Liver Failure, AcutePhase 2NCT01318525
Efficacy & Safety of ALF-5755 in Patients With Nonacetaminophen Severe Acute Hepatitis & Early Stage Acute Liver Failure
A Phase 2 study testing ALF-5755 and Saline solution (0.9% NaCl) in people with Liver Failure, Acute, run by Alfact Innovation at 12 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Liver Failure, Acute
- What is being tested?
- ALF-5755 and Saline solution (0.9% NaCl)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 12 sitesFrance
- Study dates
- Oct 2010to Sep 2012
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
Show all 17Show fewer
- 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.
Trial locations and contacts
12 sites in 1 country.
12 sites in 1 country
France12 sites, 12 recruiting
- Not yet recruiting
CHU de Besançon
Besançon, 25030
Vincent Di Martino
- Not yet recruiting
CHU Clermont-Ferrand
Clermont-Ferrand, 63003
Armand Abergel
- Recruiting
Hôpital Beaujon
Clichy, 92110
François Durand
- Recruiting
CHU de Grenoble
Grenoble, 38043
Vincent Leroy
- Not yet recruiting
Hôpital Claude Huriez
Lille, 59037
Philippe Mathurin
- Recruiting
Hôpital Croix-Rousse
Lyon, 69004
Si Nafa Si Ahmed
- Not yet recruiting
Hôpital Conception
Marseille, 13385
Danielle Botta Fridlund
- Recruiting
Hôpital Saint-Eloi
Montpellier, 34295
Dominique Larrey
- Not yet recruiting
Hôpital de l'Archet 2
Nice, 06202
Jean Gugenheim
- Recruiting
Hôpital Saint Antoine
Paris, 75571
Nicolas Carbonell
- Recruiting
Hôpital La Pitié Salpétrière
Paris, 75651
Marika Rudler
- Recruiting
Centre Hépatobiliaire Paul Brousse
Villejuif, 94804
Didier Samuel
About this study
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.
Read more
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.
- Conditions
- Liver Failure, Acute
- Being tested
- ALF-5755, Saline solution (0.9% NaCl)
- Medical subject headings
- Liver Failure, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ALF-5755Drug
10 mg (25 ml) given in slow intravenous infusion over 10 minutes with an automatic syringe
Saline solution (0.9% NaCl)Drug
25 ml given in slow intravenous infusion over 10 minutes with an automatic syringe
| Study group | Role | What they receive |
|---|---|---|
| ALF-5755 | Experimental | Not described Receives: Drug: ALF-5755 |
| Saline solution (0.9% NaCl) | Placebo comparator | Not described Receives: Drug: Saline solution (0.9% NaCl) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of change of Prothrombin Rate initiation
Measured: Over a period of 72 hours from baseline
Secondary outcomes (5)
Rate of change of Factor V (FV) plasma level
Measured: Over a period of 72 hours from baseline
Rate of change of international normalized ratio (INR)
Measured: Over a period of 72 hours from baseline
Rate of change of alanine transaminases (ALT) plasma level
Measured: Over a period of 72 hours from baseline
Rate of change of aspartate transaminases (AST) plasma level
Measured: Over a period of 72 hours from baseline
Change of Hepatic Encephalopathy Grade (HE grade)
Measured: Over a period of 72 hours from baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2011 (estimated)
- Study startOct 2010
- Primary completionMay 2012 (estimated)
- Study completionSep 2012 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Liver Failure, AcuteStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Alfact Innovation
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Paul Amouyal, Study director, Alfact Innovation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01318525
- Sponsor's protocol ID
- ALF-5755_P2_ALF
- Status last verified
- Apr 2011
- First submitted
- 17 Mar 2011
- Last updated
- 5 Apr 2011
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 8276102Hoofnagle JH, Carithers RL Jr, Shapiro C, Ascher N. Fulminant hepatic failure: summary of a workshop. Hepatology. 1995 Jan;21(1):240-52.
PubMed 7806160Iovanna 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.
PubMed 15715980Kondo 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.
PubMed 9095174Lasserre 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.
PubMed 1325291Lieu 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.
PubMed 16116631Lieu 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.
PubMed 17133485Polson 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.
PubMed 15841455Simon 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.
PubMed 12890698Nalpas 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.
PubMed 26983031
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01318525
- Acronym / sponsor ID
- ALF-5755_P2_ALF
- Conditions
- Liver Failure, Acute
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Alfact InnovationIndustry (pharma, biotech, devices)
- Study start
- Oct 2010
- Primary completion
- May 2012 (estimated)
- Study completion
- Sep 2012 (estimated)
- First posted
- 18 Mar 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ALF-5755 | Experimental | Drug: ALF-5755 |
| Saline solution (0.9% NaCl) | Placebo comparator | Drug: Saline solution (0.9% NaCl) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ALF-575510 mg (25 ml) given in slow intravenous infusion over 10 minutes with an automatic syringe | Drug | ALF-5755 |
| Saline solution (0.9% NaCl)25 ml given in slow intravenous infusion over 10 minutes with an automatic syringe | Drug | Saline solution (0.9% NaCl) |
Primary outcome
Rate of change of Prothrombin Rate initiation
Time frame: Over a period of 72 hours from baseline
5 secondary outcomes
Rate of change of Factor V (FV) plasma level
Time frame: Over a period of 72 hours from baseline
Rate of change of international normalized ratio (INR)
Time frame: Over a period of 72 hours from baseline
Rate of change of alanine transaminases (ALT) plasma level
Time frame: Over a period of 72 hours from baseline
Rate of change of aspartate transaminases (AST) plasma level
Time frame: Over a period of 72 hours from baseline
Change of Hepatic Encephalopathy Grade (HE grade)
Time frame: Over a period of 72 hours from baseline
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2011.
- Background: PubMed 8276102Christa 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.
- Background: PubMed 7806160Hoofnagle JH, Carithers RL Jr, Shapiro C, Ascher N. Fulminant hepatic failure: summary of a workshop. Hepatology. 1995 Jan;21(1):240-52.
- Background: PubMed 15715980Iovanna 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.
- Background: PubMed 9095174Kondo 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.
- Background: PubMed 1325291Lasserre 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.
- Background: PubMed 16116631Lieu 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.
- Background: PubMed 17133485Lieu 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.
- Background: PubMed 15841455Polson 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.
- Background: PubMed 12890698Simon 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.
- Derived from this study: PubMed 26983031Nalpas 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul Amouyal study director
Alfact Innovation
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ALF-5755 and Saline solution (0.9% NaCl) in people with Liver Failure, Acute, run by Alfact Innovation at 12 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 5 Apr 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Paul Amouyal (+33 1 45 59 35 66, amouyal.paul@wanadoo.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of change of Prothrombin Rate initiation (time frame: Over a period of 72 hours from baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01318525, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Apr 2011.