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)

ProQR Therapeutics

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Eye Diseases, Hereditary; Vision Tunnel; Vision Disorders; Retinal Dystrophies; Retinitis; Retinal Disease; Eye Diseases; Autosomal Dominant Retinitis Pigmentosa

Treatments: Drug: QR-1123; Other: Sham procedure

Study type: Interventional

Funder types: Industry

Identifiers

NCT04123626

PQ-1123-001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 11 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Triple Blind

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11 participants in 6 patient groups

QR-1123 Single dose - dose level 1

Experimental group

Description:

Open label Single dose cohort: dose level 1

Treatment:

Drug: QR-1123

QR-1123 Single dose - dose level 2

Experimental group

Description:

Open label Single dose cohort: dose level

Treatment:

Drug: QR-1123

QR-1123 Single dose - dose level 3

Experimental group

Description:

Open label Single dose cohort: dose level 3

Treatment:

Drug: QR-1123

QR-1123 Single dose - dose level 4

Experimental group

Description:

Open label Single dose cohort: dose level 4

Treatment:

Drug: QR-1123

QR-1123 Single dose - dose level 5

Experimental group

Description:

Open label Single dose cohort: dose level 5

Treatment:

Drug: QR-1123

Repeat dose cohort 1

Experimental group

Description:

Double-masked, randomized, sham controlled, Repeat dose cohort. Dose levels will be determined following DMC review of obtained safety and efficacy data.

Treatment:

Other: Sham procedure

Drug: QR-1123