Liver Failure, Acute Clinical Trial
Official title:
A Multicentre, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Efficacy and the Safety of ALF-5755 in Patients With Nonacetaminophen Severe Acute Hepatitis and Early Stage Acute Liver Failure
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.
Status | Recruiting |
Enrollment | 60 |
Est. completion date | September 2012 |
Est. primary completion date | May 2012 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years to 65 Years |
Eligibility |
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. |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
France | CHU de Besançon | Besançon Cedex | |
France | CHU Clermont-Ferrand | Clermont-Ferrand Cedex 1 | |
France | Hôpital Beaujon | Clichy | |
France | CHU de Grenoble | Grenoble Cedex 9 | |
France | Hôpital Claude Huriez | Lille cedex | |
France | Hôpital Croix-Rousse | Lyon | |
France | Hôpital Conception | Marseille Cedex 5 | |
France | Hôpital Saint-Eloi | Montpellier Cedex 5 | |
France | Hôpital de l'Archet 2 | Nice | |
France | Hôpital Saint Antoine | Paris Cedex 12 | |
France | Hôpital La Pitié Salpétrière | Paris Cedex 13 | |
France | Centre Hépatobiliaire Paul Brousse | Villejuif Cedex |
Lead Sponsor | Collaborator |
---|---|
Alfact Innovation |
France,
Christa L, Felin M, Morali O, Simon MT, Lasserre C, Brechot C, Sève AP. The human HIP gene, overexpressed in primary liver cancer encodes for a C-type carbohydrate binding protein with lactose binding activity. FEBS Lett. 1994 Jan 3;337(1):114-8. — View Citation
Hoofnagle JH, Carithers RL Jr, Shapiro C, Ascher N. Fulminant hepatic failure: summary of a workshop. Hepatology. 1995 Jan;21(1):240-52. Review. — View Citation
Iovanna JL, Dagorn JC. The multifunctional family of secreted proteins containing a C-type lectin-like domain linked to a short N-terminal peptide. Biochim Biophys Acta. 2005 May 25;1723(1-3):8-18. Epub 2005 Jan 21. Review. — View Citation
Kondo T, Suda T, Fukuyama H, Adachi M, Nagata S. Essential roles of the Fas ligand in the development of hepatitis. Nat Med. 1997 Apr;3(4):409-13. — View Citation
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Lieu HT, Simon MT, Nguyen-Khoa T, Kebede M, Cortes A, Tebar L, Smith AJ, Bayne R, Hunt SP, Bréchot C, Christa L. Reg2 inactivation increases sensitivity to Fas hepatotoxicity and delays liver regeneration post-hepatectomy in mice. Hepatology. 2006 Dec;44(6):1452-64. — View Citation
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Simon MT, Pauloin A, Normand G, Lieu HT, Mouly H, Pivert G, Carnot F, Tralhao JG, Brechot C, Christa L. HIP/PAP stimulates liver regeneration after partial hepatectomy and combines mitogenic and anti-apoptotic functions through the PKA signaling pathway. FASEB J. 2003 Aug;17(11):1441-50. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Rate of change of Prothrombin Rate initiation | Over a period of 72 hours from baseline | No | |
Secondary | Rate of change of Factor V (FV) plasma level | Over a period of 72 hours from baseline | No | |
Secondary | Rate of change of international normalized ratio (INR) | Over a period of 72 hours from baseline | No | |
Secondary | Rate of change of alanine transaminases (ALT) plasma level | Over a period of 72 hours from baseline | No | |
Secondary | Rate of change of aspartate transaminases (AST) plasma level | Over a period of 72 hours from baseline | No | |
Secondary | Change of Hepatic Encephalopathy Grade (HE grade) | Over a period of 72 hours from baseline | No |
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