Back to resultsREP1 Gene Replacement Therapy for Choroideremia (REGENERATE)
Primary Purpose
Choroideremia
Status
Completed
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
AAV-mediated REP1 gene replacement
Sponsored by
About this trial
This is an interventional treatment trial for Choroideremia
Eligibility Criteria
Inclusion Criteria:
- Candidate is willing and able to give informed consent for participation in the study.
- Male aged 18 years or above.
- Genetic or molecular confirmed diagnosis of choroideremia (REP1 protein deficiency).
- Active disease visible clinically within the macula region.
- Best corrected visual acuity better than or equal to 6/60 (20/200; Decimal 0.1; LogMAR 1.0) in the study eye.
Exclusion Criteria:
- Any female, or a male aged below 18 years.
- An additional cause for sight loss (e.g. amblyopia) in the eye to be treated.
- Any other significant ocular and non-ocular disease or disorder which, in the opinion of the investigator, may put the participants at risk because of participation in the study.
- Inability to take systemic prednisolone for a period of 45 days.
- Unwillingness to use barrier contraception methods for a period of three months following gene therapy surgery.
- Participation in another research study involving an investigational product in the preceding 12 weeks.
Sites / Locations
- Moorfields Eye Hospital NHS Foundation Trust
- Oxford University Hospitals NHS Foundation Trust
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Treatment
Control
Arm Description
Treated eye undergoes AAV-mediated REP1 gene replacement. AAV vector is delivered by subretinal injection.
Untreated eye
Outcomes
Primary Outcome Measures
Change from baseline in best corrected visual acuity in the treated eye
Secondary Outcome Measures
Change from baseline in the central visual field in the treated eye as determined by microperimetry
Change from baseline in the area of surviving retinal pigment epithelium in the treated eye as measured by fundus autofluorescence, compared to the untreated fellow eye (control eye) after randomisation of treatment to one eye or the other
Full Information
NCT ID
NCT02407678
First Posted
March 10, 2015
Last Updated
August 4, 2021
Sponsor
University of Oxford
Collaborators
Moorfields Eye Hospital NHS Foundation Trust, University College, London
1. Study Identification
Unique Protocol Identification Number
NCT02407678
Brief Title
REP1 Gene Replacement Therapy for Choroideremia
Acronym
REGENERATE
Official Title
An Open Label Phase 2 Clinical Trial of Retinal Gene Therapy for Choroideremia Using an Adeno-associated Viral Vector (AAV2) Encoding Rab-escort Protein 1 (REP1)
Study Type
Interventional
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
August 16, 2016 (Actual)
Primary Completion Date
July 23, 2021 (Actual)
Study Completion Date
July 23, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Oxford
Collaborators
Moorfields Eye Hospital NHS Foundation Trust, University College, London
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The assessment of the efficacy (with respect to preservation of visual function and retinal structure) and safety of a single subretinal injection of AAV2.REP1 in participants with a confirmed diagnosis of choroideremia, as evaluated by various functional and anatomical outcomes measured over a number of time points up to 24 months post-treatment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Choroideremia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
The decision about which eye to treat will be made on clinical grounds and will generally be the worse eye affected in cases where BCVA differs between the two eyes by 2 lines or more of ETDRS letters. The eye to be treated will be randomised in cases where the degeneration is relatively symmetrical between the two eyes, defined as:
a difference in BCVA of no more than 1 line of ETDRS letters, and
no more than 25% difference in the area of surviving RPE as measured by fundus autofluorescence.
Prospective participants having non-symmetrical retinal degeneration will be allocated to the non-randomised arm. The treated eye will generally be the worse eye. Prospective participants having relatively symmetrical retinal degeneration will be allocated to the randomised arm.
Masking
None (Open Label)
Masking Description
The study is designated as Open Label with no masking. However, in order to minimise bias evaluation of the treated eye and untreated fellow eye (control eye), the ophthalmic assessments (visual acuity, microperimetry, fundus autofluorescence, etc.) will be conducted by an appropriately qualified masked observer once the participant's treated eye has had time to heal after the surgical procedure and has regained its normal appearance and function.
Allocation
Randomized
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment
Arm Type
Experimental
Arm Description
Treated eye undergoes AAV-mediated REP1 gene replacement. AAV vector is delivered by subretinal injection.
Arm Title
Control
Arm Type
No Intervention
Arm Description
Untreated eye
Intervention Type
Genetic
Intervention Name(s)
AAV-mediated REP1 gene replacement
Intervention Description
AAV vector carrying human REP1 gene is delivered into the treated eye by subretinal injection
Primary Outcome Measure Information:
Title
Change from baseline in best corrected visual acuity in the treated eye
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Change from baseline in the central visual field in the treated eye as determined by microperimetry
Time Frame
2 years
Title
Change from baseline in the area of surviving retinal pigment epithelium in the treated eye as measured by fundus autofluorescence, compared to the untreated fellow eye (control eye) after randomisation of treatment to one eye or the other
Time Frame
2 years
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Candidate is willing and able to give informed consent for participation in the study.
Male aged 18 years or above.
Genetic or molecular confirmed diagnosis of choroideremia (REP1 protein deficiency).
Active disease visible clinically within the macula region.
Best corrected visual acuity better than or equal to 6/60 (20/200; Decimal 0.1; LogMAR 1.0) in the study eye.
Exclusion Criteria:
Any female, or a male aged below 18 years.
An additional cause for sight loss (e.g. amblyopia) in the eye to be treated.
Any other significant ocular and non-ocular disease or disorder which, in the opinion of the investigator, may put the participants at risk because of participation in the study.
Inability to take systemic prednisolone for a period of 45 days.
Unwillingness to use barrier contraception methods for a period of three months following gene therapy surgery.
Participation in another research study involving an investigational product in the preceding 12 weeks.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert E MacLaren, MB ChB DPhil
Organizational Affiliation
University of Oxford
Official's Role
Principal Investigator
Facility Information:
Facility Name
Moorfields Eye Hospital NHS Foundation Trust
City
London
ZIP/Postal Code
EC1V 2PD
Country
United Kingdom
Facility Name
Oxford University Hospitals NHS Foundation Trust
City
Oxford
ZIP/Postal Code
OX3 9DU
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
REP1 Gene Replacement Therapy for Choroideremia
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