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: Sepofarsen
CAS Number: 2227173-68-2
Current Sponsor code: QR-110
Sponsors
ProQR Therapeutics IV B.V.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Relating to Study Initiation : The subject is eligible for the study and thus eligible to receive QR-110 or sham-procedure in the treatment eye (ie, the first eye to be treated) if all the following inclusion criteria apply at Screening/Day 1: 1. An adult (= 18 years) willing and able to provide informed consent for participation -OR- a minor (8 to G mutation, based on genotyping analysis at Screening. A historic genotyping report from a certified laboratory is acceptable with Sponsor approval. 3. BCVA better or equal to Logarithm of the Minimum Angle of Resolution (logMAR) +3.0 (Hand Motion), and equal or worse than logMAR + 0.4 (approximate Snellen equivalent 20/50) in the treatment eye, using the best BCVA reading at Screening and based on the Early Treatment Diabetic Retinopathy Study (ETDRS) or the Berkeley rudimentary vision test (BRVT). 4. Detectable outer nuclear layer (ONL) in the area of the macula as determined by the Investigator at Screening. 5. An electroretinogram (ERG) result consistent with LCA, as determined by the Investigator. A historic ERG result may be acceptable for eligibility. 6. Clear ocular media and adequate pupillary dilation to permit good quality retinal imaging, as assessed by the Investigator. 7. Non-pregnant and non-breastfeeding subjects. Relating to Treatment Initiation Contralateral Eye: 1. BCVA better or equal to Logarithm of the Minimum Angle of Resolution (logMAR) +3.0 (Hand Motion), and equal or worse than logMAR + 0.4 (approximate Snellen equivalent 20/50) in the contralateral eye, using the best BCVA reading at Month 12 (see Section 8.1) and based on the Early Treatment Diabetic Retinopathy Study (ETDRS) or the Berkeley Rudimentary Vision Test (BRVT). 2. Detectable outer nuclear layer (ONL) in the area of the macula of the contralateral eye as determined by the Investigator. 3. Clear ocular media and adequate pupillary dilation to permit good quality retinal imaging in the contralateral eye, as assessed by the Investigator. 4. Non-pregnant and non-breastfeeding subjects. Are the trial subjects under 18? yes Number of subjects for this age range: 11 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 25 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Relating to Study Initiation : The subject is ineligible for the study if any of the following criteria apply at Screening/Day 1: 1. 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. 2. 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 study period. 3. Any prior receipt of genetic or stem-cell therapy for ocular or non-ocular disease. 4. Receipt within 1 month prior to Screening of any intraocular or periocular surgery (including refractive surgery), or an IVT injection or planned intraocular surgery or procedure during the course of the study. Subjects who received an intraocular or periocular surgery between 1 to 3 months prior Screening, may only be considered for inclusion if there are no clinically significant complications of surgery present, and following approval by the Medical Monitor. 5. Known hypersensitivity to antisense oligonucleotides or any constituents of the injection. 6. Pregnant and breastfeeding subjects. Relating to Treatment Initiation Contralateral Eye: 1. 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. This includes but is not limited a subject who: 1) is not an appropriate candidate for antisense oligonucleotide treatment, 2) has concurrent cystoid macular edema (CME) in the contralateral eye. 2. A planned IVT injection or intraocular or periocular surgery/procedure (including refractive surgery) in the contralateral eye during the course of the study. 3. Plans to participate in another study of a drug or device during the study period. 4. Pregnant and breastfeeding subjects.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): The primary endpoint is change from baseline in BCVA (based on ETDRS and/or BRVT) at 12 months of treatment versus sham-procedure;Timepoint(s) of evaluation of this end point: 12 months;Main Objective: The primary objective is to evaluate the efficacy of QR-110 administered by intravitreal (IVT) injection ;Secondary Objective: The secondary objectives are to evaluate: - The safety and tolerability of QR-110 administered via IVT injection - Changes in patient-reported outcome (PRO) measures in subjects treated with QR-110 - The systemic exposure of QR-110 administered via IVT injection | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Change from baseline in mobility course score at 12 months of treatment versus sham, as assessed by a masked central reader Secondary endpoints : • Change from baseline in BCVA: o By = 3 lines (or = -0.3 logMAR change) in subjects with BCVA better than 1.7 logMAR at baseline o By a clinically meaningful improvement in subjects with BCVA equal to worse than 1.7 logMAR at baseline • Change from baseline in mobility course score • Change from baseline in BCVA based on Freiburg visual acuity and contrast Test (FrACT) • Change from baseline in light sensitivity to FST (white, red, and blue) • Change from baseline in ellipsoid zone (EZ) width/area assessed by spectral domain optical coherence tomography SD-OCT • Change from baseline in low luminance visual acuity (LLVA) • Change from baseline in oculomotor instability (OCI) • Change from baseline as determined by fundus autofluorescence (FAF) imaging • Change from baseline as determined by microperimetry • Change from baseline in PRO measures, as measured by: o The Visual Function Questionnaire-25 (VFQ-25) score (adult subjects) o The Cardiff Visual Ability Questionnaire for Children (CVAQC) (pediatric subjects) o the Patient Global Impressions of Severity (PGI S) o the Patient Global Impressions of Change (PGI C) • Systemic exposure to QR-110 • Ocular and non-ocular adverse events (AEs);Timepoint(s) of evaluation of this end point: 24 months | — |
Countries
Belgium, Brazil, Canada, European Union, France, Germany, Italy, Netherlands, United Kingdom, United States
Contacts
Public ContactClinical Trial Manager
ProQR Therapeutics IV B.V.
Outcome results
None listed