Study Evaluating the Efficacy and Safety of Belapectin for the Prevention of Esophageal Varices in NASH Cirrhosis

NCT04365868 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: GT-031
• Study Type: interventional
• Target: 357
• Locations: 15 countries
• Sites: 156

Brief Summary

This seamless, adaptive, two-stage, Phase 2b/3, randomized, double-blind, multicenter, parallel-groups, placebo-controlled study will assess the efficacy, safety, and tolerability of belapectin compared with placebo in patients with nonalcoholic steatohepatitis (NASH) cirrhosis and clinical signs of portal hypertension but without esophageal varices at baseline.

Conditions

Prevention of Esophageal Varices; NASH - Nonalcoholic Steatohepatitis; Cirrhosis

Keywords

esophageal varices; belapectin; GR-MD-02; portal hypertension; nonalcoholic steatohepatitis (NASH) cirrhosis; NASH; cirrhosis

Outcome Measures

Primary Outcomes (1)

• Proportion of patients in the belapectin treatment groups who develop new esophageal varices at 78 weeks [18 months] of treatment compared to placebo

  Proportion of patients in the belapectin treatment groups who develop new esophageal varices at 78 weeks \[18 months\] of treatment compared to placebo

  At 78 weeks [18 months]

Secondary Outcomes (18)

• Efficacy: Cumulative incidence rate of patients in the belapectin treatment groups, compared to placebo, who develop varices (esophageal or gastric) requiring treatment

  Through study end, 78 weeks or 156 weeks

• Efficacy: Cumulative incidence rate of patients in the belapectin treatment groups, compared to placebo, who develop variceal bleed requiring hospitalization

  Through study end, 78 weeks or 156 weeks

• Efficacy: Cumulative incidence rate of patients in the belapectin treatment groups, compared to placebo, who develop clinically significant ascites requiring hospitalization

  Through study end, 78 weeks or 156 weeks

• Efficacy: Cumulative incidence rate of patients in the belapectin treatment groups, compared to placebo, who develop spontaneous bacterial peritonitis

  Through study end, 78 weeks or 156 weeks

• Efficacy: Cumulative incidence rate of patients in the belapectin treatment groups, compared to placebo, who develop hepatic encephalopathy (West Haven score ≥2 and requiring hospitalization)

  Through study end, 78 weeks or 156 weeks

Other Outcomes (3)

• Exploratory Efficacy:Change in liver stiffness measurement (LSM), baseline-adjusted, as determined by vibration controlled transient elastography (VCTE) (FibroScan) exams during Phase 2b and Phase 3

  Through study end, 78 weeks or 156 weeks

• Exploratory Efficacy: Difference in Chronic Liver Disease Questionnaire (CLDQ) scores between belapectin and placebo treatment during Phase 2b and Phase 3

  Through study end, 78 weeks or 156 weeks

• Safety: Incidence of adverse events

  Through study end, 78 weeks or 156 weeks

Study Arms (3)

belapectin 2 mg/kg lean body mass (LBM)

EXPERIMENTAL

Phase 2b: Belapectin 2 mg/kg lean body mass administered intravenously (IV) every other week for 78 weeks (18 months) Phase 3: The patient will be switched to the optimal dose

Drug: belapectin

belapectin 4 mg/kg lean body mass (LBM)

EXPERIMENTAL

Phase 2b: Belapectin 4 mg/kg lean body mass administered intravenously (IV) every other week for 78 weeks (18 months) Phase 3: The patient will be switched to the optimal dose

Drug: belapectin

Placebo

PLACEBO COMPARATOR

Phase 2b: Placebo, administered intravenously (IV) every other week for 78 weeks (18 months) Phase 3:Placebo, administered intravenously (IV) every other week for 78 weeks (18 months)

Drug: Placebo

Interventions

belapectin DRUG

intravenous

Also known as: GR-MD-02, galactoarabino rhamnogalacturonate

belapectin 2 mg/kg lean body mass (LBM); belapectin 4 mg/kg lean body mass (LBM)

Placebo DRUG

intravenous

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:

