Efficacy & Safety of ALF-5755 in Patients With Nonacetaminophen Severe Acute Hepatitis & Early Stage Acute Liver Failure

Phase 2

• Conditions: Liver Failure, Acute
• Interventions: Drug: ALF-5755; Drug: Saline solution (0.9% NaCl)

• Registration Number: NCT01318525
• Lead Sponsor: Alfact Innovation

Brief Summary

Acute liver failure is a rare but dramatic disease, often affecting young people, marked by the sudden loss of liver function in a person without preexisting liver disease.

ALF-5755 has been shown to promote cell survival after apoptotic or oxidative stress, and liver cell regeneration in primary cultures and in vivo. ALF-5755 may become, in this dramatic disease with high unmet medical need, a future therapy for the treatment of patients suffering from severe acute hepatitis (SAH) and acute liver failure (ALF) not due to acetaminophen overdose, where liver transplantation is the sole treatment in the absence of spontaneous recovery.

The primary objective of the study is to evaluate the efficacy of ALF-5755 versus placebo.

A minimum of 60 patients will be recruited into the study in the following two treatment groups:

* Group A: approximately 30 patients will receive ALF-5755

* Group B: approximately 30 patients will receive placebo (physiological saline solution: 0.9% NaCl)

Patients will receive 10 mg (25 ml) of ALF5755 or placebo every 12 hours over 3 days in slow intravenous infusions over 10 minutes using automatic syringes.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-10
• Study First Submitted: 2011-03-17
• Study First Submitted QC: 2011-03-17
• Study First Posted: 2011-03-18
• Status Verified: 2011-04
• Last Update Submitted: 2011-04-04
• Last Update Posted: 2011-04-05
• Primary Completion: 2012-05
• Study Completion: 2012-09

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• A signed written informed consent from patient or from patient's next of kin or from an authorized person according to local procedures
• 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 chronic liver disease
• Patient who can receive first treatment dose within the first 48 hours after biological baseline assessment
• Age ≥ 18 and ≤ 65 years
• 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
• Patient affiliated to social security insurance system.

Exclusion Criteria

• Acetaminophen-induced hepatitis defined as acetaminophen intake > 4 g/day, at least once in the 7 days prior to baseline
• Shock liver (ischemic hepatopathy) OR HELLP syndrome OR Budd-Chiari syndrome OR intrahepatic malignancy
• Serum creatinine ≥ 180 μmol/L
• Body Mass Index (BMI) ≥ 35
• Septic shock requiring administration of inotropic drugs
• Uncontrolled active bleeding
• Patients who received fresh frozen plasma, PPSB (Prothrombin-Proconvertin-Stuart-B), or vitamin K infusion over the last 48 hours
• Patient receiving liver support device treatment, including but not exclusively bioartificial liver (BAL), Extracorporeal Liver Assist Device (ELAD), transgenic pig perfusion
• Patient receiving hemodialysis, hemofiltration or hemodiafiltration treatment
• Intractable arterial hypotension (arterial systolic blood pressure equal to or below 70 mmHg) present or require inotropic drugs at baseline
• Human Immunodeficiency Virus (HIV) positive patient
• Active cancer
• Pregnancy or breast-feeding
• Surgery within 4 weeks prior to baseline, or unsolved surgical disease outside liver transplantation.
• Patient included in another clinical trial within 4 weeks prior to baseline
• Patient with organ or bone-marrow allograft
• Absolute contra-indication to liver transplantation.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ALF-5755	ALF-5755	-
Saline solution (0.9% NaCl)	Saline solution (0.9% NaCl)	-

Primary Outcome Measures

Name	Time	Method
Rate of change of Prothrombin Rate initiation	Over a period of 72 hours from baseline

Secondary Outcome Measures

Name	Time	Method
Rate of change of Factor V (FV) plasma level	Over a period of 72 hours from baseline
Rate of change of international normalized ratio (INR)	Over a period of 72 hours from baseline
Rate of change of alanine transaminases (ALT) plasma level	Over a period of 72 hours from baseline
Rate of change of aspartate transaminases (AST) plasma level	Over a period of 72 hours from baseline
Change of Hepatic Encephalopathy Grade (HE grade)	Over a period of 72 hours from baseline

Trial Locations

Locations (12)

Hôpital Beaujon; 🇫🇷 Clichy, France

CHU Clermont-Ferrand; 🇫🇷 Clermont-Ferrand Cedex 1, France

CHU de Grenoble; 🇫🇷 Grenoble Cedex 9, France

Hôpital Croix-Rousse; 🇫🇷 Lyon, France

Hôpital Claude Huriez; 🇫🇷 Lille cedex, France

Hôpital Saint-Eloi; 🇫🇷 Montpellier Cedex 5, France

CHU de Besançon; 🇫🇷 Besançon Cedex, France

Hôpital Conception; 🇫🇷 Marseille Cedex 5, France

Centre Hépatobiliaire Paul Brousse; 🇫🇷 Villejuif Cedex, France

Hôpital La Pitié Salpétrière; 🇫🇷 Paris Cedex 13, France

Hôpital Saint Antoine; 🇫🇷 Paris Cedex 12, France

Hôpital de l'Archet 2; 🇫🇷 Nice, France