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.
Name: QR-1123
Name: Sham procedure
Description: Incidence and severity of ocular adverse events scored based on CTCAC in the study and fellow eye
Measure: Incidence and Severity of ocular AEs Time: up to 12 monthsDescription: Incidence and severity of non-ocular adverse events scored based on CTCAC in the study and fellow eye
Measure: Incidence and Severity of non-ocular AEs Time: up to 12 monthsDescription: Changes in Best corrected visual acuity (BCVA)
Measure: Changes in BCVA Time: up to 12 monthsDescription: Changes in Low-luminance visual acuity (LLVA)
Measure: Changes in LLVA Time: up to 12 monthsDescription: Changes in Dark adapted chromatic (DAC) perimetry
Measure: Changes in DAC perimetry Time: up to 12 monthsDescription: Changes in Static VF (Visual Field)
Measure: Changes in Static VF Time: up to 12 monthsDescription: Changes in Microperimetry
Measure: Changes in Microperimetry Time: up to 12 monthsDescription: Changes in Spectral Domain-Optical Coherence Tomography
Measure: Changes in SD-OCT Time: up to 12 monthsDescription: Changes in Full-field Stimulus Threshold (FST)
Measure: Changes in FST Time: up to 12 monthsDescription: Changes in Full-field Electroretinogram (ERG)
Measure: Changes in Full-field ERG Time: up to 12 monthsDescription: Serum levels of QR-1123
Measure: Assessment of systemic exposure after treatment with QR-1123 Time: up to 12 monthsAllocation: Randomized
Sequential Assignment
There is one SNP
A Prospective First-In-Human Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa (adRP) Due to the P23H Mutation in the RHO Gene. --- P23H ---
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. --- P23H ---
4. A molecular diagnosis of autosomal dominant form of RP with the P23H mutation in the RHO gene, based on genetic analysis. --- P23H ---
Main Exclusion Criteria: 1. 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). --- P23H ---
Autosomal Dominant Retinitis Pigmentosa Eye Diseases Eye Diseases, Hereditary Retinal Dystrophies Retinal Disease Retinitis Vision Tunnel Vision Disorders Arthrogryposis Vision Disorders Eye Diseases Retinitis Retinitis Pigmentosa Retinal Diseases Retinal Dystrophies Eye Diseases, Hereditary Genetic Diseases, Inborn 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. --- P23H ---
Autosomal Dominant Retinitis Pigmentosa Eye Diseases Eye Diseases, Hereditary Retinal Dystrophies Retinal Disease Retinitis Vision Tunnel Vision Disorders Arthrogryposis Vision Disorders Eye Diseases Retinitis Retinitis Pigmentosa Retinal Diseases Retinal Dystrophies Eye Diseases, Hereditary Genetic Diseases, Inborn 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. --- P23H --- --- P23H ---
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. --- P23H ---
Restoration of WT RHO function is expected to improve vision in patients with adRP due to the P23H mutation. --- P23H ---