• Each subject must meet all of the following criteria to be enrolled in this study:
• Is male or female, ≥ 18 and ≤ 75 years of age at the time of Screening.
• Is willing and able to provide written informed consent prior to the initiation of any study-specific procedures.
• Has evidence of portal hypertension, with either one of the following:
• platelet count \<150,000/mm3
• documented hepatic venous pressure gradient (HVPG) measurement \>6 mmHg
• at least two of the following:
• spleen size ≥14 cm (documented by ultrasound, MRI, or CT scan)
• abdominal collateral circulation (documented by ultrasound, MRI, or CT scan or physical examination, ie, caput medusae)
• documented liver transient elastography (eg, FibroScan) ≥20 kilopascals (kPa).
• aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \>1.
• Has a history confirming nonalcoholic steatohepatitis (NASH) cirrhosis, with at least one of the following:
• There is a historical liver biopsy showing cirrhosis with steatohepatitis. There is no evidence for a competing etiology for the cirrhosis.
• There is a historical liver biopsy showing steatohepatitis, and there is evidence of cirrhosis from clinical or imaging data or a second liver biopsy showing cirrhosis without all features of NASH (as the histological NASH lesions may have burnt out). There is no evidence for a competing etiology. There is at least 1 co-existing metabolic comorbidity at Screening: obesity (with either body mass index \[BMI\] ≥30 kg/m2 or waist circumference ≥102 cm \[40 in, men\] or ≥88 cm \[35 in, women\], or by ethnically appropriate cutpoints); hypertension (either on anti hypertensive drug therapy for at least 1 year or systolic/diastolic blood pressure (BP) \>140/80 mm Hg); Type 2 diabetes (glycated hemoglobin \[HbA1c\] ≥6.5%, or on anti-diabetic medication for at least 1 year); or dyslipidemia (triglycerides ≥150 mg/dL or on drug therapy for hypertriglyceridemia for at least 6 months; high-density lipoprotein cholesterol ≤40 mg/dL \[men\] or ≤50 mg/dL \[women\]) to corroborate a diagnosis of nonalcoholic fatty liver disease (NAFLD).
• There is a historical liver biopsy showing cirrhosis with steatosis but not steatohepatitis. There is no evidence for a competing etiology. There are at least 2 co-existing (or history of) metabolic comorbidities (with obesity or diabetes being one of them) to corroborate a diagnosis of NAFLD.

You may not qualify if:

• Subjects meeting any of the following criteria will be excluded from the study:
• Presence of esophageal, gastroesophageal, or isolated gastric varices, based on an upper gastrointestinal (GI) esophagogastroduodenoscopy (EGD) exam conducted during Screening. Patients with portal hypertensive gastropathy could be enrolled.
• History of hepatic cirrhosis decompensation including any episode of variceal bleeding, ascites not controlled by medication, spontaneous bacterial peritonitis or overt hepatic encephalopathy (West Haven grade ≥2 as assessed by the principal investigator), OR develops signs of hepatic cirrhosis decompensation during Screening.
• Known or suspected abuse of alcohol (\>20 g/day for women or \>30 g/day for men \[on average per day\]), as per medical history. Significant alcohol consumption is defined as more than 20 grams per day in females and more than 30 grams per day in males. On average, a standard drink in the United States is considered to be 14 grams of alcohol, equivalent to 12 fluid ounces of regular beer (5% alcohol), 5 fluid ounces of table wine (12% alcohol), or 1.5 fluid ounces of 80 proof spirits (40% alcohol).
• Alcohol dependence (ie, a score \>8 on the Alcohol Use Disorders Identification Test)
• Narcotics or any other drug abuse or dependence in the last 5 years
• Prior trans-jugular intrahepatic portal-systemic (TIPS) shunt procedure
• Documented causes of liver disease other than NASH, including but not restricted to:
• Viral hepatitis, unless eradicated at least 3 years prior to Screening
• acute hepatitis A infection (presence of hepatitis A immunoglobulin M \[IgM\] at Screening)
• positive hepatitis B surface antigen
• positive hepatitis C virus (HCV) ribonucleic acid (to be performed prior to randomization in case of positive HCV antibody)
• Documented drug-induced liver disease
• Alcoholic liver disease
• Autoimmune hepatitis

Sponsors & Collaborators

• Galectin Therapeutics Inc.: lead

Study Sites (156)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Digestive Health Specialists

Dothan, Alabama, 36305, United States

Location

The Institute for Liver Health

Chandler, Arizona, 85224, United States

Location

Arizona Liver Health - Glendale

Glendale, Arizona, 85306, United States

Location

Institute for Liver Health - Tucson

Tucson, Arizona, 85712, United States

Location

Liver Wellness Center - Little Rock

Little Rock, Arkansas, 72205-6414, United States

Location

Hope Clinical Research, Inc.

