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 safety and tolerability of QR-421a. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the serum pharmacokinetics (PK) of QR-421a. To evaluate the efficacy of QR-421a, as assessed by functional and structural outcome measures. To evaluate the dose-response and duration of structural and functional effects of a single dose of QR-421a.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
To evaluate the effect of QR-421a on subject mobility with a Streetlab course. |
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E.3 | Principal inclusion criteria |
• Male or female, ≥ 18 years of age. • Clinical presentation consistent with RP with Usher syndrome type 2 or NSRP, based on ophthalmic, audiologic, and vestibular examinations. • An ERG result consistent with RP with Usher syndrome type 2 or NSRP. • A molecular diagnosis of homozygosity or compound heterozygosity for 1 or more pathogenic exon 13 mutations in the USH2A gene, based on genetic analysis upon Sponsor approval. • No limitations to OCT image collection that would prevent high quality, reliable images from being obtained in both eyes (including outer segment [OS] thickness and volume, outer nuclear layer [ONL] thickness, total receptor (TR) thickness, EZ horizontal and vertical widths, apparent continuous EZ area, central macula thickness [CMT], grading of cystic macular lesions [CML] if any), as determined by the reading center. • Reliable perimetry measurements in both eyes, as described in the Study Reference Manual and determined by the reading center. • Clear ocular media and adequate pupillary dilation to permit good quality retinal imaging, as assessed by the Investigator. |
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E.4 | Principal exclusion criteria |
• Presence of additional non-exon 13 USH2A pathogenic mutation(s) on the USH2A allele carrying the exon 13 mutation in subjects who are compound heterozygous for mutations in exon 13. • Presence of non-exon 13 USH2A pathogenic mutation(s) on both USH2A alleles in subjects who are homozygous for mutations in exon 13. • Presence of pathogenic mutations in genes (other than the USH2A gene) associated with Usher syndrome Type 2 or NSRP, or other inherited retinal degenerative diseases or syndromes. • Any contraindication to IVT injection according to the Investigator’s clinical judgment and international guidelines. • Nystagmus or unstable fixation. • Amblyopia. • Prior receipt of intraocular surgery or procedure or IVT injection within 12 weeks prior to study start or planned intraocular surgery or procedure during the course of the study. • Any prior treatment with genetic therapy. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Frequency and severity of ocular adverse events (AEs) in the treatment and contralateral eye. • Frequency and severity of non-ocular AEs.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At multiple timepoints up to 12 months. |
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E.5.2 | Secondary end point(s) |
• PK profile of QR-421a in serum. • Change in Dark Adapted Chromatic (DAC) VF. • Change in static VF. • Change in Ellipsoid Zone (EZ) area by optical coherence tomography (OCT). • Change in Best Corrected Visual Acuity (BCVA). • Change in semi-kinetic VF. • Change in microperimetry. • Changes in ERG ((International Society for Clinical Electrophysiology of Vision [ISCEV] standard for full-field clinical ERG). • Changes in near-infrared autofluorescence (NIRAF). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At multiple timepoints up to 12 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 | 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 | 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 | 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 |
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E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 2 |
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 |
Belgium |
Canada |
France |
United States |
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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 | 22 |
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 | 22 |
E.8.9.2 | In all countries concerned by the trial days | 0 |