Study to evaluate QR-421a in subjects with retinitis pigmentosa (RP) due to mutations in exon 13 of the USH2A Gene

Phase 1

• Conditions: 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]

• Registration Number: EUCTR2018-002433-38-FR
• Lead Sponsor: ProQR Therapeutics

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-11-16
• Last Update Posted: 30 April 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 18

Inclusion Criteria

• Male or female, = 18 years of age.
• Clinical presentation consistent with RP with Usher syndrome type 2 or NSRP, based on ophthalmic, audiologic, and vestibular examinations.
• An ERG result consistent with RP with Usher syndrome type 2 or NSRP.
• A molecular diagnosis of homozygosity or compound heterozygosity for 1 or more pathogenic exon 13 mutations in the USH2A gene, based on genetic analysis upon Sponsor approval.
• No limitations to OCT image collection that would prevent high quality, reliable images from being obtained in both eyes (including outer segment [OS] thickness and volume, outer nuclear layer [ONL] thickness, total receptor (TR) thickness, EZ horizontal and vertical widths, apparent continuous EZ area, central macula thickness [CMT], grading of cystic macular lesions [CML] if any), as determined by the reading center.
• Reliable perimetry measurements in both eyes, as described in the Study Reference Manual and determined by the reading center.
• Clear ocular media and adequate pupillary dilation to permit good quality retinal imaging, as assessed by the Investigator.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 16
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 2

Exclusion Criteria

• Presence of additional non-exon 13 USH2A pathogenic mutation(s) on the USH2A allele carrying the exon 13 mutation in subjects who are compound heterozygous for mutations in exon 13.
• Presence of non-exon 13 USH2A pathogenic mutation(s) on both USH2A alleles in subjects who are homozygous for mutations in exon 13.
• Presence of pathogenic mutations in genes (other than the USH2A gene) associated with Usher syndrome Type 2 or NSRP, or other inherited retinal degenerative diseases or syndromes.
• Any contraindication to IVT injection according to the Investigator’s clinical judgment and international guidelines.
• Nystagmus or unstable fixation.
• Amblyopia.
• Prior receipt of intraocular surgery or procedure or IVT injection within 12 weeks prior to study start or planned intraocular surgery or procedure during the course of the study.
• Any prior treatment with genetic therapy.

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 safety and tolerability of QR-421a.;<br> Secondary Objective: To evaluate the serum pharmacokinetics (PK) of QR-421a.<br> To evaluate the efficacy of QR-421a, as assessed by functional and structural outcome measures.<br> To evaluate the dose-response and duration of structural and functional effects of a single dose of QR-421a.<br><br> ;<br> Primary end point(s): • Frequency and severity of ocular adverse events (AEs) in the treatment and contralateral eye.<br> • Frequency and severity of non-ocular AEs.<br> ;Timepoint(s) of evaluation of this end point: At multiple timepoints up to 12 months.

Secondary Outcome Measures

Name	Time	Method
<br> Secondary end point(s): • PK profile of QR-421a in serum.<br> • Change in Dark Adapted Chromatic (DAC) VF.<br> • Change in static VF.<br> • Change in Ellipsoid Zone (EZ) area by optical coherence tomography (OCT).<br> • Change in Best Corrected Visual Acuity (BCVA).<br> • Change in semi-kinetic VF.<br> • Change in microperimetry.<br> • Changes in ERG ((International Society for Clinical Electrophysiology of Vision [ISCEV] standard for full-field clinical ERG).<br> • Changes in near-infrared autofluorescence (NIRAF).<br> ;Timepoint(s) of evaluation of this end point: At multiple timepoints up to 12 months.