E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Leber’s 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 | 19.1 |
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 the 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 the pharmacokinetics of QR-110
• to evaluate the efficacy of QR-110
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female, ≥ 6 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.
2. Best-corrected visual acuity greater than or equal to light perception in both eyes and equal to or worse than LogMAR + 1.0 (Snellen notation 20/200) in the worse eye and equal to or worse than LogMAR + 0.7 (Snellen notation 20/100) in the contralateral eye.
3. Detectable outer nuclear layer (ONL) in the area of the macula.
4. An ERG result consistent with LCA.
5. Clear ocular media and adequate pupillary dilation to permit good quality retinal imaging |
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E.4 | Principal exclusion criteria |
1. Syndromic disease
2. Pregnant or breast-feeding female
3. Any clinically significant cardiac disease or defect.
4. One or more coagulation parameters outside of the normal range.
5. Any ocular disease or condition that could compromise treatment safety, visual acuity or interfere with assessment of efficacy and safety.
6.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
7. 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-110-001 study period.
8. Any prior receipt of genetic therapy for LCA |
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E.5 End points |
E.5.1 | Primary end point(s) |
Frequency and severity of ocular AEs in the treatment and contralateral eyes |
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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) |
Frequency and severity of non-ocular AEs
Changes in ophthalmic examination findings
Change in BCVA
Changes in infrared imaging
Changes in OCT findings
Changes in safety parameters, including vital sign measurements, physical examination findings, ECG, and laboratory parameters
Characterize the PK profile of QR-110 in serum
Change in light sensitivity by FST
Change in cone mediated light sensitivity by FST
Change in rod mediated light sensitivity by FST
Change in PLR amplitude
Change in PLR latency
Change in melanopsin-mediated PLR
Change in cone-mediated PLR end
Change in rod-mediated PLR
Change in mobility course score
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Frequency and severity of non-ocular AEs – All 21 visits
Changes in ophthalmic examination findings – All 21 visits
Change in BCVA – Visits 1, 2, 6, 7, 8, 11, 12, 13, 16, 17, 20, 21
Changes in infrared imaging and OCT findings - Visits 1, 6, 7, 8, 11, 12, 13, 16, 17, 20, 21
Changes in safety parameters – Throughout the 21 visits
Characterize the PK profile of QR-110 in serum – Visits 2, 3, 4, 6, 7, 8, 10, 13, 17
Changes measured by FST, by PLR and in mobility course score – Visits 1, 2, 6, 7, 8, 13, 17, 21
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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 | No |
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) | Yes |
E.7.1.1 | First administration to humans | Yes |
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 | 6 |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 18 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 18 |
E.8.9.2 | In all countries concerned by the trial days | 0 |