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

NCT04123626 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: PQ-1123-001
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 5

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.

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (9)

• Changes in BCVA

  up to 12 months

• Changes in LLVA

  up to 12 months

• Changes in DAC perimetry

  up to 12 months

• Changes in Static VF

  up to 12 months

• Changes in Microperimetry

  up to 12 months

Study Arms (6)

QR-1123 Single dose - dose level 1

EXPERIMENTAL

Open label Single dose cohort: dose level 1

Drug: QR-1123

QR-1123 Single dose - dose level 2

EXPERIMENTAL

Open label Single dose cohort: dose level

Drug: QR-1123

QR-1123 Single dose - dose level 3

EXPERIMENTAL

Open label Single dose cohort: dose level 3

Drug: QR-1123

QR-1123 Single dose - dose level 4

EXPERIMENTAL

Open label Single dose cohort: dose level 4

Drug: QR-1123

QR-1123 Single dose - dose level 5

EXPERIMENTAL

Open label Single dose cohort: dose level 5

Drug: QR-1123

Repeat dose cohort 1

EXPERIMENTAL

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; Other: Sham procedure

Interventions

QR-1123 DRUG

unilateral IVT injection

QR-1123 Single dose - dose level 1; QR-1123 Single dose - dose level 2; QR-1123 Single dose - dose level 3; QR-1123 Single dose - dose level 4; QR-1123 Single dose - dose level 5; Repeat dose cohort 1

Sham procedure OTHER

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

Repeat dose cohort 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• ProQR Therapeutics: lead

Study Sites (5)

Sue Anschutz-Rogers Eye Center, University of Colorado - Dept. of Ophthalmology

Aurora, Colorado, 80045, United States

Location

VitreoRetinal Associates

Gainesville, Florida, 32607, United States

Location

Shriners UK Ophthalmology - University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Casey Eye Institute, OHSU

Portland, Oregon, 97239, United States

Location

Retina Foundation of the Southwest

Dallas, Texas, 75231, United States

Location

MeSH Terms

Conditions

Eye Diseases; Eye Diseases, Hereditary; Retinal Dystrophies; Retinal Diseases; Retinitis; Vision Disorders; Retinitis Pigmentosa; Night Blindness, Congenital Stationary, Autosomal Dominant 1; Multiple Pterygium Syndrome, Autosomal Dominant

Condition Hierarchy (Ancestors)

Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Retinal Degeneration; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• ProQR Medical Monitor

  ProQR Therapeutics

  STUDY DIRECTOR

• ProQR Clinical Trial Manager

  ProQR Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Single dose cohorts are open label. Repeat dose cohorts are randomized, double masked.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2019
• First Posted: October 11, 2019
• Study Start: October 7, 2019
• Primary Completion: June 7, 2022
• Study Completion: June 7, 2022
• Last Updated: May 6, 2022

Record last verified: 2022-05

Locations

US (5)