Canoga Park, California, 91303, United States

Location

Southern California GI & Liver Centers

Coronado, California, 92118, United States

Location

University of California San Diego Medical Center -La Jolla Multi-Specialty Clinics- Perlman Offices

La Jolla, California, 92037, United States

Location

Om Research LLC

Lancaster, California, 93534, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

inSite Digestive Health Care - Orange

Orange, California, 92868, United States

Location

California Liver Research Institute

Pasadena, California, 91105, United States

Location

Inland Empire Liver Foundation

Rialto, California, 92377, United States

Location

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Peak Gastroenterology Associates

Colorado Springs, Colorado, 80907-6262, United States

Location

Integrity Clinical Research, LLC (ICR SITES) - Doral

Doral, Florida, 33166, United States

Location

Nature Coast Clinical Research, LLC

Inverness, Florida, 34452, United States

Location

Mayo Clinic Hospital - Florida

Jacksonville, Florida, 32224-1865, United States

Location

Florida Research Institute

Lakewood Rch, Florida, 34211, United States

Location

ClinCloud LLC

Maitland, Florida, 32751-3320, United States

Location

Advanced Pharma CR, LLC

Miami, Florida, 33147, United States

Location

Genoma Research Group, Inc.

Miami, Florida, 33165, United States

Location

Sensible Healthcare

Ocoee, Florida, 34761, United States

Location

Guardian Angel Health Services, Inc.

Tampa, Florida, 33614, United States

Location

Florida Medical Center & Research

Zephyrhills, Florida, 33542, United States

Location

Digestive Healthcare of Georgia, P.C.

Atlanta, Georgia, 30309, United States

Location

Gastroenterology Associates of Central Georgia, LLC

Macon, Georgia, 31201, United States

Location

Gastrointestinal Specialists of Georgia, PC

Marietta, Georgia, 30060, United States

Location

Loyola University Health System

Maywood, Illinois, 60153, United States

Location

IU Health University Hospital

Indianapolis, Indiana, 46202, United States

Location

Michiana Gastroenterology, Inc.

South Bend, Indiana, 46635, United States

Location

Kansas Medical Clinic PA

Topeka, Kansas, 66606, United States

Location

University of Louisville Physicians - Cardiovascular Medicine Physicians Outpatient Center

Louisville, Kentucky, 40202-2046, United States

Location

Tandem Clinical Research, LLC

Marrero, Louisiana, 70072, United States

Location

Tulane Cancer Center

New Orleans, Louisiana, 70112-2600, United States

Location

Mercy Medical Center - The Institute for Digestive Health and Liver Disease

Baltimore, Maryland, 21202, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111-1552, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Henry Ford Health System - Hemophilia and Thrombosis Treatment Center

Detroit, Michigan, 48202, United States

Location

Gastroenterology Associates of Western Michigan

Wyoming, Michigan, 49519, United States

Location

Southern Therapy and Advanced Research (STAR) - Jackson

Jackson, Mississippi, 39216, United States

Location

Kansas City Research Institute

Kansas City, Missouri, 64131, United States

Location

Excel Clinical Research - Las Vegas

Las Vegas, Nevada, 89109-6209, United States

Location

Mount Sinai Beth Israel

New York, New York, 10003, United States

Location

NYU Langone Medical Center

New York, New York, 10016-6402, United States

Location

NewYork-Presbyterian Hospital/Weill Cornell Medical Center

New York, New York, 10021, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

UNC-Chapel Hill School of Medicine

Chapel Hill, North Carolina, 273302, United States

Location

Cumberland Research Associates, LLC

Fayetteville, North Carolina, 28304-3571, United States

Location

Lucas Research

Morehead City, North Carolina, 28557, United States

Location

Consultants for Clinical Research

Cincinnati, Ohio, 45249, United States

Location

University of Cincinnati Physicians Company, LLC

Cincinnati, Ohio, 45267-0595, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44016, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

The Jefferson Digestive Health Institute - Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pittsburgh Medical Center (UPMC) - The Center for Liver Diseases

Pittsburgh, Pennsylvania, 15213, United States

Location

Medical University of South Carolina (MUSC)

Charleston, South Carolina, 29425, United States

Location

Galen Medical Group - Ziegler Plaza

Chattanooga, Tennessee, 37343-5470, United States

Location

University Diabetes & Endocrine Consultants

Chattanooga, Tennessee, 37411, United States

Location

Gastro One - GI Diagnostic and Therapeutic Endoscopy Center - 1310 Wolf Park

Germantown, Tennessee, 38138, United States

Location

Associates in Gastroenterology

Hermitage, Tennessee, 37067, United States

Location

East Tennessee Research Institute - Gastrointestinal Associates of Northeast Tennessee, P.C.

Johnson City, Tennessee, 37604-6063, United States

Location

Texas Clinical Research Institute, LLC

Arlington, Texas, 76012, United States

Location

Liver Specialists of Texas

Austin, Texas, 78757, United States

Location

Methodist Transplant Physicians

Dallas, Texas, 75203, United States

Location

Texoma Liver Center PLLC. - Denison

Denison, Texas, 75020, United States

Location

South Texas Research Institute

Edinburg, Texas, 78539, United States

Location

Baylor College of Medicine - Baylor Clinic - Abdominal Transplant & Liver Disease Clinic

Houston, Texas, 77030, United States

Location

Pioneer Research Solutions Inc - Houston - Stancliff Rd

Houston, Texas, 77099, United States

Location

The Texas Liver Institute, Inc.

San Antonio, Texas, 78215, United States

Location

Pinnacle Clinical Research

San Antonio, Texas, 78229, United States

Location

Impact Research Institute

Waco, Texas, 76710-2582, United States

Location

University of Utah Health Care - UUHC - Kidney & Liver Clinic

Salt Lake City, Utah, 84132-0001, United States

Location

University of Virginia School of Medicine

Charlottesville, Virginia, 22908, United States

Location

Gastroenterology Associates of Fredericksburg

Fredericksburg, Virginia, 22401-8425, United States

Location

Bon Secours Liver Institute of Virginia - Newport News

Newport News, Virginia, 23602, United States

Location

Bon Secours Liver Institute of Virginia - Richmond

Richmond, Virginia, 23226, United States

Location

Hunter Holmes McGuire VA Medical Center

Richmond, Virginia, 23249-0001, United States

Location

Velocity Clinical Research, Spokane

Spokane, Washington, 99202-3462, United States

Location

Hospital Italiano de Buenos Aires

Buenos Aires, ARG, C1181ACH, Argentina

Location

Hospital Británico de Buenos Aires

Buenos Aires, ARG, C1280AEB, Argentina

Location

Centro de Investigaciones Metabólicas (CINME)

Capital Federal, ARG, C1056ABJ, Argentina

Location

Nepean Hospital

Kingswood, New South Wales, 2750, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Box Hill Hospital

Box Hill, Victoria, 3128, Australia

Location

Monash Medical Centre Clayton

Clayton, Victoria, 3168, Australia

Location

Fiona Stanley Hospital

Murdoch, Western Australia, 6150, Australia

Location

Antwerp University Hospital

Edegem, Antwerpen, 2650, Belgium

Location

Clinique Universitaire De Bruxelles Hôpital Erasme VZW

Brussels, BEL, 1070, Belgium

Location

AZ Maria Middelares

Ghent, VOV, 9000, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, VOV, 9000, Belgium

Location

Groupe sante CHC - Clinique du MontLegia

Liège, WLG, 4000, Belgium

Location

University of Calgary - Heritage Medical Research Clinic - Foothills Hospital Center

Calgary, Alberta, T2N 4Z6, Canada

Location

Pacific Gastroenterology Associates

Vancouver, British Columbia, V6Z 2K5, Canada

Location

Brampton Civic Hospital

Brampton, Ontario, L6R 3J7, Canada

Location

Toronto Liver Centre

Toronto, Ontario, M6H 3M1, Canada

Location

Centre Hospitalier de l'Université de Montréal (CHUM)

Montreal, Quebec, H2X 0A9, Canada

Location

Hospital de La Serena

La Serena, CHL, 1710216, Chile

Location

Clínica Universidad de los Andes

Santiago, CHL, 7550000, Chile

Location

Centro de Investigaciones Clinicas Vina del Mar

Viña del Mar, CHL, 07081-2221, Chile

Location

Hospital Clínico Universidad de Chile

Santiago, 8380000, Chile

Location

Centre Hospitalier Universitaire d'Amiens

Amiens, 80054, France

Location

Hôpital Avicenne

Bobigny, 93000, France

Location

CHU Hôpital Henri Mondor

Créteil, 94000, France

Location

CHU de Grenoble

Grenoble, 38043, France

Location

Hôpital de la Croix-Rousse

Lyon, 69004, France

Location

CHRU Montpellier - Saint Eloi

Montpellier, 34090, France

Location

CHU Nancy - Hôpital Brabois

Nancy, 54511, France

Location

CHU de Nice - L'Archet

Nice, 6202, France

Location

Hôpital Cochin

Paris, 75014, France

Location

Hôpitaux Universitaires de Strasbourg - Hôpital Civil

Strasbourg, 67091, France

Location

Universitatsmedizin der Johannes Gutenberg-Universitat Mainz

Mainz, Rhineland-Palatinate, 55131, Germany

Location

EUGASTRO GmbH

Leipzig, Saxony, 4103, Germany

Location

Goethe-Universität Frankfurt am Main

Frankfurt am Main, 60590, Germany

Location

Soroka Medical Center

Beersheba, 84101, Israel

Location

Rambam Medical Center

Haifa, 3109601, Israel

Location

Carmel Medical Center

Haifa, 34362, Israel

Location

Hadassah Ein Karem Hospital

Jerusalem, 91120, Israel

Location

Holy Family Hospital

Nazareth, 16100, Israel

Location

Rabin Medical Center - Beilinson Hospital

Petah Tikva, 4941492, Israel

Location

The Chaim Sheba Medical Center - The Center for Liver Diseases

Ramat Gan, 52621, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

CICPA Centro de Investigación Clinica del Pacifico

Acapulco de Juárez, Guerrero, 39670, Mexico

Location

Centro de Investigacion Medico Biologica y Terapia Avanzada SC

Guadalajara, Jalisco, 44130, Mexico

Location

Investigacion Biomedica para el desarrollo de farmacos SA de CV

Zapopan, Jalisco, 45070, Mexico

Location

Investigacion Biomedica para el desarrollo de farmacos SA de CV

Benito Juárez, Mexico City, 03103, Mexico

Location

CEMDEC SA de CV Centro Mexicano de Desarrollo de Estudios Clinicos

Cuauhtémoc, Mexico City, 06100, Mexico

Location

Centro Especializado en Diabetes, Obesidad y Pevencion de enfermedades Cadiovasculares SC.

Miguel Hidalgo, Mexico City, 11650, Mexico

Location

Hospital Universitario Dr. Jose Eleuterio Gonzalez Servicio de Gastroenterología

Monterrey, Nuevo León, 64460, Mexico

Location

Oaxaca Site Management Organization SC.

Oaxaca City, Oaxaca, 68000, Mexico

Location

Consultorio Medico

Ciudad de Mexico, State of Mexico, 6700, Mexico

Location

Medical Care and Research SA de CV

Mérida, Yucatán, 97070, Mexico

Location

Centro de Investigación Medica de Aguascalientes

Aguascalientes, 20116, Mexico

Location

MEDIVEST Centro de Investigacion integral

Chihuahua City, 31203, Mexico

Location

Centro de Investigacion Clinica de Oaxaca

Oaxaca City, 68020, Mexico

Location

SP CSK im Prof. Kornela Gibińskiego Śląskiego Uniwersytetu Medycznego w Katowicach

Katowice, Silesian Voivodeship, 40-752, Poland

Location

ID Clinic

Mysłowice, Silesian Voivodeship, 41-400, Poland

Location

Medyczny Katedra i Klinika Chorób Zakaźnych, Chorób Wątroby i Nabytych Niedoborów Odpornościowych

Wroclaw, 50-220, Poland

Location

Medical University of Lodz

Lodz, Łódź Voivodeship, 91-347, Poland

Location

Fundacion de Investigacion de Diego

San Juan, 00927, Puerto Rico

Location

Hanyang University Seoul Hospital

Seoul, KOR, 4763, South Korea

Location

Yonsei University, Wonju Severance Christian Hospital

Seoul, KOR, 8308, South Korea

Location

Yonsei University, Wonju Severance Christian Hospital

Wŏnju, KOR, 26426, South Korea

Location

Digestive Research Alliance of Michiana, LLC

Incheon, 400-711, South Korea

Location

Hospital Universitario 12 de Octubre

Madrid, ESP, 28041, Spain

Location

Hospital del Mar Research Institute

Barcelona, 8003, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Puerta de Hierro - Majadahonda

Majadahonda, 28222, Spain

Location

Complexo Hospitalario Universitario de Pontevedra

Pontevedra, 36071, Spain

Location

Hospital Universitario Marqués de Valdecilla

Santander, 39008, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

King's College Hospital NHS Foundation Trust

London, GBR, SE5 9RS, United Kingdom

Location

The University of Nottingham - Nottingham Digestive Diseases Centre Biomedical Research Unit

Nottingham, NGM, NG7 2UH, United Kingdom

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Fibrosis; Esophageal and Gastric Varices; Hypertension, Portal

Interventions

belapectin

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Esophageal Diseases; Gastrointestinal Diseases

Study Officials

• Khurram Jamil, M.D.

  Galectin Therapeutics Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2020
• First Posted: April 28, 2020
• Study Start: June 25, 2020
• Primary Completion: March 11, 2025
• Study Completion: April 10, 2025
• Last Updated: February 20, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (5); ES (8); AR (3); IL (8); GB (2); US (81); PR (1); ME (13); PL (4); FR (10); BE (5); AU (5); KR (4); CL (4); DE (3)