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

March 17, 2011
April 4, 2011
October 2010
May 2012   (final data collection date for primary outcome measure)
Rate of change of Prothrombin Rate initiation [ Time Frame: Over a period of 72 hours from baseline ] [ Designated as safety issue: No ]
Rate of change of Prothrombin Rate initiation [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01318525 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Rate of change of Factor V (FV) plasma level [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
  • Rate of change of international normalized ratio (INR) [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
  • Rate of change of alanine transaminases (ALT) plasma level [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
  • Rate of change of aspartate transaminases (AST) plasma level [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
  • Change of Hepatic Encephalopathy Grade (HE grade) [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Efficacy & Safety of ALF-5755 in Patients With Nonacetaminophen Severe Acute Hepatitis & Early Stage Acute Liver Failure
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.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Liver Failure, Acute
  • Drug: ALF-5755
    10 mg (25 ml) given in slow intravenous infusion over 10 minutes with an automatic syringe
  • Drug: Saline solution (0.9% NaCl)
    25 ml given in slow intravenous infusion over 10 minutes with an automatic syringe
  • Experimental: ALF-5755
    Intervention: Drug: ALF-5755
  • Placebo Comparator: Saline solution (0.9% NaCl)
    Intervention: Drug: Saline solution (0.9% NaCl)

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
60
September 2012
May 2012   (final data collection date for primary outcome measure)

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.
Both
18 Years to 65 Years
No
Contact: Paul Amouyal +33 1 45 59 35 66 amouyal.paul@wanadoo.fr
France
 
NCT01318525
ALF-5755_P2_ALF
Yes
Paul Amouyal, Alfact Innovation
Alfact Innovation
Not Provided
Study Director: Paul Amouyal Alfact Innovation
Alfact Innovation
April 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP