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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2011 by Alfact Innovation.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Alfact Innovation
ClinicalTrials.gov Identifier:
NCT01318525
First received: March 17, 2011
Last updated: April 4, 2011
Last verified: April 2011
  Purpose

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.


Condition Intervention Phase
Liver Failure, Acute
Drug: ALF-5755
Drug: Saline solution (0.9% NaCl)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Alfact Innovation:

Primary Outcome Measures:
  • Rate of change of Prothrombin Rate initiation [ Time Frame: Over a period of 72 hours from baseline ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Rate of change of Factor V (FV) plasma level [ Time Frame: Over a period of 72 hours from baseline ] [ Designated as safety issue: No ]
  • Rate of change of international normalized ratio (INR) [ Time Frame: Over a period of 72 hours from baseline ] [ Designated as safety issue: No ]
  • Rate of change of alanine transaminases (ALT) plasma level [ Time Frame: Over a period of 72 hours from baseline ] [ Designated as safety issue: No ]
  • Rate of change of aspartate transaminases (AST) plasma level [ Time Frame: Over a period of 72 hours from baseline ] [ Designated as safety issue: No ]
  • Change of Hepatic Encephalopathy Grade (HE grade) [ Time Frame: Over a period of 72 hours from baseline ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: October 2010
Estimated Study Completion Date: September 2012
Estimated Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ALF-5755 Drug: ALF-5755
10 mg (25 ml) given in slow intravenous infusion over 10 minutes with an automatic syringe
Placebo Comparator: Saline solution (0.9% NaCl) Drug: Saline solution (0.9% NaCl)
25 ml given in slow intravenous infusion over 10 minutes with an automatic syringe

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01318525

Contacts
Contact: Paul Amouyal +33 1 45 59 35 66 amouyal.paul@wanadoo.fr

Locations
France
CHU de Besançon Not yet recruiting
Besançon Cedex, France, 25030
Principal Investigator: Vincent Di Martino         
CHU Clermont-Ferrand Not yet recruiting
Clermont-Ferrand Cedex 1, France, 63003
Principal Investigator: Armand Abergel         
Hôpital Beaujon Recruiting
Clichy, France, 92110
Principal Investigator: François Durand         
CHU de Grenoble Recruiting
Grenoble Cedex 9, France, 38043
Principal Investigator: Vincent Leroy         
Hôpital Claude Huriez Not yet recruiting
Lille cedex, France, 59037
Principal Investigator: Philippe Mathurin         
Hôpital Croix-Rousse Recruiting
Lyon, France, 69004
Principal Investigator: Si Nafa Si Ahmed         
Hôpital Conception Not yet recruiting
Marseille Cedex 5, France, 13385
Principal Investigator: Danielle Botta Fridlund         
Hôpital Saint-Eloi Recruiting
Montpellier Cedex 5, France, 34295
Principal Investigator: Dominique Larrey         
Hôpital de l'Archet 2 Not yet recruiting
Nice, France, 06202
Principal Investigator: Jean Gugenheim         
Hôpital Saint Antoine Recruiting
Paris Cedex 12, France, 75571
Principal Investigator: Nicolas Carbonell         
Hôpital La Pitié Salpétrière Recruiting
Paris Cedex 13, France, 75651
Principal Investigator: Marika Rudler         
Centre Hépatobiliaire Paul Brousse Recruiting
Villejuif Cedex, France, 94804
Principal Investigator: Didier Samuel         
Sponsors and Collaborators
Alfact Innovation
Investigators
Study Director: Paul Amouyal Alfact Innovation
  More Information

Publications:

Responsible Party: Paul Amouyal, Alfact Innovation
ClinicalTrials.gov Identifier: NCT01318525     History of Changes
Other Study ID Numbers: ALF-5755_P2_ALF
Study First Received: March 17, 2011
Last Updated: April 4, 2011
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:
Hepatitis
Liver Failure
Liver Failure, Acute
Liver Diseases
Digestive System Diseases
Hepatic Insufficiency

ClinicalTrials.gov processed this record on July 28, 2014