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

Eye Diseases Clinical Trial

— AURORA  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04123626
• Other study ID #: PQ-1123-001
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: October 7, 2019
• Est. completion date: June 7, 2022

Study information

• Verified date: May 2022
• Source: ProQR Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 11
• Est. completion date: June 7, 2022
• Est. primary completion date: June 7, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Arthrogryposis
• Autosomal Dominant Retinitis Pigmentosa
• Eye Diseases
• Eye Diseases, Hereditary
• Genetic Diseases, Inborn
• Retinal Disease
• Retinal Diseases
• Retinal Dystrophies
• Retinitis
• Retinitis Pigmentosa
• Vision Disorders
• Vision Tunnel

Intervention

Drug:
• QR-1123
unilateral IVT injection

Other:
• Sham procedure
Sham procedures (i.e. no penetration of the globe) closely mimic the active injection and serve to mask subjects to treatment assignment

Locations

Country	Name	City	State
United States	Sue Anschutz-Rogers Eye Center, University of Colorado - Dept. of Ophthalmology	Aurora	Colorado
United States	Retina Foundation of the Southwest	Dallas	Texas
United States	VitreoRetinal Associates	Gainesville	Florida
United States	Shriners UK Ophthalmology - University of Kentucky	Lexington	Kentucky
United States	Casey Eye Institute, OHSU	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
ProQR Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and Severity of ocular AEs	Incidence and severity of ocular adverse events scored based on CTCAC in the study and fellow eye	up to 12 months
Primary	Incidence and Severity of non-ocular AEs	Incidence and severity of non-ocular adverse events scored based on CTCAC in the study and fellow eye	up to 12 months
Secondary	Changes in BCVA	Changes in Best corrected visual acuity (BCVA)	up to 12 months
Secondary	Changes in LLVA	Changes in Low-luminance visual acuity (LLVA)	up to 12 months
Secondary	Changes in DAC perimetry	Changes in Dark adapted chromatic (DAC) perimetry	up to 12 months
Secondary	Changes in Static VF	Changes in Static VF (Visual Field)	up to 12 months
Secondary	Changes in Microperimetry	Changes in Microperimetry	up to 12 months
Secondary	Changes in SD-OCT	Changes in Spectral Domain-Optical Coherence Tomography	up to 12 months
Secondary	Changes in FST	Changes in Full-field Stimulus Threshold (FST)	up to 12 months
Secondary	Changes in Full-field ERG	Changes in Full-field Electroretinogram (ERG)	up to 12 months
Secondary	Assessment of systemic exposure after treatment with QR-1123	Serum levels of QR-1123	up to 12 months