QR-110 in Subjects with Leber's Congenital Amaurosis (LCA)
Research type
Research Study
Full title
A Double-Masked, Randomized, Controlled, Multiple-Dose Study to Evaluate the Efficacy, Safety, Tolerability and Systemic Exposure of QR-110 in Subjects with Leber's Congenital Amaurosis (LCA) due to c.2991+1655A>G Mutation (p.Cys998X) in the CEP290 Gene
IRAS ID
261274
Contact name
Michel Michaelides
Contact email
Sponsor organisation
ProQR Therapeutics
Eudract number
2018-003501-25
Clinicaltrials.gov Identifier
N/A, N/A
Duration of Study in the UK
2 years, 10 months, 0 days
Research summary
Research Summary
Leber’s congenital amaurosis (LCA) is a severe inherited retinal degenerative disease resulting in blindness, often in early childhood.
Patients show severe vision disturbances from an early age and slow progressive loss of remaining vision.
Currently there is no approved treatment for LCA10. The study drug is designed to repair the problem that causes LCA10. This may stop or possibly reverse some effects of LCA10. This study is being done to find out if the study drug works and is safe in patients with LCA10. Approximately 30 - 60 adults and children (aged 8 years and older) are planned to participate in the study.
Available safety and efficacy data from study PQ-110-001, a Phase 1b/2, first-in-human study to evaluate the safety and tolerability of QR-110, support the therapeutic potential observed in the nonclinical studies, and warrant the initiation of additional trials to confirm risk benefit.
Study PQ-110-003 will test the efficacy and safety of QR-110 at 2 dose levels.
Summary of Results
Thirty-six subjects (over 8 years of age), with impaired vision due to a particular type of Leber Congenital Amaurosis (LCA), caused by one or more mutations (defects) in their DNA participated in this study.
What treatments or interventions did the participants take/receive?
The study investigated whether the study drug, sepofarsen (QR-110), could slow or stop the worsening of vision loss and whether the study drug is safe. The study drug was given in 2 different doses and was compared against a sham (dummy) procedure. The study drug was given through an injection in the eye.What medical problems (adverse reactions) did the participants have?
There were no ocular (eye) or non-ocular (non-eye) side effects reported leading to study discontinuation; however 7 subjects (6 taking sepofarsen and 1 sham) either temporarily or permanently discontinued treatment due to side effects. There were no ocular or non-ocular side effects reported leading to death. Ocular side effects were observed in all 36 subjects and were mostly mild to moderate in severity.What happened during the study?
The study was stopped early by the Sponsor. The decision to stop the study was not due to any changes in the medical condition or health of the subjects who participated, nor for any other safety issue. In total 36 subjects joined the study; 24 received the study drug at 2 different doses and 12 received the dummy treatment.What were the results of the study?
No statistically significant differences were observed at 12 months between the sepofarsen treated and sham groups for the endpoints designed to show if it works. Sepofarsen was safe and well-tolerated in most subjects; however, retinal degeneration with reduction in vision were reported as side effects in one subject, and cataract-related events were also reported during the study. Overall, the safety and tolerability of sepofarsen was acceptable.How has this study helped subjects and researchers?
More research will be needed to know if treatment with the study drug will be safe and may potentially slow down or stop the worsening of vision loss in subjects with a specific form of LCA.What are the details surrounding further research?
At present there is no future research planned. Subjects that participated in the study will be offered an opportunity to continue treatment in a post-trial access program, if allowed in their country, and if in their best interest.Where can I learn more about this study?
You can find out more information on https://eur03.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrials.gov%2F&data=05%7C01%7Capprovals%40hra.nhs.uk%7Cf4a4b4bb76444681f72508daddc65f9a%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638066141320345641%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=3bT%2Fg0jfkZ0VbREhhXTe%2Fh%2FLIOm5e7biSuwOwkfngh4%3D&reserved=0 and search on study number: NCT03913143.REC name
London - City & East Research Ethics Committee
REC reference
19/LO/0522
Date of REC Opinion
31 May 2019
REC opinion
Further Information Favourable Opinion