E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Leber Congenital Amaurosis (LCA) caused by mutations in RPE65 |
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E.1.1.1 | Medical condition in easily understood language |
Retinal degeneration caused by mutations in RPE65 |
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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 research objective is to assess the longer term safety of AAV2/5-OPTIRPE65 administered to participants in the OPTIRPE65 trial, measured by the presence or absence of adverse events, the assessment of visual acuity, and loss of light perception. |
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E.2.2 | Secondary objectives of the trial |
The secondary research objective is to explore the longer term efficacy of AAV2/5-OPTIRPE65 in improving visual and retinal function, and quality of life, and protecting against sight impairment from retinal degeneration. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion in the study will be limited to individuals who meet the following criteria: • Are able to give informed consent or assent, with or without the guidance of their parent/guardian where appropriate • Were enrolled and treated in the prior open-label, Phase I/II, dose escalation study involving singular intraocular administration of AAV2/5-0PTIRPE65 • The contralateral eye may be untreated or treated with Voretigene Neparvovec. • Are willing to adhere to the protocol and long-term follow-up |
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E.4 | Principal exclusion criteria |
Individuals will be excluded if they are unwilling or unable to meet with the requirements of the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary study outcome is the safety of the subretinal administration of AAV2/5-OPTIRPE65. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At 9, 12, 18, 24, 36, 48 and 60 months after AAV2/5-OPTIRPE65 administration |
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E.5.2 | Secondary end point(s) |
The secondary outcomes are measures of the efficacy of AAV2/5-OPTIRPE65: 1) Any improvements in visual function from baseline that are greater than the test-retest variation and are sustained for at least two consecutive assessments. 2) Quality of life will be measured by the Impact of Visual Impairment (IVI) questionnaire and the EQ5D-5L and EQ-5D-Y. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At 9, 12, 18, 24, 36, 48 and 60 months after AAV2/5-OPTIRPE65 administration |
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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 | No |
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 | No |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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.8.3 |
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 |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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 | 7 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |