A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene
This study evaluates the safety, tolerability and efficacy of QR-1123 injection in the eye (intravitreal; IVT) injections (one eye/unilateral) in subjects receiving a single dose or repeat doses. Single injections will be assessed in an open label way, and repeat injections will be assessed in a double-masked, randomized, sham-controlled fashion.
- Autosomal Dominant Retinitis Pigmentosa
- Eye Diseases
- Eye Diseases, Hereditary
- Retinal Dystrophies
- Retinal Disease
- Vision Tunnel
- Vision Disorders
- Eligible Ages
- Over 18 Years
- Eligible Genders
- Accepts Healthy Volunteers
- Male or female, ≥ 18 years of age.
- Clinical presentation consistent with adRP, based on ophthalmic examinations.
- Impairment on VF in the opinion of the Investigator, as determined by perimetry.
- A molecular diagnosis of autosomal dominant form of RP with the P23H mutation in the RHO gene, based on genetic analysis.
- A clear ocular media and adequate pupillary dilation to permit good quality fundus imaging, as assessed by the Investigator.
- Presence of additional pathogenic mutations in genes (other than the P23H mutation in the RHO gene) associated with inherited retinal degenerative diseases or syndromes, based on genetic analysis (eg, Usher syndrome, Leber congenital amaurosis, etc).
- Presence of any significant ocular or non-ocular disease/disorder (including medication and laboratory test abnormalities) which, in the opinion of the Investigator and with concurrence of the Medical Monitor, may either put the subject at risk because of participation in the study, may influence the results of the study, or the subject's ability to participate in the study.
- Phase 1/Phase 2
- Study Type
- Intervention Model
- Sequential Assignment
- Primary Purpose
- Triple (Participant, Care Provider, Outcomes Assessor)
- Masking Description
- Single dose cohorts are open label. Repeat dose cohorts are randomized, double masked.
QR-1123 Single dose - dose level 1
|Open label Single dose cohort: dose level 1||
QR-1123 Single dose - dose level 2
|Open label Single dose cohort: dose level||
QR-1123 Single dose - dose level 3
|Open label Single dose cohort: dose level 3||
QR-1123 Single dose - dose level 4
|Open label Single dose cohort: dose level 4||
QR-1123 Single dose - dose level 5
|Open label Single dose cohort: dose level 5||
Repeat dose cohort 1
|Double-masked, randomized, sham controlled, Repeat dose cohort. Dose levels will be determined following DMC review of obtained safety and efficacy data.||
UK Center for Clinical and Translational Science and nearby locations
- NCT ID
- ProQR Therapeutics
Study ContactProQR Clinical Trial Manager
+31(0)88 166 7000
QR-1123 is an antisense oligonucleotide, designed to specifically target the mutant P23H messenger ribonucleic acid (mRNA) in order to reduce the expression of the P23H protein selectively, while preserving expression of the wild type (WT) rhodopsin (RHO) protein. It is hypothesized that the reduction of mutant P23H mRNA will reduce the deleterious effects of the dominant-negative protein and should result in increased function of WT rhodopsin protein in photoreceptors. Restoration of WT RHO function is expected to improve vision in patients with adRP due to the P23H mutation.
The study will comprise up to 8 single dose and repeat dose cohorts. Prior to initiating a higher single dose cohort and/or prior to initiating repeat dose cohort(s), available safety and efficacy data will be reviewed by the DMC.
In the single dose cohorts subjects will receive a single, unilateral IVT injection of QR-1123 in an open label fashion. In the repeat dose cohorts subjects will be randomized to receive either a unilateral IVT injection of QR-1123 every 3 months or a unilateral sham procedure every 3 months, in a double masked fashion. Subjects will be followed for safety, tolerability and efficacy for a total period of 12 months.