Clinical trial NCT04123626: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Autosomal Dominant Retinitis Pigmentosa
Eye Diseases
Eye Diseases, Hereditary
Retinal Dystrophies
Retinal Disease
Retinitis
Vision Tunnel
Vision Disorders
Keywords: adRP
Retinitis Pigmentosa
P23H mutation
Rhodopsin
antisense oligonucleotide
IVT
autosomal dominant
Lead sponsor: ProQR Therapeutics
Sponsor class: INDUSTRY
First posted: 2019-10-11
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Main Inclusion Criteria:

1. Male or female, ≥ 18 years of age.
2. Clinical presentation consistent with adRP, based on ophthalmic examinations.
3. Impairment on VF in the opinion of the Investigator, as determined by perimetry.
4. A molecular diagnosis of autosomal dominant form of RP with the P23H mutation in the RHO gene, based on genetic analysis.
5. A clear ocular media and adequate pupillary dilation to permit good quality fundus imaging, as assessed by the Investigator.

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).
2. 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.

Primary outcomes:
measure: Incidence and Severity of ocular AEs
timeFrame: up to 12 months
measure: Incidence and Severity of non-ocular AEs
timeFrame: up to 12 months
Secondary outcomes:
measure: Changes in BCVA
timeFrame: up to 12 months
measure: Changes in LLVA
timeFrame: up to 12 months
measure: Changes in DAC perimetry
timeFrame: up to 12 months
measure: Changes in Static VF
timeFrame: up to 12 months
measure: Changes in Microperimetry
timeFrame: up to 12 months
measure: Changes in SD-OCT
timeFrame: up to 12 months
measure: Changes in FST
timeFrame: up to 12 months
measure: Changes in Full-field ERG
timeFrame: up to 12 months
measure: Assessment of systemic exposure after treatment with QR-1123
timeFrame: up to 12 months
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Sue Anschutz-Rogers Eye Center, University of Colorado - Dept. of Ophthalmology
state: Colorado
city: Gainesville
country: United States
facility: VitreoRetinal Associates
state: Florida
city: Lexington
country: United States
facility: Shriners UK Ophthalmology - University of Kentucky
state: Kentucky
city: Portland
country: United States
facility: Casey Eye Institute, OHSU
state: Oregon
city: Dallas
country: United States
facility: Retina Foundation of the Southwest
state: Texas
Study officials:
affiliation: ProQR Therapeutics
name: ProQR Medical Monitor
role: STUDY_DIRECTOR
affiliation: ProQR Therapeutics
name: ProQR Clinical Trial Manager
role: STUDY_DIRECTOR
References: