Back to resultsEfficacy & Safety of ALF-5755 in Patients With Nonacetaminophen Severe Acute Hepatitis & Early Stage Acute Liver Failure
Primary Purpose
Liver Failure, Acute
Status
Unknown status
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
ALF-5755
Saline solution (0.9% NaCl)
Sponsored by
About this trial
This is an interventional treatment trial for Liver Failure, Acute
Eligibility 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.
Sites / Locations
- CHU de Besançon
- CHU Clermont-Ferrand
- Hôpital BeaujonRecruiting
- CHU de GrenobleRecruiting
- Hôpital Claude Huriez
- Hôpital Croix-RousseRecruiting
- Hôpital Conception
- Hôpital Saint-EloiRecruiting
- Hôpital de l'Archet 2
- Hôpital Saint AntoineRecruiting
- Hôpital La Pitié SalpétrièreRecruiting
- Centre Hépatobiliaire Paul BrousseRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
ALF-5755
Saline solution (0.9% NaCl)
Arm Description
Outcomes
Primary Outcome Measures
Rate of change of Prothrombin Rate initiation
Secondary Outcome Measures
Rate of change of Factor V (FV) plasma level
Rate of change of international normalized ratio (INR)
Rate of change of alanine transaminases (ALT) plasma level
Rate of change of aspartate transaminases (AST) plasma level
Change of Hepatic Encephalopathy Grade (HE grade)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01318525
Brief Title
Efficacy & Safety of ALF-5755 in Patients With Nonacetaminophen Severe Acute Hepatitis & Early Stage Acute Liver Failure
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2011
Overall Recruitment Status
Unknown status
Study Start Date
October 2010 (undefined)
Primary Completion Date
May 2012 (Anticipated)
Study Completion Date
September 2012 (Anticipated)
3. Sponsor/Collaborators
Name of the Sponsor
Alfact Innovation
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liver Failure, Acute
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
ALF-5755
Arm Type
Experimental
Arm Title
Saline solution (0.9% NaCl)
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
ALF-5755
Intervention Description
10 mg (25 ml) given in slow intravenous infusion over 10 minutes with an automatic syringe
Intervention Type
Drug
Intervention Name(s)
Saline solution (0.9% NaCl)
Intervention Description
25 ml given in slow intravenous infusion over 10 minutes with an automatic syringe
Primary Outcome Measure Information:
Title
Rate of change of Prothrombin Rate initiation
Time Frame
Over a period of 72 hours from baseline
Secondary Outcome Measure Information:
Title
Rate of change of Factor V (FV) plasma level
Time Frame
Over a period of 72 hours from baseline
Title
Rate of change of international normalized ratio (INR)
Time Frame
Over a period of 72 hours from baseline
Title
Rate of change of alanine transaminases (ALT) plasma level
Time Frame
Over a period of 72 hours from baseline
Title
Rate of change of aspartate transaminases (AST) plasma level
Time Frame
Over a period of 72 hours from baseline
Title
Change of Hepatic Encephalopathy Grade (HE grade)
Time Frame
Over a period of 72 hours from baseline
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Paul Amouyal
Phone
+33 1 45 59 35 66
Email
amouyal.paul@wanadoo.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul Amouyal
Organizational Affiliation
Alfact Innovation
Official's Role
Study Director
Facility Information:
Facility Name
CHU de Besançon
City
Besançon Cedex
ZIP/Postal Code
25030
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vincent Di Martino
Facility Name
CHU Clermont-Ferrand
City
Clermont-Ferrand Cedex 1
ZIP/Postal Code
63003
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Armand Abergel
Facility Name
Hôpital Beaujon
City
Clichy
ZIP/Postal Code
92110
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
François Durand
Facility Name
CHU de Grenoble
City
Grenoble Cedex 9
ZIP/Postal Code
38043
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vincent Leroy
Facility Name
Hôpital Claude Huriez
City
Lille cedex
ZIP/Postal Code
59037
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Philippe Mathurin
Facility Name
Hôpital Croix-Rousse
City
Lyon
ZIP/Postal Code
69004
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Si Nafa Si Ahmed
Facility Name
Hôpital Conception
City
Marseille Cedex 5
ZIP/Postal Code
13385
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Danielle Botta Fridlund
Facility Name
Hôpital Saint-Eloi
City
Montpellier Cedex 5
ZIP/Postal Code
34295
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dominique Larrey
Facility Name
Hôpital de l'Archet 2
City
Nice
ZIP/Postal Code
06202
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jean Gugenheim
Facility Name
Hôpital Saint Antoine
City
Paris Cedex 12
ZIP/Postal Code
75571
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nicolas Carbonell
Facility Name
Hôpital La Pitié Salpétrière
City
Paris Cedex 13
ZIP/Postal Code
75651
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marika Rudler
Facility Name
Centre Hépatobiliaire Paul Brousse
City
Villejuif Cedex
ZIP/Postal Code
94804
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Didier Samuel
12. IPD Sharing Statement
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Efficacy & Safety of ALF-5755 in Patients With Nonacetaminophen Severe Acute Hepatitis & Early Stage Acute Liver Failure
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