Fatty LiverPhase 2Aramchol_005NCT02279524
A Clinical Trial to Evaluate the Efficacy and Safety of Two Aramchol Doses Versus Placebo in Patients With NASH
A Phase 2 study testing Aramchol in people with Fatty Liver and Non-Alcoholic Steatohepatitis, run by Galmed Research and Development, Ltd. at 78 sites in 11 countries.
Trial summary
This is a multicenter, Phase IIb, randomized, double blind, placebo-controlled study designed to evaluate the efficacy and safety of two Aramchol doses in subjects that are 18 to 75 years of age, with Non-Alcoholic Steatohepatitis (NASH) confirmed by liver biopsy performed in a period of 6 months before entering the… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Fatty Liver, Non-Alcoholic Steatohepatitis, Liver Diseases
- What is being tested?
- Aramchol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 247 participants
- Where
- 78 sitesin 11 countries
- Study dates
- 29 Apr 2015to 22 May 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female age 18 to 75 years.
- BMI between 25kg/m2 to 40kg/m2 or waist circumference between 88 cm to 200 cm for women, and between 102 cm to 200 cm for men. If there is deviation above the upper limit, please consult the MRI center, to ensure that the machine is suitable for the patient.
- Known type II Diabetes Mellitus or pre-Diabetes according to American Diabetes Association. One of the following 3 criteria is needed for pre-Diabetes: Fasting Plasma Glucose > 100mg/dl (5.5 mmol/l) or 2hPG following 75g OGTT > 140 (7.8 mmol/l) mg/dl or HbA1c > 5.7%. HbA1c can be repeated at Investigator's discretion.
- Histologically proven Steatohepatitis on a diagnostic liver biopsy performed either during screening or within 6 months before screening visit, confirmed by central laboratory reading of the slides.(Steatosis ≥1 + inflammation ≥1 + ballooning ≥1).Total activity NAS score of 4 or more.
- Liver fat concentration in the liver of 5.5% or more as measured by NMRS.
- Biopsies with an activity NAS score of 4 or more.
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- Normal synthetic liver function (serum albumin >3.2g/dl, INR 0.8-1.2, conjugated bilirubin < 35 µmol/L).
- Understanding the nature of the study and signature of the written informed consent.
- Negative pregnancy test at study entry for females of child bearing potential.
- Females of child bearing potential practicing reliable contraception throughout the study period (including oral contraceptives) as well as negative pregnancy test at study entry.
- Hypertensive patients must be well controlled by stable dose of anti-hypertensive medication for at least 2 months prior to screening.
- Patients previously treated with vitamin E (>400IU/day), Polyunsaturated fatty acid (>2g/day) or Ursodeoxycholic acid or fish oil can be included if stopped or at least maintained on stable dose at least 3 months prior to diagnostic liver biopsy (and are not started during the trial). These treatments-dosages are allowed if they were stable for at least 12 months prior to biopsy and can remain stable throughout the study. (Dosages less than the amounts stated above are allowed without washout- or stable-period restrictions).
- For patients with type II Diabetes, glycaemia must be controlled (Glycosylated Hemoglobin A1c ≤9%) while any HbA1c change should not exceed 1.5% during 6 months prior to enrolment). Treatments with anti-diabetic medications (except for those mentioned in Exclusion 16) are permitted if glycaemia is self-monitored by the patient. HbA1c can be repeated at Investigator's discretion.
Who cannot join
- Patients with other active (acute or chronic) liver disease other than NASH (e.g. viral hepatitis, unless eradicated at least 3 years prior to screening; genetic hemochromatosis; Wilson disease; alpha 1antitripsin deficiency; alcohol liver disease; drug-induced liver disease) at the time of randomization.
- Patients with clinically or histologically documented liver cirrhosis
- Known alcohol and/or any other drug abuse or dependence in the last five years.
- Known history or presence of clinically significant cardiovascular, gastrointestinal, metabolic other than Diabetes Mellitus, neurologic, pulmonary, endocrine, psychiatric, neoplastic disorder or nephrotic syndrome, that in the opinion of the Investigator warrant exclusion from the study.
- Patients with familial (i.e., genetic) hypertriglyceridemia and familial (i.e., genetic) hypercholesterolemia.
- History or presence of any disease or condition known to interfere with the absorption distribution, metabolism or excretion of drugs including bile salt metabolites (e.g. inflammatory bowel disease (IBD)), previous intestinal (ileal or colonic) operation, chronic pancreatitis, celiac disease or previous vagotomy. Ongoing Chronic constipation
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- Patients with heart or brain pacemaker (i.e., implantable neurological devices).
- Surgery during the last three month before screening which involved stent implantation of metal devices (e.g. knee, hip etc.)
- Weight loss of more than 5% within 6 months prior to randomization.
- History of bariatric surgery within 5 years of liver biopsy.
- Uncontrolled arterial hypertension.
- Women who are pregnant and breast feeding.
- Diabetes Mellitus other than type II (type I, endocrinopathy, genetic syndromes etc.).
- Patients with HIV infection.
- Daily alcohol intake >20 g/day for women and >30 g/day for men (on average per day) as per medical history.
- Treatment with other anti-diabetic medications:
- GLP-1 receptor agonists and Thiazolidinediones (TZDs), unless started at least 12 months prior to biopsy and on stable dose for 6 months. In case of GLP-1 receptor agonists stopped, it should be at least 6 months before biopsy as per medical history.
- SGLT-2 Inhibitors, Metformin, fibrates, statins, insulin, DPP-4 inhibitors and sulfonylurea unless prescribed dose has been stable for the last 6 months prior to the biopsy.
- Treatment with Valproic acid, Tamoxifen, Methotrexate, Amiodarone or chronic treatment with anti-cholinergic agents, corticosteroids, high dose estrogen and tetracycline within 12 months prior to the screening visit.
- Chronic treatment with antibiotics (e.g. Rifaximin).
- Homeopathic and/or alternative treatments. Any treatment should be stopped during the screening period at least 48 hours before randomization.
- Uncontrolled hypothyroidism defined as Thyroid Stimulating hormone >2X the upper limit of normal (ULN). Thyroid dysfunction controlled for at least 6 months prior to screening is permitted.
- Patients with renal dysfunction eGFR< 40.
- Unexplained serum creatine phosphokinase (CPK) >3X the upper limit of normal (UNL). Patients with a reason for CPK elevation may have the measurement repeated prior to randomization; a CPK retest > 3X ULN leads to exclusion.
- Patients with condition(s) that makes them unsuitable to perform the NMRS (as determined by the PI or the MRI facility).
- Hypersensitivity to Aramchol or to any of the excipients in the tablets
- Hypersensitivity to cholic acid or bile acid sequestrants
Trial locations and contacts
78 sites in 11 countries.
78 sites in 11 countries
United States17 sites
University of Virginia Medical Center
Charlottesville, Virginia, 22908
Profil Institue for Clinical Research Inc.
Chula Vista, California, 91911
Texas Digestive Disease Consultants
Dallas, Texas, 75246
Duke University Medical Center
Durham, North Carolina, 27710
Brooke Army Medical Center
Fort Sam Houston, Texas, 78234
Indiana University
Indianapolis, Indiana, 46202
Gastroenterology Consultants of San Antonio
Live Oak, Texas, 78233
Cedars-Sinai Medical Center
Los Angeles, California, 90048
Mount Sinai
New York, New York, 10029
Columbia University Medical Center
New York, New York, 10032
California Liver Research Institute
Pasadena, California, 91105
Wake Research
Raleigh, North Carolina, 27612
Inland Empoire Liver Foundation
Rialto, California, 92377
Texas Liver Institute San Antonio
San Antonio, Texas, 78215
Clinical Trials of Texas
San Antonio, Texas, 78229
University of California Department of Medicine Division of Gastroenterology
San Diego, California, 92103
Orange County Research Center
Tustin, California, 92780
Italy13 sites
Spedali Civili di Brescia
Brescia
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milan
A.O. San Paolo
Milan
A.O. U. "Federico II" di Napoli
Naples
Azienda Ospedaliera di Rilievo Nazionale "A.Cardarelli"
Naples
Azienda Ospidaliera Universitaria Seconda Universita di Napoli
Naples
A.O.U. Maggiore della Carità
Novara
"Ospedale Cristo Re" dell'Istituto Figlie di N.S. al Monte Calvario
Roma
Fondazione Policlinico di Tor Vergata
Roma
Ospedale San Camillo
Roma
Policlinico A. Gemelli
Roma
Policlinico Umberto I Di Roma
Roma
Policlinico Univestitario Campus Biomedico
Roma
Mexico10 sites
JM Research
Cuernavaca
Consultorio Médico
Metepec
Torre de Consultorios Clinica Londres
Mexico City, 06700
Consultorio Medico del Dr. Mauricio Castillo Barradas
Mexico City
Consultorio Medico
Mexico City
Instituto de Ciencias Medicas y de la Nutricion Salvador Zubiran
Mexico City
Torre de Consultorios Clinica Londres
Mexico City
Unidad de Hígado Hospital Universitario Dr. José Eleuterio González
Monterrey, Nuevo León
Accelerium Clinical Research
Monterrey
"Angeles Valle oriente" Hospital
San Pedro Garza García
France8 sites
Centre Hospitalier Universitaire (CHU) d'Angers
Angers
Centre Hospitalier Universitaire Dijon Bourgogne
Dijon
San Joseph Service Hepato Gastro Entrologie
Marseille
Hospital Saint Eloi
Montpellier
CHU Centre Hospiatalier Universitaire de Rennes
Paris
Hospital Pitie-Salpetriere
Paris
Hospital Saint-Antoine AP-HP
Paris
Hopital Paul Brousse
Villejuif
Israel8 sites
Carmel Medical Center
Haifa
Rambam Medical Center
Haifa
Hadassah Ein Karem Medical Cente
Jerusalem
Naharia Medical Center
Nahariya
The Holy family Medical Center
Nazareth
Sheba Medical Center
Ramat Gan
Tel-Aviv Saurasky Medical Center
Tel Aviv
Asaf Harofeh Medical Center
Zrifin
Chile5 sites
Biomedica Research Group
Santiago
Centro de Investigacion Clinica CEIC
Santiago
Hospital Clinico Universidad de Chile
Santiago
Pontificia Universidad Catolica de Chile
Santiago
Centro de Investigaciones Clinicas Vina del Mar
Viña del Mar
Georgia5 sites
Unimed Adjara
Batumi
Clinic Cortex
Tbilisi
David Tatishvili Medical Center
Tbilisi
LTD Diacor
Tbilisi
Research Institute of Clinical Medicine
Tbilisi
Romania5 sites
Clinical Institute Colentina
Bucharest
The National Institute for Infectious Diseases "Prof. Dr. Matei Bals", Clinical Department for Adults II
Bucharest
Cluj County Emergency Hospital
Cluj-Napoca, 400013
TVM Medical
Cluj-Napoca, 400013
County Hospital Mures-Gastroenterology Department
Târgu Mureş
Germany3 sites
Medizinische Hochschule
Hanover
EUGASTRO GmbH
Leipzig
Universitat Leipzig Medizinische Fakultat
Leipzig
Lithuania3 sites
Hospital of Lithuanian University of Health Sciences Kaunas Clinics
Kaunas
Klaipeda University Hospital
Klaipėda
Vilinius University Hospital Santariskiu Klinikos
Vilnius
About this study
Official title: A Phase IIb, Double Blind Randomized, Controlled Clinical Trial, to Evaluate the Efficacy and Safety of Two Aramchol Doses Versus Placebo in Patients With Non-Alcoholic Steatohepatitis (NASH) - Aramchol 005 Study
This is a multicenter, Phase IIb, randomized, double blind, placebo-controlled study designed to evaluate the efficacy and safety of two Aramchol doses in subjects that are 18 to 75 years of age, with Non-Alcoholic Steatohepatitis (NASH) confirmed by liver biopsy performed in a period of 6 months before entering the study, with overweight or obesity and who are pre diabetic or type II diabetic.
