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REP1 Gene Replacement Therapy for Choroideremia (REGENERATE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02407678
Recruitment Status : Active, not recruiting
First Posted : April 3, 2015
Last Update Posted : July 2, 2019
Sponsor:
Collaborators:
Moorfields Eye Hospital NHS Foundation Trust
University College, London
Information provided by (Responsible Party):
University of Oxford

Tracking Information
First Submitted Date  ICMJE March 10, 2015
First Posted Date  ICMJE April 3, 2015
Last Update Posted Date July 2, 2019
Actual Study Start Date  ICMJE August 2016
Estimated Primary Completion Date August 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 26, 2016)
Change from baseline in best corrected visual acuity in the treated eye [ Time Frame: 2 years ]
Original Primary Outcome Measures  ICMJE
 (submitted: March 30, 2015)
Change from baseline in best corrected visual acuity in treated eye, compared to untreated control eye [ Time Frame: 2 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 26, 2016)
  • Change from baseline in the central visual field in the treated eye as determined by microperimetry [ Time Frame: 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 [ Time Frame: 2 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 30, 2015)
  • Change from baseline in autofluorescence evaluation in treated eye, compared to untreated control eye [ Time Frame: 2 years ]
  • Change from baseline in central visual field using microperimetry readings in treated eye, compared to untreated control eye [ Time Frame: 2 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE REP1 Gene Replacement Therapy for Choroideremia
Official Title  ICMJE 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)
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
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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.

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
Condition  ICMJE Choroideremia
Intervention  ICMJE Genetic: AAV-mediated REP1 gene replacement
AAV vector carrying human REP1 gene is delivered into the treated eye by subretinal injection
Study Arms  ICMJE
  • Experimental: Treatment
    Treated eye undergoes AAV-mediated REP1 gene replacement. AAV vector is delivered by subretinal injection.
    Intervention: Genetic: AAV-mediated REP1 gene replacement
  • No Intervention: Control
    Untreated eye
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: March 30, 2015)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2021
Estimated Primary Completion Date August 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Candidate is willing and able to give informed consent for participation in the study.
  2. Male aged 18 years or above.
  3. Genetic or molecular confirmed diagnosis of choroideremia (REP1 protein deficiency).
  4. Active disease visible clinically within the macula region.
  5. 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:

  1. Any female, or a male aged below 18 years.
  2. An additional cause for sight loss (e.g. amblyopia) in the eye to be treated.
  3. 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.
  4. Inability to take systemic prednisolone for a period of 45 days.
  5. Unwillingness to use barrier contraception methods for a period of three months following gene therapy surgery.
  6. Participation in another research study involving an investigational product in the preceding 12 weeks.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02407678
Other Study ID Numbers  ICMJE REGEN2015
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Oxford
Study Sponsor  ICMJE University of Oxford
Collaborators  ICMJE
  • Moorfields Eye Hospital NHS Foundation Trust
  • University College, London
Investigators  ICMJE
Principal Investigator: Robert E MacLaren, MB ChB DPhil University of Oxford
PRS Account University of Oxford
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP