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

A Seamless, Adaptive, Phase 2b/3, Double-Blind, Randomized, Placebo-controlled, Multicenter, International Study Evaluating the Efficacy and Safety of Belapectin (GR MD-02) for the Prevention of Esophageal Varices in NASH Cirrhosis

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.

Study Overview

• Status: Terminated
• Conditions: Cirrhosis; NASH - Nonalcoholic Steatohepatitis; Prevention of Esophageal Varices
• Intervention / Treatment: Drug: belapectin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 357
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Argentina
  • ARG
    • Buenos Aires, ARG, Argentina, C1280AEB
      • Hospital Britanico de Buenos Aires
    • Buenos Aires, ARG, Argentina, C1181ACH
      • Hospital Italiano de Buenos Aires
    • Capital Federal, ARG, Argentina, C1056ABJ
      • Centro de Investigaciones Metabolicas (CINME)
• Australia
  • New South Wales
    • Kingswood, New South Wales, Australia, 2750
      • Nepean Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Box Hill Hospital
    • Clayton, Victoria, Australia, 3168
      • Monash Medical Centre Clayton
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Fiona Stanley Hospital
• Belgium
  • Antwerpen
    • Edegem, Antwerpen, Belgium, 2650
      • Antwerp University Hospital
  • BEL
    • Brussels, BEL, Belgium, 1070
      • Clinique Universitaire De Bruxelles Hôpital Erasme VZW
  • VOV
    • Ghent, VOV, Belgium, 9000
      • AZ Maria Middelares
    • Ghent, VOV, Belgium, 9000
      • Universitair Ziekenhuis Gent
  • WLG
    • Liège, WLG, Belgium, 4000
      • Groupe sante CHC - Clinique du MontLegia
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • University of Calgary - Heritage Medical Research Clinic - Foothills Hospital Center
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 2K5
      • Pacific Gastroenterology Associates
  • Ontario
    • Brampton, Ontario, Canada, L6R 3J7
      • Brampton Civic Hospital
    • Toronto, Ontario, Canada, M6H 3M1
      • Toronto Liver Centre
  • Quebec
    • Montreal, Quebec, Canada, H2X 0A9
      • Centre Hospitalier de l'Université de Montréal (CHUM)
• Chile
  • Santiago, Chile, 8380000
    • Hospital Clínico Universidad de Chile
  • CHL
    • La Serena, CHL, Chile, 1710216
      • Hospital de La Serena
    • Santiago, CHL, Chile, 7550000
      • Clínica Universidad de los Andes
    • Viña del Mar, CHL, Chile, 07081-2221
      • Centro de Investigaciones Clinicas Viña del Mar
• France
  • France
    • Amiens, France, France, 80054
      • Centre Hospitalier Universitaire D'Amiens
    • Bobigny, France, France, 93000
      • Hopital Avicenne
    • Créteil, France, France, 94000
      • CHU Hôpital Henri Mondor
    • Grenoble, France, France, 38043
      • CHU de Grenoble
    • Lyon, France, France, 69004
      • Hopital De La Croix-Rousse
    • Montpellier, France, France, 34090
      • CHRU Montpellier - Saint Eloi
    • Nancy, France, France, 54511
      • CHU Nancy - Hôpital Brabois
    • Nice, France, France, 6202
      • CHU de Nice - L'Archet
    • Paris, France, France, 75014
      • Hôpital Cochin
    • Strasbourg, France, France, 67091
      • Hôpitaux Universitaires de Strasbourg - Hôpital Civil
• Germany
  • Germany
    • Frankfurt am Main, Germany, Germany, 60590
      • Goethe-Universität Frankfurt am Main
  • Rhineland-Palatinate
    • Mainz, Rhineland-Palatinate, Germany, 55131
      • Universitätsmedizin der Johannes Gutenberg-Universität Mainz
  • Saxony
    • Leipzig, Saxony, Germany, 4103
      • EUGASTRO GmbH
• Israel
  • Beersheba, Israel, 84101
    • Soroka Medical Center
  • Haifa, Israel, 3109601
    • Rambam Medical Center
  • Haifa, Israel, 34362
    • Carmel Medical Center
  • Jerusalem, Israel, 91120
    • Hadassah Ein Karem Hospital
  • Nazareth, Israel, 16100
    • Holy Family Hospital
  • Petah Tikva, Israel, 4941492
    • Rabin Medical Center - Beilinson Hospital
  • Ramat Gan, Israel, 52621
    • The Chaim Sheba Medical Center - The Center for Liver Diseases
  • Tel Aviv, Israel, 64239
    • Tel Aviv Sourasky Medical Center
• Mexico
  • Aguascalientes
    • Aguascalientes, Aguascalientes, Mexico, 20116
      • Centro de Investigación Médica de Aguascalientes
  • Chihuahua
    • Chihuahua City, Chihuahua, Mexico, 31203
      • MEDIVEST Centro de Investigacion integral
  • Guerrero
    • Acapulco de Juárez, Guerrero, Mexico, 39670
      • CICPA Centro de Investigación Clinica del Pacifico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44130
      • Centro de Investigacion Medico Biologica y Terapia Avanzada SC
    • Zapopan, Jalisco, Mexico, 45070
      • Investigacion Biomedica para el desarrollo de farmacos SA de CV
  • Mexico City
    • Benito Juárez, Mexico City, Mexico, 03103
      • Investigacion Biomedica para el desarrollo de farmacos SA de CV
    • Cuauhtémoc, Mexico City, Mexico, 06100
      • CEMDEC SA de CV Centro Mexicano de Desarrollo de Estudios Clinicos
    • Miguel Hidalgo, Mexico City, Mexico, 11650
      • Centro Especializado en Diabetes, Obesidad y Pevencion de enfermedades Cadiovasculares SC.
