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

Alfact Innovation

Status and phase

Unknown

Phase 2

Conditions

Liver Failure, Acute

Treatments

Drug: ALF-5755

Drug: Saline solution (0.9% NaCl)

Study type

Interventional

Funder types

Industry

Identifiers

NCT01318525

ALF-5755_P2_ALF

Details and patient eligibility

About

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.

Enrollment

60 estimated patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

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.