A Clinical Trial to Evaluate the Efficacy and Safety of Two Aramchol Doses Versus Placebo in Patients With NASH

NCT02279524 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: Aramchol005
• Study Type: interventional
• Target: 247
• Locations: 11 countries
• Sites: 78

Brief 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 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)).

Conditions

Fatty Liver; Non-Alcoholic Steatohepatitis; Liver Diseases; Liver Fibroses

Keywords

NASH; fibroses; obesity; diabetes

Outcome Measures

Primary Outcomes (1)

• 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

  At screening (baseline) and at week 52

Secondary Outcomes (3)

• NASH Resolution Without Worsening of Fibrosis

  At screening and at week 52

• Fibrosis Improvement Without Worsening of NASH

  At screening and at week 52

• Change From Baseline to Week 52/Termination in ALT

  At baseline until week 52

Other Outcomes (1)

• Change From Baseline to Termination/Early Termination in HbA1C

  At baseline until week 52

Study Arms (3)

Aramchol 600mg

EXPERIMENTAL

One tablet of Aramchol 400 mg and one tablet of Aramchol 200 mg.

Drug: Aramchol

Aramchol 400mg

EXPERIMENTAL

One tablet of Aramchol 400 mg and one tablet of matching placebo for Aramchol.

Drug: Aramchol

Placebo

PLACEBO COMPARATOR

Two tablet of Aramchol matching placebo.

Drug: Aramchol

Interventions

Aramchol DRUG

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.

Also known as: Placebo

Aramchol 400mg; Aramchol 600mg; Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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).

You may not qualify if:

• 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.
• 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
• 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:

Sponsors & Collaborators

• Galmed Research and Development, Ltd.: lead
• Sharp: collaborator
• Diamond Pharma Services Regulatory Affairs Consultancy: collaborator
• Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico: collaborator
• ClinIntel: collaborator
• Itamar-Medical, Israel: collaborator
• One Way Liver OWL: collaborator
• Medical University of Graz: collaborator
• Tel-Aviv Sourasky Medical Center: collaborator
• DSG EDC: collaborator
• TransPerfect: collaborator
• Clinical Reference Laboratory: collaborator

Study Sites (78)

Profil Institue for Clinical Research Inc.

Chula Vista, California, 91911, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

California Liver Research Institute

Pasadena, California, 91105, United States

Location

Inland Empoire Liver Foundation

Rialto, California, 92377, United States

Location

University of California Department of Medicine Division of Gastroenterology

San Diego, California, 92103, United States

Location

Orange County Research Center

Tustin, California, 92780, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Mount Sinai

New York, New York, 10029, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Wake Research

Raleigh, North Carolina, 27612, United States

Location

Texas Digestive Disease Consultants

Dallas, Texas, 75246, United States

Location

Brooke Army Medical Center

Fort Sam Houston, Texas, 78234, United States

Location

Gastroenterology Consultants of San Antonio

Live Oak, Texas, 78233, United States

Location

Texas Liver Institute San Antonio

San Antonio, Texas, 78215, United States

Location

Clinical Trials of Texas

San Antonio, Texas, 78229, United States

Location

University of Virginia Medical Center

Charlottesville, Virginia, 22908, United States

Location

Biomedica Research Group

Santiago, Chile

Location

Centro de Investigacion Clinica CEIC

Santiago, Chile

Location

Hospital Clinico Universidad de Chile

Santiago, Chile

Location

Pontificia Universidad Catolica de Chile

Santiago, Chile

Location

Centro de Investigaciones Clinicas Vina del Mar

Viña del Mar, Chile

Location

Centre Hospitalier Universitaire (CHU) d'Angers

Angers, France

Location

Centre Hospitalier Universitaire Dijon Bourgogne

Dijon, France

Location

San Joseph Service Hepato Gastro Entrologie

Marseille, France

Location

Hospital Saint Eloi

Montpellier, France

Location

CHU Centre Hospiatalier Universitaire de Rennes

Paris, France

Location

Hospital Pitie-Salpetriere

Paris, France

Location

Hospital Saint-Antoine AP-HP

Paris, France

Location

Hopital Paul Brousse

Villejuif, France

Location

Unimed Adjara

Batumi, Georgia

Location

Clinic Cortex

Tbilisi, Georgia

Location

David Tatishvili Medical Center

Tbilisi, Georgia

Location

LTD Diacor

Tbilisi, Georgia

Location

Research Institute of Clinical Medicine

Tbilisi, Georgia

Location

Medizinische Hochschule

Hanover, Germany

Location

EUGASTRO GmbH

Leipzig, Germany

Location

Universitat Leipzig Medizinische Fakultat

Leipzig, Germany

Location

Humanity & Health Medical Centre

Central, Hong Kong

Location

Carmel Medical Center

Haifa, Israel

Location

Rambam Medical Center

Haifa, Israel

Location

Hadassah Ein Karem Medical Cente

Jerusalem, Israel

Location

Naharia Medical Center

Nahariya, Israel

Location

The Holy family Medical Center

Nazareth, Israel

Location

Sheba Medical Center

Ramat Gan, Israel

Location

Tel-Aviv Saurasky Medical Center

Tel Aviv, Israel

Location

Asaf Harofeh Medical Center

Zrifin, Israel

Location

Spedali Civili di Brescia

Brescia, Italy

Location

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, Italy

Location

A.O. San Paolo

Milan, Italy

Location

A.O. U. "Federico II" di Napoli

Napoli, Italy

Location

Azienda Ospedaliera di Rilievo Nazionale "A.Cardarelli"

Napoli, Italy

Location

Azienda Ospidaliera Universitaria Seconda Universita di Napoli

Napoli, Italy

Location

A.O.U. Maggiore della Carità

Novara, Italy

Location

"Ospedale Cristo Re" dell'Istituto Figlie di N.S. al Monte Calvario

Roma, Italy

Location

Fondazione Policlinico di Tor Vergata

Roma, Italy

Location

Ospedale San Camillo

Roma, Italy

Location

Policlinico A. Gemelli

Roma, Italy

Location

Policlinico Umberto I Di Roma

Roma, Italy

Location

Policlinico Univestitario Campus Biomedico

Roma, Italy

Location

Hospital of Lithuanian University of Health Sciences Kaunas Clinics

Kaunas, Lithuania

Location

Klaipeda University Hospital

Klaipėda, Lithuania

Location

Vilinius University Hospital Santariskiu Klinikos

Vilnius, Lithuania

Location

Unidad de Hígado Hospital Universitario Dr. José Eleuterio González

Monterrey, Nuevo León, Mexico

Location

JM Research

Cuernavaca, Mexico

Location

Consultorio Médico

Metepec, Mexico

Location

Torre de Consultorios Clinica Londres

Mexico City, 06700, Mexico

Location

Consultorio Medico del Dr. Mauricio Castillo Barradas

Mexico City, Mexico

Location

Consultorio Medico

Mexico City, Mexico

Location

Instituto de Ciencias Medicas y de la Nutricion Salvador Zubiran

Mexico City, Mexico

Location

Torre de Consultorios Clinica Londres

Mexico City, Mexico

Location

Accelerium Clinical Research

Monterrey, Mexico

Location

"Angeles Valle oriente" Hospital

San Pedro Garza García, Mexico

Location

Clinical Institute Colentina

Bucharest, Romania

Location

The National Institute for Infectious Diseases "Prof. Dr. Matei Bals", Clinical Department for Adults II

Bucharest, Romania

Location

Cluj County Emergency Hospital

Cluj-Napoca, 400013, Romania

Location

TVM Medical

Cluj-Napoca, 400013, Romania

Location

County Hospital Mures-Gastroenterology Department

Târgu Mureş, Romania

Location

Related Publications (1)

• 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.

  PMID: 34621052 DERIVED

MeSH Terms

Conditions

Fatty Liver; Non-alcoholic Fatty Liver Disease; Liver Diseases; Liver Cirrhosis; Fibrosis; Obesity; Diabetes Mellitus

Interventions

aramchol

Condition Hierarchy (Ancestors)

Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Medical Director
• Organization: Galmed Research and Development, Ltd.

clinicaltrial@galmedpharma.com

+972.3.693.8448

Study Officials

• Vlad Ratziu, MD, PhD

  Professor of Hepatology, Université Pierre et Marie Curie & Hospital Pitie Salpetriere Medical University, Paris.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2014
• First Posted: October 31, 2014
• Study Start: April 29, 2015
• Primary Completion: May 22, 2018
• Study Completion: May 22, 2018
• Last Updated: July 14, 2021
• Results First Posted: July 14, 2021

Record last verified: 2021-06

Locations

LI (3); DE (3); US (17); GE (5); CL (5); IL (8); FR (8); IT (13); ME (10); RO (5); HK (1)