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64460
      • Hospital Universitario Dr. Jose Eleuterio Gonzalez Servicio de Gastroenterología
  • Oaxaca
    • Oaxaca City, Oaxaca, Mexico, 68020
      • Centro de Investigacion Clinica de Oaxaca
    • Oaxaca City, Oaxaca, Mexico, 68000
      • Oaxaca Site Management Organization SC.
  • State of Mexico
    • Ciudad de Mexico, State of Mexico, Mexico, 6700
      • Consultorio Medico
  • Yucatán
    • Mérida, Yucatán, Mexico, 97070
      • Medical Care and Research SA de CV
• Poland
  • Poland
    • Wroclaw, Poland, Poland, 50-220
      • Medyczny Katedra i Klinika Chorób Zakaźnych, Chorób Wątroby i Nabytych Niedoborów Odpornościowych
  • Silesian Voivodeship
    • Katowice, Silesian Voivodeship, Poland, 40-752
      • SP CSK im Prof. Kornela Gibińskiego Śląskiego Uniwersytetu Medycznego w Katowicach
    • Mysłowice, Silesian Voivodeship, Poland, 41-400
      • ID Clinic
  • Łódź Voivodeship
    • Lodz, Łódź Voivodeship, Poland, 91-347
      • Medical University of Lodz
• Puerto Rico
  • Puerto Rico
    • San Juan, Puerto Rico, Puerto Rico, 00927
      • Fundacion De Investigacion de Diego
• South Korea
  • Incheon, South Korea, 400-711
    • Digestive Research Alliance of Michiana, LLC
  • KOR
    • Seoul, KOR, South Korea, 4763
      • Hanyang University Seoul Hospital
    • Seoul, KOR, South Korea, 8308
      • Yonsei University, Wonju Severance Christian Hospital
    • Wŏnju, KOR, South Korea, 26426
      • Yonsei University, Wonju Severance Christian Hospital
• Spain
  • ESP
    • Madrid, ESP, Spain, 28041
      • Hospital Universitario 12 de Octubre
  • Spain
    • Barcelona, Spain, Spain, 8003
      • Hospital del Mar Research Institute
    • Madrid, Spain, Spain, 28034
      • Hospital Universitario Ramón y Cajal
    • Madrid, Spain, Spain, 28046
      • Hospital Universitario La Paz
    • Majadahonda, Spain, Spain, 28222
      • Hospital Universitario Puerta de Hierro - Majadahonda
    • Pontevedra, Spain, Spain, 36071
      • Complexo Hospitalario Universitario de Pontevedra
    • Santander, Spain, Spain, 39008
      • Hospital Universitario Marqués de Valdecilla
    • Seville, Spain, Spain, 41013
      • Hospital Universitario Virgen del Rocio
• United Kingdom
  • GBR
    • London, GBR, United Kingdom, SE5 9RS
      • King's College Hospital NHS Foundation Trust
  • NGM
    • Nottingham, NGM, United Kingdom, NG7 2UH
      • The University of Nottingham - Nottingham Digestive Diseases Centre Biomedical Research Unit
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
    • Dothan, Alabama, United States, 36305
      • Digestive Health Specialists
  • Arizona
    • Chandler, Arizona, United States, 85224
      • The Institute for Liver Health
    • Glendale, Arizona, United States, 85306
      • Arizona Liver Health - Glendale
    • Tucson, Arizona, United States, 85712
      • Institute for Liver Health - Tucson
  • Arkansas
    • Little Rock, Arkansas, United States, 72205-6414
      • Liver Wellness Center - Little Rock
  • California
    • Canoga Park, California, United States, 91303
      • Hope Clinical Research, Inc.
