RPGR NHC
Research type
Research Study
Full title
Natural History Study of Patients with X-linked Retinal Dystrophy Associated with Mutations in Retinitis Pigmentosa GTPase Regulator (RGPG)
IRAS ID
258944
Contact name
Michel Michaelides
Contact email
Sponsor organisation
MeiraGTx UK II Ltd
Clinicaltrials.gov Identifier
Duration of Study in the UK
6 years, 0 months, 0 days
Research summary
"Research Summary"
The purpose of this study is to undertake a detailed prospective phenotypic study of the natural history of retinal dystrophy caused by mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene. Mutations in the RPGR gene are a major cause of X-linked retinitis pigmentosa (XLRP), which is a severe form of retinitis pigmentosa with an early onset of night blindness (generally <10 years of age) and progression to legal blindness by the 3rd or 4th decade. Mutations in RPGR are also the most common cause of X-linked cone-rod dystrophy (XLCORD), where affected males develop onset of visual symptoms from the 2nd to 4th decade, and show progressive declines in central vision followed by declines in night vision, development of light sensitivity, and myopia. RPGR mutations have also been shown to be associated with X-linked recessive atrophic macular degeneration. Proof of principle studies for RPGR gene replacement therapy has been demonstrated with gene replacement in an RPGR mouse model.Human clinical trials are now underway. We intend to undertake a detailed prospective phenotypic study to investigate the natural history of RPGR. Detailed phenotyping of patients with RPGR mutations should facilitate the identification of an optimal window for intervention, provide specific parameters to quantify treatment effects and define clinical endpoints, and will help identify suitable patients for therapeutic intervention.
"Summary of Results"
What is RPGR-associated X-linked Retinal Dystrophy?
RPGR-associated X-linked retinal dystrophy is an inherited condition caused by changes in a gene called RPGR (Retinitis Pigmentosa GTPase Regulator) and gets worse over time. Symptoms usually start in childhood or early adulthood. Those affected first have trouble seeing at night. Later, peripheral vision is lost, and patients experience tunnel vision.Who participated in this study?
People with RPGR-associated X-linked (meaning that it occurs on the X chromosome) retinal dystrophy. Retinal dystrophy includes several genetic conditions that result in vision loss. In some cases, retinal dystrophy involves a variant of the RPGR (Retinitis Pigmentosa GTPase Regulator) gene. To be included in this study, individuals needed to have a permanent change in the RPGR gene that results in progressive vision loss (i.e., loss of vision that gets worse over time).Males or females aged 5 years or older with RPGR-associated X-linked retinal dystrophy were allowed to take part in the study.
Who was not allowed to participate in the study?
Those who did not have RPGR-associated progressive vision loss or who had RPGR-associated progressive vision loss but were under 5 years of age were not allowed to take part in the study.A total of 119 individuals with RPGR-associated progressive vision loss took part in the study, of whom 84 were 18 years or older and 35 were below 18 years.
What treatment did the participants receive?
Participants did not receive treatment, but were followed over time to understand how the condition progresses without any specific treatment.Why was the study done?
The main purpose of the study was to understand how RPGR-associated X-linked retinal dystrophy develops and progresses over time. The main study objectives were to:
* Identify a group of individuals with variants in the RPGR gene for an in-depth clinical and imaging-related characterization
* Investigate disease progression
* Investigate the relationship between retinal structure and retinal functionWhat was the design of the study?
This was an observational study conducted at multiple sites in the United States, the United Kingdom, and Canada that evaluated participants with RPGR-associated X-linked progressive vision loss. It was planned to follow study participants for up to 5 years.Results of the study:
A total of 119 participants with RPGR-associated X-linked progressive vision loss were included in the study. Overall, the study showed changes in some of the tests performed that are consistent with those observed previously in similar patient groups and are expected based on our understanding of the disorder, but also some assessments for which the results remained relatively unchanged throughout the study. Changes in the sensitivity of the retina (the light-sensitive cells at the back of the eye) to light and changes to the structure of the retina that show progression of the disorder all showed changes as early as 6 months after enrolment, which continued to worsen over time. Assessments of how clear the central vision is did not show a meaningful decline over time, indicating that the disorder primarily affects peripheral vision (your ability to see what's around you, to the sides, or "out of the corner of your eye," without moving your head or eyes). The study also showed that this disorder typically impacts both eyes equally.What were the side effects?
As participants did not receive treatment in this study, no side effects (i.e., health problems that might be related to treatment according to the study investigator) were reported.How has this study helped patients and researchers?
The results of this study helped researchers to provide more accurate advice to patients. The results also help in identifying potential participants for future clinical trials, selecting optimal time points for treatment, and determining appropriate study endpoints.Where can I learn more about this study?
Results of clinical studies may be available to the public in different places. Note that results presented in different places may use different methods of displaying the results.
If you want more information on the study, you can perform an internet search using the product or study identifiers. Below you can find the list of identifiers used:
- MGT011 (Sponsor Study Number)
- NCT03349242 (Trial number on https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fclinicaltrials.gov%2F&data=05%7C02%7CWales.REC7%40wales.nhs.uk%7Cc2ec0ff34d3e41d405ed08de1d42f1d8%7Cbb5628b8e3284082a856433c9edc8fae%7C0%7C0%7C638980370547978643%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=V8dk9A3GbZV89VBPUQ8vwaz4315KXtrdI9v74yu8ih8%3D&reserved=0)
You can find more information in English about this study on the following website:
- https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Fclinicaltrials.gov%2FNBTI%2FiAXBAQ%2FAQ%2F87774ab9-8747-47ee-aaf2-6a4e6855a681%2F1%2FHZcqicW4mB&data=05%7C02%7CWales.REC7%40wales.nhs.uk%7Cc2ec0ff34d3e41d405ed08de1d42f1d8%7Cbb5628b8e3284082a856433c9edc8fae%7C0%7C0%7C638980370548022619%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=GubjaBccM719xRM%2FEiHYDzPQs03FALVLp5I9w%2BoSdn8%3D&reserved=0Who carried out the study?
Sponsor: MeiraGTx UK II Ltd
How to contact: patients@meiragtx.comREC name
Wales REC 7
REC reference
19/WA/0065
Date of REC Opinion
7 Mar 2019
REC opinion
Further Information Favourable Opinion