E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Retinitis Pigmentosa (RP) due to Mutations in Exon 13 of the USH2A Gene |
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E.1.1.1 | Medical condition in easily understood language |
RP due to Mutations in Exon 13 of the USH2A Gene |
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E.1.1.2 | Therapeutic area | Diseases [C] - Eye Diseases [C11] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10038914 |
E.1.2 | Term | Retinitis pigmentosa |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of QR-421a |
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E.2.2 | Secondary objectives of the trial |
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 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 (16 to <18 years) 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.
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E.4 | Principal 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
Mean 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 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At multiple timepoints up to 18 months |
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E.5.2 | Secondary end point(s) |
Key Secondary endpoints Proportion of patients who maintain vision defined by BCVA loss less than 15 Letters (based on ETDRS)
Other Secondary endpoints Change from baseline in the following outcome measures: Other analyses 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 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At multiple timepoints up to 24 months |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Brazil |
Canada |
United States |
European Union |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |