E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10010331 |
E.1.2 | Term | Congenital, familial and genetic disorders |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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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 | 10011386 |
E.1.2 | Term | Crigler-Najjar syndrome |
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 characterize the safety and preliminary efficacy of AT342 in subjects with Crigler Najjar syndrome requiring daily phototherapy. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject has a diagnosis of Crigler-Najjar syndrome resulting from a confirmed mutation in the UGT1A1 gene as assessed by a Sponsor-approved testing facility. 2. Subject is aged ≥1 year. 3. Subject is prescribed daily phototherapy for a minimum of 6 hours within a 24-hour period (daily illumination time). 4. Signed informed consent by the subject's parent(s) or legally authorized representative(s) (LAR) (if applicable). 5. Subject and parent(s)/LAR(s) are willing and able to comply with study visits and study procedures. 6. Sexually active patients must be willing to use an acceptable method of contraception such as double barrier contraception during the study and for at least 3 months after dose of study treatment. 7. Females of childbearing potential must have a negative pregnancy test within 7 days of dosing and be willing to have additional pregnancy tests during the study. |
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E.4 | Principal exclusion criteria |
1. Subject is currently participating in an interventional study or has received gene or cell therapy. 2. Subject has received a whole liver, partial liver, or hepatocyte transplant; or subject has a liver transplant scheduled within the treatment period of this study. 3. Subject has significant cholestatic disease. 4. Subject is receiving phenobarbital or other known inducer of UGT1A1 within 30 days of screening. 5. Subject tests positive for AAV8 antibody with titers >1:20 (subjects under the age of 18 months may be retested in cases where antibodies may have been maternally acquired and titers may decline in the first months of life). 6. Other than as required per protocol, subject has received immune-modulating agents within 3 months before dosing (use of inhaled corticosteroids to manage chronic respiratory conditions is allowed); use of other concomitant medications to manage chronic conditions must have been stable for at least 4 weeks before dosing. 7. Subject has any clinically significant laboratory values, in the opinion of the investigator. 8. Subject has clinically significant underlying liver disease (other than CN). 9. Subject has a history of, or currently has, a clinically important condition other than CN, in the opinion of the investigator. 10. Female subject breastfeeding at screening or planning to become pregnant at any time during study participation. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Change in total serum bilirubin - Change in number of hours of phototherapy over a 24-hour period. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- Change in total serum bilirubin (Week 12 and 18) - Change in number of hours of phototherapy over a 24-hour period. (Week 18) |
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E.5.2 | Secondary end point(s) |
• Proportion of subjects with successful weaning off of phototherapy • A composite endpoint based on change in bilirubin levels and hours of phototherapy • UGT protein expression, DNA, and RNA levels from liver biopsy |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Proportion of subjects with successful weaning off of phototherapy (at 24 weeks) • A composite endpoint based on change in bilirubin levels and hours of phototherapy (at 18 weeks) • UGT protein expression, DNA, and RNA levels from liver biopsy (at 24 weeks) |
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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 | Yes |
E.8.1.1 | Randomised | Yes |
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 |
Non-treatment concurrent control |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 6 |
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 | 6 |
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 |