Leber’s Congenital Amaurosis (LCA) due to c.2991+1655A>G Mutation (p.Cys998X) in the CEP290 Gene MedDRA version: 20.0 Level: PT Classification code 10070667 Term: Leber's congenital amaurosis System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: QR-110
Product Code: QR-110
Pharmaceutical Form: Concentrate and solvent for solution for injection
INN or Proposed INN: Unavailable
CAS Number: 2227173-68-2
Current Sponsor code: QR-110
Sponsors
ProQR Therapeutics
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Male or female, = 8 years of age at Screening with a clinical diagnosis of LCA and a molecular diagnosis of homozygosity or compound heterozygosity for the CEP290 p.Cys998X mutation, based on genotyping analysis at Screening. Historic genotyping results from a certified laboratory are acceptable with Sponsor approval. 2.Detectable outer nuclear layer (ONL) in the area of the macula as determined by the reading center at Screening. 3.An ERG result consistent with LCA, as determined by the reading center. A historic ERG result may be acceptable for eligibility 4.Clear ocular media and adequate pupillary dilation to permit good quality retinal imaging, as assessed by the Investigator. Are the trial subjects under 18? yes Number of subjects for this age range: 13 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 17 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Any contraindication to IVT injection according to the Investigator’s clinical judgment and international guidelines (Avery 2014) 2.Any ocular and/or general disease or condition that could compromise subject’s safety or interfere with assessment of efficacy and safety, as determined by the Investigator 3.Prior receipt of intraocular surgery or IVT injection within 3 months prior to study start or planned intraocular surgery or procedure during the course of the study 4.Use of any investigational drug or device within 90 days or 5 half-lives of Day 1, whichever is longer, or plans to participate in another study of a drug or device during the PQ 110-003 study period 5.Any prior receipt of genetic therapy for LCA
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate the efficacy of QR-110 administered by intravitreal (IVT) injection in subjects with LCA due to the CEP290 p.Cys998X mutation ;Secondary Objective: The secondary objectives are to evaluate: - The safety and tolerability of QR-110 administered via IVT injection in subjects with LCA due to the CEP290 p.Cys998X mutation - Changes in quality of life in subjects with LCA due to the CEP290 p.Cys998X mutation treated with QR-110 - The systemic exposure of QR-110 administered by IVT injection in subjects with LCA due to the CEP290 p.Cys998X mutation ;Primary end point(s): The primary endpoint is mean change in BCVA relative to baseline versus sham;Timepoint(s) of evaluation of this end point: 12 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints are: - Percentage of subjects with baseline BCVA = 1.7 LogMAR with = -0.3 LogMAR change in BCVA in treated versus sham - Percentage of subjects with baseline BCVA < 1.7 LogMAR with a clinically meaningful improvement in mobility course score in treated versus sham - Change in BCVA relative to baseline in the dose level 1 group versus the dose level 2 group - Change in BCVA in both QR 110 dose groups pooled relative to baseline - Change in mobility course score relative to baseline in the treatment eye versus sham - Change in mobility course score binocular vision versus baseline versus sham - Change in oculomotor instability in treatment eye versus sham - Change in light sensitivity to white FST versus sham - Change in light sensitivity to red FST versus sham - Change in light sensitivity to blue FST versus sham - Change in photoreceptor inner segment/outer segment (inner segment [IS]/outer segment [OS]; ellipsoid zone [EZ] line) assessed by OCT relative to baseline - Change in patient reported visual function, as measured by the VFQ-25 score (adult subjects) relative to baseline - Change in patient reported visual function, as measured by the CVAQC (pediatric subjects) relative to baseline - Change in the patient-reported outcome (PRO) Patient Global Impressions of Severity (PGI S) - Change in the PRO Patient Global Impressions of Change (PGI C) - Systemic exposure of QR 110 - Change in ERG (International Society for Clinical Electrophysiology of Vision [ISCEV] standard for full-field clinical ERG) relative to baseline ;Timepoint(s) of evaluation of this end point: 24 months | — |
Countries
Belgium, Canada, European Union, France, Germany, Netherlands, United Kingdom, United States
Contacts
Public ContactClinical Trial Manager
ProQR Therapeutics
Outcome results
None listed