REGENERATE: REP1 Gene Replacement Therapy for Choroideremia

Sponsor

University of Oxford (Other)

Overall Status

Completed

CT.gov ID

NCT02407678

Collaborator

Moorfields Eye Hospital NHS Foundation Trust (Other), University College, London (Other)

Enrollment

Locations

Arms

59.2

Actual Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Choroideremia	Genetic: AAV-mediated REP1 gene replacement	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention 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.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.

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Aug 16, 2016

Actual Primary Completion Date :

Jul 23, 2021

Actual Study Completion Date :

Jul 23, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment Treated eye undergoes AAV-mediated REP1 gene replacement. AAV vector is delivered by subretinal injection.	Genetic: AAV-mediated REP1 gene replacement AAV vector carrying human REP1 gene is delivered into the treated eye by subretinal injection
No Intervention: Control Untreated eye

Arm

Intervention/Treatment

Experimental: Treatment

Treated eye undergoes AAV-mediated REP1 gene replacement. AAV vector is delivered by subretinal injection.

Genetic: AAV-mediated REP1 gene replacement

AAV vector carrying human REP1 gene is delivered into the treated eye by subretinal injection

No Intervention: Control

Untreated eye

Outcome Measures

Primary Outcome Measures

Change from baseline in best corrected visual acuity in the treated eye [2 years]

Secondary Outcome Measures

Change from baseline in the central visual field in the treated eye as determined by microperimetry [2 years]
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 [2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 90 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Moorfields Eye Hospital NHS Foundation Trust	London		United Kingdom	EC1V 2PD
2	Oxford University Hospitals NHS Foundation Trust	Oxford		United Kingdom	OX3 9DU

Sponsors and Collaborators

University of Oxford
Moorfields Eye Hospital NHS Foundation Trust
University College, London

Investigators

Principal Investigator: Robert E MacLaren, MB ChB DPhil, University of Oxford

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

University of Oxford

ClinicalTrials.gov Identifier:

NCT02407678

Other Study ID Numbers:

REGEN2015

First Posted:

Apr 3, 2015

Last Update Posted:

Aug 5, 2021

Last Verified:

Jul 1, 2021

Additional relevant MeSH terms:

Choroideremia

Study Results

No Results Posted as of Aug 5, 2021