Eligible subjects will be enrolled into three treatments arms: Aramchol 400 and 600 mg tablets and placebo tablets in ratio 2:2:1.
The subjects will be evaluated at study sites for 11 scheduled visits during one year (52 weeks). After completion of the study treatment period, the subjects will be followed for an additional period of 13 weeks without study medication (until visit 11 (week 65)).
Read the detailed description
This is a multicenter, Phase IIb, randomized, double blind, placebo-controlled study designed to evaluate the efficacy and safety of two Aramchol doses in subjects that are 18 to 75 years of age, with Non-Alcoholic Steatohepatitis (NASH) confirmed by liver biopsy performed in a period of 6 months before entering the study, with overweight or obesity and who are pre diabetic or type II diabetic.
Eligible subjects will be enrolled into three treatments arms: Aramchol 400 and 600 mg tablets and placebo tablets in ratio 2:2:1.
The subjects will be evaluated at study sites for 11 scheduled visits: at screening (visit 1(weeks -4 - 0)), baseline (visit 2 (day 0)), visit 3 (week 2), visit 4 week 4), visit 5 (week 8), visit 6 (week 12), visit 7 (week 24), visit 8 (week 32), visit 9 (week 40) and visit 10 (week 52 - (End of Treatment/early termination visit)). After completion of the study treatment period, the subjects will be followed for an additional period of 13 weeks without study medication (until visit 11 (week 65)).
During the screening period, the severity of the disease will be evaluated with blood tests, liver biopsy and NMRS.
During the study the following assessments will be performed:
- Vital signs will be measured at each study visit.
- A physical examination will be performed at the screening visit, 24 weeks, End of Treatment/early termination and week 65 visit.
The following blood tests will be performed: complete blood count (CBC), serum chemistry (including electrolytes, liver enzymes, direct and total bilirubin, glucose, lipid profile which include triglyceride, cholesterol, HDL, LDL and VLDL, CPK, creatinine, urea, albumin, alkaline phosphatase), ESR and urinalysis during the screening visit, baseline, week 2, 4, 8, 24, 40, 52 and 65 (end of follow up) visits. Serology (HBV, HCV and HIV) will be performed during the screening visit. Coagulation (fibrinogen, PT/INR, aPTT) will be measured during screening and at baseline, week 24, End of Treatment/early termination and week 65 visits. Insulin (HOMA) will be measured during the screening, at week 24 and End of Treatment/early termination visits. HbA1C will be measured during the screening, at week 8, 24, 40 and End of Treatment/early termination visits. C reactive protein, Leptin and Adiponectin will be measured during baseline visit and at end of treatment period. The blood samples taken at these visits, will be tested for possible biomarkers. TSH, T3 and T4 will be measured during the screening visit. beta-hCG in women of childbearing potential will be performed during the screening visit. A serum sample will be collected and kept frozen until study end in case special investigation needs to be performed. This sample will be collected during the screening and visit 10/Early Termination.
- Body weight and waist circumference will be measured in screening, baseline, week 24, end of treatment and week 65 visits. Height will be measured during the screening visit.
- ECG will be performed during the screening visit, visit 7 (week 24) and end of treatment visits.
- All subjects will undergo two NMRS scans, at screening and end of treatment visits.
- FibroMax test will be performed only if the investigator thinks it is necessary
- Liver biopsy will be conducted during the screening and end of treatment visit. The biopsy in the screening visit will be performed only if it was not done within the 6 months prior to this visit.
- Metabolomics blood test will be performed at the screening, visit 7 and the End-of-Treatment/Early Termination visits. From some consenting patients (about 15) a sample from the liver biopsy will be taken for analysis.
- Endothelial Function will be conducted in selected sites. The test will be conducted during the baseline visit before the study treatment will be given and End of Treatment/early termination visit.
- Blood sample for Aramchol trough level will be collected (pre-dose) from patients in Israel at baseline (visit 2) week 4 (visit 4), week 12 (visit 6), week 24 (visit 7), week 40 (visit 9), end of treatment (visit 10) and follow up (visit 11). At selected sites in Mexico, USA and Hong Kong one blood sample will be collected (pre-dose) on visit 4 (up to 10 subjects per country) to test for trough Aramchol blood level differences between populations (e.g., African American, Asian, Hispanic).
- Blood sample for gene analysis will be taken from all consenting patients during the baseline visit, will be kept frozen and analyzed only at the study end.
- Life style questionnaire will be completed at all visits.
- Adverse events will be monitored throughout the study.
- Concomitant Medications will be monitored throughout the study.
- Telephone contacts will be performed on week 16, 20, 28, 36, 44 and 48. An interim safety analysis will be conducted as soon as 120 subjects will completed the follow up period of 24 weeks under study treatment. An independent DSMB will analyze the safety data and recommend a continued course of action. All patients will continue to be treated under the study protocol until conclusion of the analysis will be known.
Safety assessment will include frequency and severity of treatment-emergent AEs, clinically significant laboratory abnormalities, ECG changes and physical examination findings.
- Being tested
- Aramchol
- Keywords
- NASH, fibroses, obesity, diabetes
- Medical subject headings
- Fatty Liver, Non-alcoholic Fatty Liver Disease, Liver Diseases, Liver Cirrhosis, Fibrosis, Obesity, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AramcholDrug
Also called Placebo
Subjects will be administered Aramchol as follows:
- One tablet of Aramchol 400 mg and one tablet of matching placebo for Aramchol.
- One tablet of Aramchol 400 mg and one tablet of Aramchol 200 mg.
- Two tablet of Aramchol matching placebo. The tablets should be taken orally in the morning within 30 min after breakfast with a glass of water (250 ml).
Subjects are allowed to omit study drugs up to 3 consecutive days during the study.
| Study group | Role | What they receive |
|---|---|---|
| Aramchol 600mg | Experimental | One tablet of Aramchol 400 mg and one tablet of Aramchol 200 mg. Receives: Drug: Aramchol |
| Aramchol 400mg | Experimental | One tablet of Aramchol 400 mg and one tablet of matching placebo for Aramchol. Receives: Drug: Aramchol |
| Placebo | Placebo comparator | Two tablet of Aramchol matching placebo. Receives: Drug: Aramchol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Mean Liver Fat
absolute % change from baseline to end of study in liver triglycerides to water ratio (fat/water+fat) as measured by MRS
Measured: At screening (baseline) and at week 52
Secondary outcomes (3)
NASH Resolution Without Worsening of Fibrosis
The endpoint was defined as end of study biopsy, observed under microscope and showing:
- Cell Ballooning (special form of liver cell injury associated with cell swelling and enlargement)= 0
- Inflammation (presence or absence of cells from the immune system) = 0 or 1
- No worsening of fibrosis (scar formation) = increase in fibrosis score by 1 or more point
Measured: At screening and at week 52
Fibrosis Improvement Without Worsening of NASH
The endpoint was defined as end of study biopsy showing:
- A decrease in fibrosis score ≥ 1 point
- No worsening of NASH (defined by an increase of inflammation and/or ballooning)
Measured: At screening and at week 52
Change From Baseline to Week 52/Termination in ALT
Change from baseline to Week 52 or Termination visit in ALT levels (U/L)
Measured: At baseline until week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2014 (estimated)
- Study start29 Apr 2015
- Primary completion22 May 2018
- Study completion22 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Fatty LiverStudies 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 247 participants (actual)
Sponsor and investigators
- Lead sponsor
- Galmed Research and Development, Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Sharp, Diamond Pharma Services Regulatory Affairs Consultancy, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, ClinIntel, Itamar-Medical, Israel, One Way Liver OWL, Medical University of Graz, Tel-Aviv Sourasky Medical Center, DSG EDC, TransPerfect, Clinical Reference Laboratory
- Responsible party
- Sponsor
- Investigators
- Vlad Ratziu, MD, PhD, Principal investigator, Professor of Hepatology, Université Pierre et Marie Curie & Hospital Pitie Salpetriere Medical University, Paris.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02279524
- Sponsor's protocol ID
- Aramchol005
- Acronym
- Aramchol_005
- Status last verified
- Jun 2021
- First submitted
- 23 Oct 2014
- Last updated
- 14 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Ratziu V, de Guevara L, Safadi R, Poordad F, Fuster F, Flores-Figueroa J, Arrese M, Fracanzani AL, Ben Bashat D, Lackner K, Gorfine T, Kadosh S, Oren R, Halperin M, Hayardeny L, Loomba R, Friedman S; ARREST investigator study group; Sanyal AJ. Aramchol in patients with nonalcoholic steatohepatitis: a randomized, double-blind, placebo-controlled phase 2b trial. Nat Med. 2021 Oct;27(10):1825-1835. doi: 10.1038/s41591-021-01495-3. Epub 2021 Oct 7.
PubMed 34621052
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIb, Double Blind Randomized, Controlled Clinical Trial, to Evaluate the Efficacy and Safety of Two Aramchol Doses Versus Placebo in Patients With Non-Alcoholic Steatohepatitis (NASH) - Aramchol 005 Study
- ClinicalTrials.gov ID
- NCT02279524
- Acronym / sponsor ID
- Aramchol_005 / Aramchol005
- Keywords
- NASH, fibroses, obesity, diabetes
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 247 participants (actual)
- Lead sponsor
- Galmed Research and Development, Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Sharp, Diamond Pharma Services Regulatory Affairs Consultancy, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, ClinIntel, Itamar-Medical, Israel, One Way Liver OWL, Medical University of Graz, Tel-Aviv Sourasky Medical Center, DSG EDC, TransPerfect, Clinical Reference Laboratory
- Study start
- 29 Apr 2015 (actual)
- Primary completion
- 22 May 2018 (actual)
- Study completion
- 22 May 2018 (actual)
- First posted
- 31 Oct 2014 (estimated)
- Results
- Posted 14 Jul 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multicenter, Phase IIb, randomized, double blind, placebo-controlled study designed to evaluate the efficacy and safety of two Aramchol doses in subjects that are 18 to 75 years of age, with Non-Alcoholic Steatohepatitis (NASH) confirmed by liver biopsy performed in a period of 6 months before entering the study, with overweight or obesity and who are pre diabetic or type II diabetic.
Eligible subjects will be enrolled into three treatments arms: Aramchol 400 and 600 mg tablets and placebo tablets in ratio 2:2:1.
The subjects will be evaluated at study sites for 11 scheduled visits during one year (52 weeks). After completion of the study treatment period, the subjects will be followed for an additional period of 13 weeks without study medication (until visit 11 (week 65)).
Detailed description
This is a multicenter, Phase IIb, randomized, double blind, placebo-controlled study designed to evaluate the efficacy and safety of two Aramchol doses in subjects that are 18 to 75 years of age, with Non-Alcoholic Steatohepatitis (NASH) confirmed by liver biopsy performed in a period of 6 months before entering the study, with overweight or obesity and who are pre diabetic or type II diabetic.
Eligible subjects will be enrolled into three treatments arms: Aramchol 400 and 600 mg tablets and placebo tablets in ratio 2:2:1.
The subjects will be evaluated at study sites for 11 scheduled visits: at screening (visit 1(weeks -4 - 0)), baseline (visit 2 (day 0)), visit 3 (week 2), visit 4 week 4), visit 5 (week 8), visit 6 (week 12), visit 7 (week 24), visit 8 (week 32), visit 9 (week 40) and visit 10 (week 52 - (End of Treatment/early termination visit)). After completion of the study treatment period, the subjects will be followed for an additional period of 13 weeks without study medication (until visit 11 (week 65)).
During the screening period, the severity of the disease will be evaluated with blood tests, liver biopsy and NMRS.
During the study the following assessments will be performed:
- Vital signs will be measured at each study visit.
- A physical examination will be performed at the screening visit, 24 weeks, End of Treatment/early termination and week 65 visit.
The following blood tests will be performed: complete blood count (CBC), serum chemistry (including electrolytes, liver enzymes, direct and total bilirubin, glucose, lipid profile which include triglyceride, cholesterol, HDL, LDL and VLDL, CPK, creatinine, urea, albumin, alkaline phosphatase), ESR and urinalysis during the screening visit, baseline, week 2, 4, 8, 24, 40, 52 and 65 (end of follow up) visits. Serology (HBV, HCV and HIV) will be performed during the screening visit. Coagulation (fibrinogen, PT/INR, aPTT) will be measured during screening and at baseline, week 24, End of Treatment/early termination and week 65 visits. Insulin (HOMA) will be measured during the screening, at week 24 and End of Treatment/early termination visits. HbA1C will be measured during the screening, at week 8, 24, 40 and End of Treatment/early termination visits. C reactive protein, Leptin and Adiponectin will be measured during baseline visit and at end of treatment period. The blood samples taken at these visits, will be tested for possible biomarkers. TSH, T3 and T4 will be measured during the screening visit. beta-hCG in women of childbearing potential will be performed during the screening visit. A serum sample will be collected and kept frozen until study end in case special investigation needs to be performed. This sample will be collected during the screening and visit 10/Early Termination.
- Body weight and waist circumference will be measured in screening, baseline, week 24, end of treatment and week 65 visits. Height will be measured during the screening visit.
- ECG will be performed during the screening visit, visit 7 (week 24) and end of treatment visits.
- All subjects will undergo two NMRS scans, at screening and end of treatment visits.
- FibroMax test will be performed only if the investigator thinks it is necessary
- Liver biopsy will be conducted during the screening and end of treatment visit. The biopsy in the screening visit will be performed only if it was not done within the 6 months prior to this visit.
- Metabolomics blood test will be performed at the screening, visit 7 and the End-of-Treatment/Early Termination visits. From some consenting patients (about 15) a sample from the liver biopsy will be taken for analysis.
- Endothelial Function will be conducted in selected sites. The test will be conducted during the baseline visit before the study treatment will be given and End of Treatment/early termination visit.
- Blood sample for Aramchol trough level will be collected (pre-dose) from patients in Israel at baseline (visit 2) week 4 (visit 4), week 12 (visit 6), week 24 (visit 7), week 40 (visit 9), end of treatment (visit 10) and follow up (visit 11). At selected sites in Mexico, USA and Hong Kong one blood sample will be collected (pre-dose) on visit 4 (up to 10 subjects per country) to test for trough Aramchol blood level differences between populations (e.g., African American, Asian, Hispanic).
- Blood sample for gene analysis will be taken from all consenting patients during the baseline visit, will be kept frozen and analyzed only at the study end.
- Life style questionnaire will be completed at all visits.
- Adverse events will be monitored throughout the study.
- Concomitant Medications will be monitored throughout the study.
- Telephone contacts will be performed on week 16, 20, 28, 36, 44 and 48. An interim safety analysis will be conducted as soon as 120 subjects will completed the follow up period of 24 weeks under study treatment. An independent DSMB will analyze the safety data and recommend a continued course of action. All patients will continue to be treated under the study protocol until conclusion of the analysis will be known.
Safety assessment will include frequency and severity of treatment-emergent AEs, clinically significant laboratory abnormalities, ECG changes and physical examination findings.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Aramchol 600mg | Experimental | Drug: AramcholOne tablet of Aramchol 400 mg and one tablet of Aramchol 200 mg. |
| Aramchol 400mg | Experimental | Drug: AramcholOne tablet of Aramchol 400 mg and one tablet of matching placebo for Aramchol. |
| Placebo | Placebo comparator | Drug: AramcholTwo tablet of Aramchol matching placebo. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Male or female age 18 to 75 years.
- BMI between 25kg/m2 to 40kg/m2 or waist circumference between 88 cm to 200 cm for women, and between 102 cm to 200 cm for men. If there is deviation above the upper limit, please consult the MRI center, to ensure that the machine is suitable for the patient.
