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 (AURORA)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Eye Diseases; Retinitis; Eye Diseases, Hereditary; Retinal Dystrophies; Vision Disorders; Retinal Disease; Autosomal Dominant Retinitis Pigmentosa; Vision Tunnel
• Intervention / Treatment: Drug: QR-1123; Other: Sham procedure

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.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Sue Anschutz-Rogers Eye Center, University of Colorado - Dept. of Ophthalmology
  • Florida
    • Gainesville, Florida, United States, 32607
      • VitreoRetinal Associates
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Shriners UK Ophthalmology - University of Kentucky
  • Oregon
    • Portland, Oregon, United States, 97239
      • Casey Eye Institute, OHSU
  • Texas
    • Dallas, Texas, United States, 75231
      • Retina Foundation of the Southwest

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: QR-1123 Single dose - dose level 1; Open label Single dose cohort: dose level 1	Drug: QR-1123; unilateral IVT injection
Experimental: QR-1123 Single dose - dose level 2; Open label Single dose cohort: dose level	Drug: QR-1123; unilateral IVT injection
Experimental: QR-1123 Single dose - dose level 3; Open label Single dose cohort: dose level 3	Drug: QR-1123; unilateral IVT injection
Experimental: QR-1123 Single dose - dose level 4; Open label Single dose cohort: dose level 4	Drug: QR-1123; unilateral IVT injection
Experimental: QR-1123 Single dose - dose level 5; Open label Single dose cohort: dose level 5	Drug: QR-1123; unilateral IVT injection
Experimental: 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.	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in BCVA	Changes in Best corrected visual acuity (BCVA)	up to 12 months
Changes in LLVA	Changes in Low-luminance visual acuity (LLVA)	up to 12 months
Changes in DAC perimetry	Changes in Dark adapted chromatic (DAC) perimetry	up to 12 months
Changes in Static VF	Changes in Static VF (Visual Field)	up to 12 months
Changes in Microperimetry	Changes in Microperimetry	up to 12 months
Changes in SD-OCT	Changes in Spectral Domain-Optical Coherence Tomography	up to 12 months
Changes in FST	Changes in Full-field Stimulus Threshold (FST)	up to 12 months
Changes in Full-field ERG	Changes in Full-field Electroretinogram (ERG)	up to 12 months
Assessment of systemic exposure after treatment with QR-1123	Serum levels of QR-1123	up to 12 months

Collaborators and Investigators

• Sponsor: ProQR Therapeutics
• Investigators: Study Director: ProQR Medical Monitor, ProQR Therapeutics; Study Director: ProQR Clinical Trial Manager, ProQR Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2019
• Primary Completion (Anticipated): June 7, 2022
• Study Completion (Anticipated): June 7, 2022

Study Registration Dates

• First Submitted: October 1, 2019
• First Submitted That Met QC Criteria: October 10, 2019
• First Posted (Actual): October 11, 2019

Study Record Updates

• Last Update Posted (Actual): May 6, 2022
• Last Update Submitted That Met QC Criteria: May 5, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Rhodopsin; Retinitis Pigmentosa; antisense oligonucleotide; IVT; adRP; P23H mutation; autosomal dominant
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Congenital Abnormalities; Retinal Degeneration; Joint Diseases; Musculoskeletal Diseases; Muscular Diseases; Sensation Disorders; Musculoskeletal Abnormalities; Retinal Diseases; Retinitis; Retinitis Pigmentosa; Eye Diseases; Genetic Diseases, Inborn; Vision Disorders; Arthrogryposis; Retinal Dystrophies; Eye Diseases, Hereditary
• Other Study ID Numbers: PQ-1123-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No