E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049844 |
E.1.2 | Term | Acute liver failure |
E.1.2 | System Organ Class | 10019805 - Hepatobiliary 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 evaluate the efficacy of ALF-5755 versus placebo, measured by rate of change of prothrombin ratio (PR) during the 72 hours following treatment initiation, in patients with nonacetaminophen SAH and early stage ALF. |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the safety and tolerability of ALF-5755 versus placebo in patients with nonacetaminophen SAH and early stage ALF. - To determine the pharmacokinetic (PK) parameters of ALF-5755 versus placebo in patients with nonacetaminophen SAH and early stage ALF. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patient must meet all inclusion criteria prior to randomization:
1.A signed written informed consent from patient or from patient's next of kin
2.Early stage acute liver failure OR severe acute hepatitis defined as: -15% ≤ PR < 50% -No hepatic encephalopathy, OR grade I or II encephalopathy (Appendix E) -Presumed acute illness onset of less than 26 weeks -No evidence of underlying cirrhosis
3.Patient who can receive first treatment dose within the first 12 hours after biological baseline assessment
4.Age ≥ 18 and ≤ 75 years
5.Contraception (only for females of childbearing potential) to be taken throughout the study until D21. Sole mechanic contraceptives, such as condoms, are advised. Note: Oral contraceptives may have contraindications in case of severe acute hepatitis and acute liver failure
6.Patient affiliated to social security insurance system. |
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E.4 | Principal exclusion criteria |
Patients who meet any of the following exclusion criteria are not eligible for randomization:
1.Acetaminophen-induced hepatitis defined as acetaminophen intake > 4 g/day, at least once in the 7 days prior to baseline
2.Shock liver (ischemic hepatopathy) OR HELLP syndrome OR Budd-Chiari syndrome OR intrahepatic malignancy
3.Serum creatinine ≥ 180 µmol/L
4.Body Mass Index (BMI) ≥ 35
5. Septic shock requiring administration of inotropic drugs
6.Uncontrolled active bleeding
7.Patients who received fresh frozen plasma, PPSB (Prothrombine-Proconvertine-Stuart-B), or vitamin K infusion over the last 24 hours
8.Patient receiving liver support device treatment, including but not exclusively bioartificial liver (BAL), Extracorporeal Liver Assist Device (ELAD), transgenic pig perfusion
9.Patient receiving hemodialysis, hemofiltration or hemodiafiltration treatment 10.Intractable arterial hypotension (arterial systolic blood pressure equal to or below 70 mmHg) present or require inotropic drugs at baseline
11.Human Immunodeficiency Virus (HIV) positive patient
12.Active cancer
13.Pregnancy or breast-feeding
14.Surgery within 4 weeks prior to baseline, or unsolved surgical disease outside liver transplantation.
15.Patient included in another clinical trial within 4 weeks prior to baseline 16.Patient with organ or bone-marrow allograft
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E.5 End points |
E.5.1 | Primary end point(s) |
Rate of change of PR during 72 hours following treatment initiation |
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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 | 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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
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.8.4.1 | 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 | 14 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |