November 16, 2017

Sponsor

University of Oxford

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT01461213

Brief Title

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

2. Study Status

Record Verification Date

November 2017

Overall Recruitment Status

Completed

Study Start Date

October 2011 (undefined)

Primary Completion Date

October 2017 (Actual)

Study Completion Date

October 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Oxford

Collaborators

4. Oversight

Data Monitoring Committee

Yes

5. 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.

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Choroideremia

Keywords

Tapetoretinal degeneration, choroideraemia, X-linked, retinitis pigmentosa

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

14 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dose 1

Arm Type

Experimental

Arm Description

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

Arm Title

Dose 2

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

rAAV2.REP1

Other Intervention Name(s)

Adeno-associated viral vector

Intervention Description

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.

Primary Outcome Measure Information:

Title

Visual acuity

Description

Best corrected visual acuity, following cataract surgery if indicated

Time Frame

6 months

Secondary Outcome Measure Information:

Title

Microperimetry, OCT and fundus autofluorescence

Description

Structure function correlations at the margins of the retinal degeneration

Time Frame

24 months

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Overall Study Officials: