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

NCT ID: NCT01318525

Last Updated: 2011-04-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-10-31

Study Completion Date

2012-09-30

Brief Summary

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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.

Detailed Description

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Conditions

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Liver Failure, Acute

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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ALF-5755

Group Type EXPERIMENTAL

ALF-5755

Intervention Type DRUG

10 mg (25 ml) given in slow intravenous infusion over 10 minutes with an automatic syringe

Saline solution (0.9% NaCl)

Group Type PLACEBO_COMPARATOR

Saline solution (0.9% NaCl)

Intervention Type DRUG

25 ml given in slow intravenous infusion over 10 minutes with an automatic syringe

Interventions

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ALF-5755

10 mg (25 ml) given in slow intravenous infusion over 10 minutes with an automatic syringe

Intervention Type DRUG

Saline solution (0.9% NaCl)

25 ml given in slow intravenous infusion over 10 minutes with an automatic syringe

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Alfact Innovation

INDUSTRY

Sponsor Role lead

Responsible Party

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Alfact Innovation

Principal Investigators

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Paul Amouyal

Role: STUDY_DIRECTOR

Alfact Innovation

Locations

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CHU de Besançon

Besançon, , France

Site Status NOT_YET_RECRUITING

CHU Clermont-Ferrand

Clermont-Ferrand, , France

Site Status NOT_YET_RECRUITING

Hôpital Beaujon

Clichy, , France

Site Status RECRUITING

CHU de Grenoble

Grenoble, , France

Site Status RECRUITING

Hôpital Claude Huriez

Lille, , France

Site Status NOT_YET_RECRUITING

Hôpital Croix-Rousse

Lyon, , France

Site Status RECRUITING

Hôpital Conception

Marseille, , France

Site Status NOT_YET_RECRUITING

Hôpital Saint-Eloi

Montpellier, , France

Site Status RECRUITING

Hôpital de l'Archet 2

Nice, , France

Site Status NOT_YET_RECRUITING

Hôpital Saint Antoine

Paris, , France

Site Status RECRUITING

Hôpital La Pitié Salpétrière

Paris, , France

Site Status RECRUITING

Centre Hépatobiliaire Paul Brousse

Villejuif, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Paul Amouyal

Role: CONTACT

+33 1 45 59 35 66

References

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Christa L, Felin M, Morali O, Simon MT, Lasserre C, Brechot C, Seve 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. doi: 10.1016/0014-5793(94)80640-3.

Reference Type BACKGROUND
PMID: 8276102 (View on PubMed)

Hoofnagle JH, Carithers RL Jr, Shapiro C, Ascher N. Fulminant hepatic failure: summary of a workshop. Hepatology. 1995 Jan;21(1):240-52.

Reference Type BACKGROUND
PMID: 7806160 (View on PubMed)

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. doi: 10.1016/j.bbagen.2005.01.002. Epub 2005 Jan 21.

Reference Type BACKGROUND
PMID: 15715980 (View on PubMed)

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. doi: 10.1038/nm0497-409.

Reference Type BACKGROUND
PMID: 9095174 (View on PubMed)

Lasserre C, Christa L, Simon MT, Vernier P, Brechot C. A novel gene (HIP) activated in human primary liver cancer. Cancer Res. 1992 Sep 15;52(18):5089-95.

Reference Type BACKGROUND
PMID: 1325291 (View on PubMed)

Lieu HT, Batteux F, Simon MT, Cortes A, Nicco C, Zavala F, Pauloin A, Tralhao JG, Soubrane O, Weill B, Brechot C, Christa L. HIP/PAP accelerates liver regeneration and protects against acetaminophen injury in mice. Hepatology. 2005 Sep;42(3):618-26. doi: 10.1002/hep.20845.

Reference Type BACKGROUND
PMID: 16116631 (View on PubMed)

Lieu HT, Simon MT, Nguyen-Khoa T, Kebede M, Cortes A, Tebar L, Smith AJ, Bayne R, Hunt SP, Brechot 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. doi: 10.1002/hep.21434.

Reference Type BACKGROUND
PMID: 17133485 (View on PubMed)

Polson J, Lee WM; American Association for the Study of Liver Disease. AASLD position paper: the management of acute liver failure. Hepatology. 2005 May;41(5):1179-97. doi: 10.1002/hep.20703. No abstract available.

Reference Type BACKGROUND
PMID: 15841455 (View on PubMed)

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. doi: 10.1096/fj.02-1013com.

Reference Type BACKGROUND
PMID: 12890698 (View on PubMed)

Nalpas B, Ichai P, Jamot L, Carbonell N, Rudler M, Mathurin P, Durand F, Gerken G, Manns M, Trautwein C, Larrey D, Radenne S, Duvoux C, Leroy V, Bernuau J, Faivre J, Moniaux N, Brechot C, Amouyal G, Amouyal P, Samuel D. A Proof of Concept, Phase II Randomized European Trial, on the Efficacy of ALF-5755, a Novel Extracellular Matrix-Targeted Antioxidant in Patients with Acute Liver Diseases. PLoS One. 2016 Mar 16;11(3):e0150733. doi: 10.1371/journal.pone.0150733. eCollection 2016.

Reference Type DERIVED
PMID: 26983031 (View on PubMed)

Other Identifiers

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ALF-5755_P2_ALF

Identifier Type: -

Identifier Source: org_study_id

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