E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Leber Congenital Amaurosis 10 (LCA10) 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 |
LCA10 due to a specific mutation in the CEP290 gene called c.2991+1655A>G or p.Cys998X |
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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 safety and tolerability of sepofarsen in pediatric subjects aged 3 to <8 years |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are to evaluate the effect of sepofarsen on structural and functional ophthalmic outcome measures. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female child, 3 to <8 years of age at Screening 2. A clinical diagnosis of LCA and a molecular diagnosis of homozygosity or compound heterozygosity for the c.2991+1655A>G mutation in the CEP290 gene, based on genotyping analysis at Screening. Historic genotyping results from a certified laboratory are acceptable with Sponsor approval. 3. Best corrected visual acuity (BCVA) equal to or better than Light Perception, and equal to or worse than approximate Snellen equivalent 20/50 in the treatment eye. 4. Clear ocular media and adequate pupillary dilation to permit good quality retinal imaging, as determined by the Investigator. |
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E.4 | Principal exclusion criteria |
1. Presence of additional homozygous or compound heterozygous pathogenic mutations (other than the c.2991+1655A>G mutation in the CEP290 gene) in genes associated with other recessive inherited retinal degenerative diseases or syndromes (eg, Usher syndrome) based on genotyping analysis. 2. Presence of any significant ocular or non-ocular disease/disorder (including medication abnormalities) which may either put the subject at risk because of participation in the trial, may influence the results of the trial, or the subject’s ability to participate in the trial. 3. Receipt within 3 months prior to Screening of any intraocular or periocular surgery (including refractive surgery), or an intravitreal (IVT) injection or planned intraocular surgery or procedure during the course of the trial. 4. Current treatment or treatment within the past 3 months or planned treatment with drugs known to be toxic to the lens, retina, or the optic nerve. 5. Use of any investigational drug or device within 3 months or 5 half-lives of Day 1, whichever is longer, or plans to participate in another study of a drug or device during the trial period. 6. Any prior receipt of genetic or stem-cell therapy for ocular or non-ocular disease.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoints are: • Incidence and severity of ocular AEs • Incidence and severity of non-ocular AEs |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Until 24 months after IVT injection |
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E.5.2 | Secondary end point(s) |
Secondary endpoints are: • Best-corrected visual acuity (BCVA) • Retinal sensitivity measured by Full-field stimulus testing (FST) (white, red, and blue)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
12 months Change from baseline values for these endpoints will also be assessed at other time points. |
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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 | No |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
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 | No |
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 | 3 |
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 |
European Union |
United Kingdom |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |