Gene therapy for treatment of choroideremia

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

Contact information

Study information

Eligibility

Locations

Countries of recruitment

• England
• United Kingdom

Study participating centres

Sponsor information

NIHR Evaluation, Trials and Studies Coordinating Centre (NETSCC)
University/education

University of Southampton
Alpha House
Enterprise Road
Southampton
SO16 7NS
England
United Kingdom

"ROR"	https://ror.org/03d7d0579

Funders

Funder type

Government

Results and Publications

Study outputs

Editorial Notes

05/06/2024: Publication reference added.
01/09/2023: The intention to publish date has been changed from 31/03/2023 to 31/03/2024.
09/01/2023: The intention to publish date has been changed from 31/01/2023 to 31/03/2023.
23/08/2022: Protocol added.
05/07/2022: The intention to publish date was changed from 31/07/2022 to 31/01/2023.
07/07/2021: The publication and dissemination plan has been updated.
05/07/2019: The total final enrolment was added.
02/04/2019: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/03/2019 to 30/06/2019.
2. The overall trial end date was changed from 31/12/2020 to 31/07/2021.
3. The intention to publish date was changed from 30/06/2021 to 31/07/2022.
4. IPD sharing statement added.
02/04/2019: The condition has been changed from "Specialty: Ophthalmology, Primary sub-specialty: ; UKCRC code/ Disease:" to "Choroideremia" following a request from the NIHR.
04/10/2018: The recruitment end date has been changed from 31/08/2018 to 31/03/2019.
13/12/2017: Internal review.
11/12/2017: The recruitment end date was changed from 12/12/2016 to 31/08/2018. The overall trial end date was changed from 12/12/2016 to 31/12/2020. The intention to publish date was changed from 12/12/2017 to 30/06/2021.
11/03/2016: Internal review