Plain English Summary
Background and study aims
Choroideremia is a rare incurable inherited disorder that almost exclusively affects males. It causes progressive loss of vision (sight) due to degeneration of the choroids (cells that are essential for sight) and retina (light-sensitive area at the back of the eye). The disease is caused by a defect in a certain gene located on the X-chromosome (i.e. the sex chromosome), and this is why the disease affects men and women differently. Women have two X-chromosomes and so a normal gene on one Xchromosome can compensate for a defective gene on the other Xchromosome to some extent. Men, however, only have one Xchromosome. Sight loss in choroideremia begins with ‘night blindness’ (i.e. loss of night vision) in adolescence, followed by a gradual loss of peripheral vision which results in progressively worsening ‘tunnel vision’. Ultimately, central vision is lost by the fourth or fifth decade. There are currently no treatments available that can successfully treat choroideremia, but a new gene therapy technique has been developed which may help to slow or even stop the degeneration. The new technique involves putting normal copies of the affected gene back into the cells of the retina to help them to function normally. This is achieved by an operation to inject the normal genes into the retina, using a modified virus to carry the genes into the cells. The purpose of this study is to find out if vision can be preserved in patients suffering from choroideremia by replacing the defective gene using gene therapy. This study is the continuation of an earlier one which started in 2011, and which has shown encouraging results so far.
Who can participate?
Men aged at least 18 with choroideremia.
What does the study involve?
One eye of each participant in the study is treated with the gene therapy. This includes a surgical procedure where normal copies of the defective genes that cause choroideremia are injected into the retina. Each participant is then followed up over the next 24 months, comparing disease progression of the treated eye compared to the untreated one. The decision about which eye to treat is on clinical grounds and is generally the worse eye affected. The eye to be treated is randomised in cases where the degeneration is about the same in both eyes.
What are the possible benefits and risks of participating?
Possible benefits include the slowing down or possibly preventing further loss of sight in men affected by choroideremia. Side effects of the surgical procedure may include, pain and discomfort, infection or, more rarely, tearing or detachment of the retina and haemorrhage. Possible side effects of the gene therapy include inflammation or, more rarely, a severe immune response.
Where is the study run from?
1. Oxford Eye Hospital (UK)
2. Moorfields Eye Hospital, London (UK)
When is the study starting and how long is it expected to run for?
May 2016 to December 2020
Who is funding the study?
1. National Institute for Health Research (UK)
2. Medical Research Council (UK)
Who is the main contact?
Dr Marco Bellini
An open label Phase 2 clinical trial of retinal gene therapy for choroideremia using an adeno-associated viral vector (AAV2) encoding Rabescort protein 1 (REP1)
The aim of this study is to find out if it is possible to preserve vision in patients suffering from choroideremia by replacing the defective gene using gene therapy.
London - West London & GTAC Research Ethics Committee, 16/10/2015, ref: 15/LO/1379
Randomised; Interventional; Design type: Treatment, Gene Therapy
Primary study design
Secondary study design
Randomised controlled trial
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
AAV2.REP1, Adeno-associated viral vector (AAV2) encoding Rab-escort protein 1 (REP1)
One eye will receive the gene therapy. The efficacy of the gene therapy will be evaluated by comparing the progress of the disease over a period of 24 months in the treated eye and the untreated control eye. The decision about which eye to treat will be made on clinical grounds and will generally be the worse eye affected. The eye to be treated will be randomised in cases where the degeneration is relatively symmetrical between the two eyes.
Primary outcome measure
Change in best corrected visual acuity in the treated eye, assessed at baseline, day 7, month 1, month 3, month 6, month 9, month 12, month 18 and month 24
Secondary outcome measures
Change from baseline in other functional, immunological, physiological and anatomical outcomes in the treated eye pertaining to vector efficacy and safety, and safety of the surgical procedure
Overall trial start date
Overall trial end date
Reason abandoned (if study stopped)
Participant inclusion criteria
1. 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 equal to or worse than 6/6 (20/20; Decimal 1.0; LogMAR 0) but better than or equal to 6/60 (20/200; Decimal 0.1; LogMAR 1.0) in the study eye
Target number of participants
Planned Sample Size: 30; UK Sample Size: 30
Total final enrolment
Participant 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 minimum of 3 weeks
5. Unwillingness to use barrier contraception methods for a period of three months following gene therapy surgery, if relevant
6. Participation in another research study involving an investigational product in the preceding 12 weeks
Recruitment start date
Recruitment end date
Countries of recruitment
Trial participating centre
Oxford Eye Hospital
Lower Ground 1 West Wing John Radcliffe Hospital
Trial participating centre
Moorfields Eye Hospital
162 City Road
National Institute for Health Research
Funding Body Type
Funding Body Subtype
Medical Research Council
Funding Body Type
Funding Body Subtype
Results and Publications
Publication and dissemination plan
The results of the study will be published in international medical journals upon completion of the study.
IPD sharing statement
The datasets generated during and/or analysed during the current study are not expected to be made available as the data has been licensed to a biotech company, Nightstar Therapeutics (the supplier of the gene therapy being tested in this study), for their use in a future submission for regulatory approval.
Intention to publish date
Participant level data
Not expected to be available
Basic results (scientific)