E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Achromatopsia caused by mutations in the CNGA3 gene |
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E.1.1.1 | Medical condition in easily understood language |
Impairment of colour vision and visual acuity caused by mutations in the CNGA3 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 | LLT |
E.1.2 | Classification code | 10000454 |
E.1.2 | Term | Achromatopsia |
E.1.2 | System Organ Class | 100000004850 |
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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 safety of a AAV2/8 vector for hCNGA gene replacement in the retina. Safety is defined as the absence of ATIMP-related event including, reduction in visual acuity by 15 ETDRS letters, Severe unresponsive inflammation, Infective endophthalmitis, Ocular malignancy, Grade III or above non-ocular SUSAR |
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E.2.2 | Secondary objectives of the trial |
The secondary research objective is to determine whether an AAV2/8 vector for hCNGA3 gene replacement in the retina can improve retinal function, visual function and quality of life. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Key Inclusion Criteria: • Aged 3 to 15 years old • Achromatopsia caused by mutations in CNGA3 • Evidence of preservation of photoreceptors at the macula • Able to undertake age-appropriate clinical assessments • Willing to give consent for the use of blood and blood components collected throughout the trial for the investigation of immune response to Advanced Therapy Investigational Product (ATIMP). |
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E.4 | Principal exclusion criteria |
Key Exclusion Criteria: • Female adolescents who are pregnant or breastfeeding • Intra-ocular surgery within 6 months of screening Ocular or systemic disorder that may preclude subretinal surgery and/or interfere with interpretation of the study results. • Participated in another research study involving an investigational therapy for ocular disease within the last 6 months • Have any other condition that the Principal Investigator (PI) considers makes them inappropriate for entry into the trial • Are unwilling to consider the possibility of entry into a subsequent longer term follow up study |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome is safety of subretinal administration of AAV2/8-hG1.7p.cohCNGA3.
Safety is defined as the absence of ATIMP-related: • Reduction in visual acuity by 15 ETDRS letters or more that fails to resolve to within 15 letters of baseline in a 4 week period once prophylactic treatment commences • Severe unresponsive inflammation • Infective endophthalmitis • Ocular malignancy • Grade III or above non-ocular SUSAR
Safety will be assessed for 6 months after the intervention in this study, and a further 4.5 years in a separate subsequent study. |
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E.5.2 | Secondary end point(s) |
The secondary outcomes are measures of the efficacy of the intervention, which will be performed on an individual participant basis and will be descriptive in nature. Efficacy will be assessed at several time points between 3 to 6 months after the intervention:
1) Any improvement in visual function from baseline that is greater than the baseline variation for that test and is sustained for at least two consecutive assessments. 2) Any improvement in retinal function from pre-intervention that is greater than the baseline variation and measurable by electroretinography (ERG). 3) Quality of life measures including EQ-5D and IVI or equivalent as appropriate. |
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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 | No |
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 | 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.8.3 |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 31 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 31 |