- Known type II Diabetes Mellitus or pre-Diabetes according to American Diabetes Association. One of the following 3 criteria is needed for pre-Diabetes: Fasting Plasma Glucose > 100mg/dl (5.5 mmol/l) or 2hPG following 75g OGTT > 140 (7.8 mmol/l) mg/dl or HbA1c > 5.7%. HbA1c can be repeated at Investigator's discretion.
- Histologically proven Steatohepatitis on a diagnostic liver biopsy performed either during screening or within 6 months before screening visit, confirmed by central laboratory reading of the slides.(Steatosis ≥1 + inflammation ≥1 + ballooning ≥1).Total activity NAS score of 4 or more.
- Liver fat concentration in the liver of 5.5% or more as measured by NMRS.
Key exclusion criteria (27 listed)
- Patients with other active (acute or chronic) liver disease other than NASH (e.g. viral hepatitis, unless eradicated at least 3 years prior to screening; genetic hemochromatosis; Wilson disease; alpha 1antitripsin deficiency; alcohol liver disease; drug-induced liver disease) at the time of randomization.
- Patients with clinically or histologically documented liver cirrhosis
- Known alcohol and/or any other drug abuse or dependence in the last five years.
- Known history or presence of clinically significant cardiovascular, gastrointestinal, metabolic other than Diabetes Mellitus, neurologic, pulmonary, endocrine, psychiatric, neoplastic disorder or nephrotic syndrome, that in the opinion of the Investigator warrant exclusion from the study.
- Patients with familial (i.e., genetic) hypertriglyceridemia and familial (i.e., genetic) hypercholesterolemia.
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 |
|---|---|---|
| AramcholAlso: PlaceboSubjects will be administered Aramchol as follows: * One tablet of Aramchol 400 mg and one tablet of matching placebo for Aramchol. * One tablet of Aramchol 400 mg and one tablet of Aramchol 200 mg. * Two tablet of Aramchol matching placebo. The tablets should be taken orally in the morning within 30 min after breakfast with a glass of water (250 ml). Subjects are allowed to omit study drugs up to 3 consecutive days during the study. | Drug | Aramchol 400mg, Aramchol 600mg, Placebo |
Primary outcome
Change From Baseline in Mean Liver Fat
Time frame: At screening (baseline) and at week 52
absolute % change from baseline to end of study in liver triglycerides to water ratio (fat/water+fat) as measured by MRS
3 secondary outcomes
NASH Resolution Without Worsening of Fibrosis
Time frame: At screening and at week 52
Fibrosis Improvement Without Worsening of NASH
Time frame: At screening and at week 52
Change From Baseline to Week 52/Termination in ALT
Time frame: At baseline until week 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34621052Ratziu V, de Guevara L, Safadi R, Poordad F, Fuster F, Flores-Figueroa J, Arrese M, Fracanzani AL, Ben Bashat D, Lackner K, Gorfine T, Kadosh S, Oren R, Halperin M, Hayardeny L, Loomba R, Friedman S; ARREST investigator study group; Sanyal AJ. Aramchol in patients with nonalcoholic steatohepatitis: a randomized, double-blind, placebo-controlled phase 2b trial. Nat Med. 2021 Oct;27(10):1825-1835. doi: 10.1038/s41591-021-01495-3. Epub 2021 Oct 7.
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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.
Vlad Ratziu, MD, PhD principal investigator
Professor of Hepatology, Université Pierre et Marie Curie & Hospital Pitie Salpetriere Medical University, Paris.
78 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Aramchol in people with Fatty Liver and Non-Alcoholic Steatohepatitis, run by Galmed Research and Development, Ltd. at 78 sites in 11 countries.
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 13 inclusion and 27 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: finished, as of the sponsor's last update on 14 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 78 sites in United States, Italy, Mexico, France, Israel and 6 more countries. 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?
Yes. Results are posted in the registry (first posted 14 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Mean Liver Fat (time frame: At screening (baseline) and at week 52). 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 NCT02279524, which also lists 1 linked publication.
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 14 Jul 2021.