A Phase 2/3 study to evaluate efficacy, safety, and tolerability of QR-421a in subjects with advanced vision loss

Phase 1

Conditions: Retinitis Pigmentosa (RP) due to Mutations in Exon 13 of the USH2A Gene
MedDRA version: 20.0Level: PTClassification code 10038914Term: Retinitis pigmentosaSystem Organ Class: 10010331 - Congenital, familial and genetic disorders
Therapeutic area: Diseases [C] - Eye Diseases [C11]

Registration Number: EUCTR2021-002729-74-NO

Lead Sponsor: ProQR Therapeutics IV B.V.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: A

Sex: All

Target Recruitment: 81

Inclusion Criteria

- An adult (= 18 years) willing and able to provide informed consent for participation prior to performing any study related procedure. OR A minor able to complete all study assessments and comply with the protocol and has a parent or caregiver willing and able to follow study instructions, and attend study visits with the subject as required.
- Clinical presentation consistent with RP with Usher syndrome type 2 or non-syndromic form of RP (NSRP), based on ophthalmic, audiologic, and vestibular examinations.
- A molecular diagnosis of homozygosity or compound heterozygosity for 1 or more pathogenic exon 13 mutations in the USH2A gene, based on genetic analysis at screening.
- Reliable BCVA, perimetry, and other measurements in both eyes.

Are the trial subjects under 18? yes
Number of subjects for this age range: 5
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 74
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2

Exclusion Criteria

- Presence of any significant ocular or non-ocular disease/disorder (or medication and/or 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.
- Known hypersensitivity to antisense oligonucleotides or any constituents of the injection.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of QR-421a;Secondary Objective: To evaluate the safety and tolerability of QR-421a<br>To evaluate changes in Patient-Reported Outcome (PRO) measures in subjects treated with QR-421a<br>To evaluate systemic exposure of QR-421a;Primary end point(s): Change from baseline in best corrected visual acuity (BCVA) (based on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart) at 18 months of treatment versus sham-procedure;Timepoint(s) of evaluation of this end point: At multiple timepoints up to 18 months

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Change from baseline in the following outcome measures:<br> Other measures of BCVA<br> Spectral domain optical coherence tomography (SD-OCT)<br> Low Luminance Visual Acuity (LLVA)<br> Microperimetry<br> Static perimetry<br> Full-field Stimulus Threshold (FST)<br>Change from baseline in PRO measures, as assessed by:<br> Veteran Administration Low Vision Visual Functioning Questionnaire (VA LV VFQ-20) (Stelmack 2007)<br> Patient Global Impressions of Severity (PGI-S)<br> Patient Global Impressions of Change (PGI-C)<br>Ocular and non-ocular adverse events (AEs) Exposure of QR-421a in serum;Timepoint(s) of evaluation of this end point: At multiple timepoints up to 24 months

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