E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute Intermittent Porphyria (AIP) |
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E.1.1.1 | Medical condition in easily understood language |
A rare metabolic disorder caused by a genetic mutation which leads to deficiency of the enzyme PBGD causing severe abdominal pain, and cardiovascular, neurologic and psychiatric dysfunction |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
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 | 10000818 |
E.1.2 | Term | Acute intermittent porphyria |
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 |
To evaluate the long-term safety and tolerability of ALN-AS1 in patients with AIP. |
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E.2.2 | Secondary objectives of the trial |
• Assess the PD effect of ALN-AS1 over time
• Assess the clinical activity of ALN-AS1 over time |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Completed and, in the opinion of the Investigator, tolerated study drug dosing in Part C of study ALN-AS1-001
2. Not on a scheduled regimen of hemin to prevent porphyria attacks at Screening
3. Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test, cannot be breast feeding, and must be willing to use 1 highly effective method of contraception 14 days before first dose, throughout study participation, and for 90 days after last dose administration
4. Willing and able to comply with the study requirements and to provide written informed consent. |
|
E.4 | Principal exclusion criteria |
1. Alanine transaminase ≥2.0×ULN or total bilirubin ≥2 mg/dL (unless bilirubin elevation is due to Gilbert’s syndrome)
2. Estimated glomerular filtration rate ≤30 mL/min/1.73 m2 (using the Modification of Diet in Renal Disease formula)
3. History of multiple drug allergies or history of allergic reaction to an oligonucleotide or to N-acetyl galactosamine ligand
4. Received an investigational agent, other than ALN-AS1, or who are in follow-up of another clinical study of an investigational agent within 90 days before study drug administration
5. Other medical conditions or comorbidities which, in the opinion of the Investigator, would interfere with study compliance or data interpretation. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Patient incidence of adverse events |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The duration of treatment is up to 48 months. The estimated total time on study, inclusive of Screening/Baseline, for each patient is up to 56 months |
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E.5.2 | Secondary end point(s) |
• Change in urine ALA and PBG levels
• Frequency and characteristics of porphyria attacks
• Change in hemin administration. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The duration of treatment is up to 48 months. The estimated total time on study, inclusive of Screening/Baseline, for each patient is up to 56 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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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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.8.2.4 | 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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 |
Sweden |
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 | 5 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 8 |