REP1 Gene Replacement Therapy for Choroideremia | NCT02407678

Studies
REP1 Gene Replacement Therapy for Choroideremia

NCT02407678

Sponsor

University of Oxford

Status

Completed

Last Update Posted

Aug 5, 2021Actual

Enrollment

30Estimated

Phase

Phase 2

Conditions

Choroideremia

Interventions

AAV-mediated REP1 gene replacement

Countries

United Kingdom

Protocol Section

Identification Module Status Module Sponsor/Collaborators Module Oversight Module Description Module Conditions Module Design Module Arms/Interventions Module Outcomes Module Eligibility Module Contacts/Locations Module References Module IPD Sharing Statement Module

Results Section

Participant Flow Module Baseline Characteristics Module Outcome Measures Module Adverse Events Module More Info Module

Annotation Section

Annotation Module

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module Condition Browse Module Intervention Browse Module

Protocol Section

Identification Module

NCT ID

Results Section

No data available

No data is available for this block.

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Version Holder

Status Module

Record Verification Date

Jul 2021

Overall Recruitment Status or Expanded Access Status

Completed

Last Known Status

Not provided

Delayed Posting

Not provided

Why Stopped

Not provided

Expanded Access Info

Start Date

Aug 16, 2016Actual

Primary Completion Date

Jul 23, 2021Actual

Completion Date

Jul 23, 2021Actual

First Submitted Date

Mar 10, 2015

First Submission Date that Met QC Criteria

Mar 30, 2015

First Posted Date

Apr 3, 2015Estimated

Results Waived

Not provided

Results First Submitted Date

Not provided

Results First Submitted that Met QC Criteria

Not provided

Results First Posted Date

Not provided

Certification/Extension (aka Delayed Results) First Submitted Date

Not provided

Certification/Extension First Submitted that Passed QC Review

Not provided

Certification/Extension First Posted Date

Not provided

Last Update Submitted Date

Aug 4, 2021

Last Update Posted Date

Aug 5, 2021Actual

Name	Class
Moorfields Eye Hospital NHS Foundation Trust	OTHER
University College, London	OTHER

Oversight Module

Has Data Monitoring Committee (DMC)

Yes

Is FDA Regulated Drug

Not provided

Is FDA Regulated Device

Not provided

Is Unapproved Device

Not provided

Pediatric Postmarket Surveillance of a Device Product

Not provided

Product Exported from US

Not provided

FDAAA801 Violation

Not provided

Description Module

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.

Detailed Description

Not provided

Design Module

Study Type

Interventional

Number of References to an Expanded Access Study

Not provided

Expanded Access Types

Not provided

Patient Registry

Not provided

Target Follow-Up Duration

Not provided

Phases

Phase 2

Interventional Study Design

Allocation

Biospecimen

No data available

No data is available for this block.

Enrollment

30Estimated

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Treatment	Experimental	Treated eye undergoes AAV-mediated REP1 gene replacement. AAV vector is delivered by subretinal injection.	Genetic: AAV-mediated REP1 gene replacement
Control	No Intervention	Untreated eye

Interventions

Name	Type	Description	Arm Group Labels	Other Names
AAV-mediated REP1 gene replacement	Genetic	AAV vector carrying human REP1 gene is delivered into the treated eye by subretinal injection	Treatment

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change from baseline in best corrected visual acuity in the treated eye		2 years

Secondary Outcomes

Measure	Description	Time Frame
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

Other Outcomes

Not provided

Eligibility Module

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.

Accepts Healthy Volunteers

Sex

Male

Sex/Gender Based

Not provided

Sex/Gender Description

Not provided

Minimum Age

18 Years

Maximum Age

90 Years

Standard Ages

AdultOlder Adult

Study Population

Not provided

Sampling Method

Not provided

Contacts/Locations Module

Central Contacts

Not provided

Overall Officials

Name	Affiliation	Role
Robert E MacLaren, MB ChB DPhil	University of Oxford	Principal Investigator

Locations

Facility	Status	City	State	ZIP	Country	Contacts
Moorfields Eye Hospital NHS Foundation Trust		London		EC1V 2PD	United Kingdom
Oxford University Hospitals NHS Foundation Trust

Condition Browse Module

MeSH Terms

ID	Term
D015794	Choroideremia

Ancestor Terms

ID	Term
D015785	Eye Diseases, Hereditary
D005128	Eye Diseases
D015862	Choroid Diseases
D014603	Uveal Diseases

Browse Leaves

Not provided

Browse Branches

Not provided

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.

Masking Info

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.

Who Masked

Not provided