E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Leber Congenital Amaurosis (LCA) due to c.2991+1655A>G Mutation (p.Cys998X) in the CEP290 Gene |
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E.1.1.1 | Medical condition in easily understood language |
LCA due to the p.Cys998X mutation in the CEP290 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 | 10070667 |
E.1.2 | Term | Leber's congenital amaurosis |
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 |
The primary objective of the study is to evaluate long term safety and tolerability of QR-110 administered via IVT injection in subjects with LCA due to the CEP290 p.Cys998X mutation. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are: * to evaluate long-term and sustained efficacy of QR-110 administered by IVT injection, as assessed by functional and structural outcome measures * to evaluate changes in Patient Reported Outcome (PROs) measures in subjects treated with QR-110 * to evaluate long-term serum pharmacokinetics of QR-110 administered by IVT injection
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Subjects who completed participation in the study PQ-110-001 and who may derive benefit from continued treatment with QR-110, as assessed by the Investigator, in consultation with the Medical Monitor 2.Persistence of detectable outer nuclear layer (ONL) in the area of the macula in the opinion of the Investigator, as determined by OCT. 3.Clear ocular media and adequate pupillary dilation to permit good quality retinal imaging, as assessed by the Investigator. 4.An adult (≥ 18 years) willing and able to provide informed consent for participation OR a minor (6 to < 18 years) with a parent or legal guardian willing and able to provide written permission for the subject’s participation prior to performing any study related procedures, and pediatric subjects able to provide age-appropriate assent for study participation.
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E.4 | Principal exclusion criteria |
1.Any contraindication to IVT injection according to the Investigator’s clinical judgment and international guidelines (Avery 2014). 2.Any ocular or systemic disease or condition (including medications and laboratory test abnormalities) that could compromise subject safety or interfere with assessment of efficacy and safety, as determined by the Investigator.
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E.5 End points |
E.5.1 | Primary end point(s) |
- Frequency and severity of - ocular adverse events (AEs) - Frequency and severity of non-ocular AEs |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
* Change from Baseline in BCVA * Change from Baseline in Mobility course score (unilateral and binocular) * Change from Baseline in photoreceptor outer segment layer thickness by optical coherence tomography (OCT) (if applicable) * Change in OCI * Change in Full-FST (blue and red stimuli; white at Investigator discretion) (thresholds) * Change from Baseline in Patient Reported Outcomes * Change in Pupillary Light Reflex (PLR) (latency and amplitude) * Change in Near Infrared AutoFluorescence (NIRAF) * Pharmacokinetics: Characterize the PK profile of QR-110 in serum |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
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 |
The contralateral eye and the subject’s own baseline measurements will serve as controls |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | No |
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 |
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |