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

• Register: EUCTR
• Last refreshed on: 17 January 2022
• Main ID: EUCTR2021-002729-74-NL
• Date of registration: 15/01/2022
• Prospective Registration: Yes
• Primary sponsor: ProQR Therapeutics IV B.V.
• Public title: A Phase 2/3 study to evaluate efficacy, safety, and tolerability of QR-421a in subjects with advanced vision loss
• Scientific title: A Double-Masked, Randomized, Controlled, Multiple-Dose Study to Evaluate the Efficacy, Safety and Tolerability of QR-421a in Subjects with Retinitis Pigmentosa (RP) due to Mutations in Exon 13 of the USH2A Gene with Advanced Vision Loss - Sirius
• Target sample size: 81
• Recruitment status: NA
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2021-002729-74
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: yes; Other trial design description: Multiple-Dose Study; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: yes; Other specify the comparator: Sham; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Brazil, Canada, European Union, Germany, Netherlands, Norway, United Kingdom, United States

Contacts

• Name: Clinical Trial Manager
• Affiliation: ProQR Therapeutics IV B.V.

• Name: Clinical Trial Manager
• Affiliation: ProQR Therapeutics IV B.V.

Key inclusion & exclusion criteria

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.




Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Retinitis Pigmentosa (RP) due to Mutations in Exon 13 of the USH2A Gene
MedDRA version: 20.0 Level: PT Classification code 10038914 Term: Retinitis pigmentosa System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Diseases [C] - Eye Diseases [C11]

Intervention(s)

Product Name: QR-421a
Product Code: QR-421a
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Not available
Current Sponsor code: QR-421a
Other descriptive name: QR-421a
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 15-

Primary Outcome(s)

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

Secondary Objective: To further evaluate efficacy
To evaluate the safety and tolerability of QR-421a
To evaluate changes in Patient-Reported Outcome (PRO) measures in subjects treated with QR-421a
To evaluate systemic exposure of QR-421a

Timepoint(s) of evaluation of this end point: At multiple timepoints up to 18 months

Main Objective: To evaluate the efficacy of QR-421a

Secondary Outcome(s)

Secondary end point(s): Key Secondary endpoints:

- Proportion of patients who maintain vision defined by BCVA loss less than 15 Letters (ETDRS)

Other Secondary endpoints:
- Change from baseline in the following outcome measures:
Other measures of BCVA
Spectral domain optical coherence tomography (SD-OCT)
Low Luminance Visual Acuity (LLVA)
Microperimetry
Static perimetry
Full-field Stimulus Threshold (FST)
Change from baseline in PRO measures, as assessed by:
Veteran Administration Low Vision Visual Functioning Questionnaire (VA LV VFQ-20) (Stelmack 2007)
Patient Global Impressions of Severity (PGI-S)
Patient Global Impressions of Change (PGI-C)
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

Secondary ID(s)

2021-002729-74-DE

PQ-421a-003

Source(s) of Monetary Support

ProQR Therapeutics IV B.V.