    • Coronado, California, United States, 92118
      • Southern California GI & Liver Centers
    • La Jolla, California, United States, 92037
      • University of California San Diego Medical Center -La Jolla Multi-Specialty Clinics- Perlman Offices
    • Lancaster, California, United States, 93534
      • Om Research LLC
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Orange, California, United States, 92868
      • inSite Digestive Health Care - Orange
    • Pasadena, California, United States, 91105
      • California Liver Research Institute
    • Rialto, California, United States, 92377
      • Inland Empire Liver Foundation
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Anschutz Medical Campus
    • Colorado Springs, Colorado, United States, 80907-6262
      • Peak Gastroenterology Associates
  • Florida
    • Doral, Florida, United States, 33166
      • Integrity Clinical Research, LLC (ICR SITES) - Doral
    • Inverness, Florida, United States, 34452
      • Nature Coast Clinical Research, LLC
    • Jacksonville, Florida, United States, 32224-1865
      • Mayo Clinic Hospital - Florida
    • Lakewood Rch, Florida, United States, 34211
      • Florida Research Institute
    • Maitland, Florida, United States, 32751-3320
      • ClinCloud LLC
    • Miami, Florida, United States, 33147
      • Advanced Pharma Cr, Llc
    • Miami, Florida, United States, 33165
      • Genoma Research Group, Inc.
    • Ocoee, Florida, United States, 34761
      • Sensible Healthcare
    • Tampa, Florida, United States, 33614
      • Guardian Angel Health Services, Inc.
    • Zephyrhills, Florida, United States, 33542
      • Florida Medical Center & Research
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Digestive Healthcare of Georgia, P.C.
    • Macon, Georgia, United States, 31201
      • Gastroenterology Associates of Central Georgia, LLC
    • Marietta, Georgia, United States, 30060
      • Gastrointestinal Specialists of Georgia, PC
  • Illinois
    • Maywood, Illinois, United States, 60153
      • Loyola University Health System
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • IU Health University Hospital
    • South Bend, Indiana, United States, 46635
      • Michiana Gastroenterology, Inc.
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Kansas Medical Clinic PA
  • Kentucky
    • Louisville, Kentucky, United States, 40202-2046
      • University of Louisville Physicians - Cardiovascular Medicine Physicians Outpatient Center
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Tandem Clinical Research, LLC
    • New Orleans, Louisiana, United States, 70112-2600
      • Tulane Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • Mercy Medical Center - The Institute for Digestive Health and Liver Disease
  • Massachusetts
    • Boston, Massachusetts, United States, 02111-1552
      • Tufts Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System - Hemophilia and Thrombosis Treatment Center
    • Wyoming, Michigan, United States, 49519
      • Gastroenterology Associates of Western Michigan
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • Southern Therapy and Advanced Research (STAR) - Jackson
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • Kansas City Research Institute
  • Nevada
    • Las Vegas, Nevada, United States, 89109-6209
      • Excel Clinical Research - Las Vegas
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10003
      • Mount Sinai Beth Israel
    • New York, New York, United States, 10016-6402
      • NYU Langone Medical Center
    • New York, New York, United States, 10021
      • NewYork-Presbyterian Hospital/Weill Cornell Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 273302
      • UNC-Chapel Hill School of Medicine
    • Fayetteville, North Carolina, United States, 28304-3571
      • Cumberland Research Associates, LLC
    • Morehead City, North Carolina, United States, 28557
      • Lucas Research
  • Ohio
    • Cincinnati, Ohio, United States, 45249
      • Consultants for Clinical Research
    • Cincinnati, Ohio, United States, 45267-0595
      • University of Cincinnati Physicians Company, LLC
    • Cleveland, Ohio, United States, 44016
      • University Hospitals Cleveland Medical Center
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Milton S. Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19107
      • The Jefferson Digestive Health Institute - Thomas Jefferson University
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center (UPMC) - The Center for Liver Diseases
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina (MUSC)
  • Tennessee
    • Chattanooga, Tennessee, United States, 37411
      • University Diabetes & Endocrine Consultants
    • Chattanooga, Tennessee, United States, 37343-5470
      • Galen Medical Group - Ziegler Plaza
    • Germantown, Tennessee, United States, 38138
      • Gastro One - GI Diagnostic and Therapeutic Endoscopy Center - 1310 Wolf Park
    • Hermitage, Tennessee, United States, 37067
      • Associates in Gastroenterology
    • Johnson City, Tennessee, United States, 37604-6063
      • East Tennessee Research Institute - Gastrointestinal Associates of Northeast Tennessee, P.C.
  • Texas
    • Arlington, Texas, United States, 76012
      • Texas Clinical Research Institute, LLC
    • Austin, Texas, United States, 78757
      • Liver Specialists of Texas
    • Dallas, Texas, United States, 75203
      • Methodist Transplant Physicians
    • Denison, Texas, United States, 75020
      • Texoma Liver Center PLLC. - Denison
    • Edinburg, Texas, United States, 78539
      • South Texas Research Institute
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine - Baylor Clinic - Abdominal Transplant & Liver Disease Clinic
    • Houston, Texas, United States, 77099
      • Pioneer Research Solutions Inc - Houston - Stancliff Rd
    • San Antonio, Texas, United States, 78229
      • Pinnacle Clinical Research
    • San Antonio, Texas, United States, 78215
      • The Texas Liver Institute, Inc.
    • Waco, Texas, United States, 76710-2582
      • Impact Research Institute
  • Utah
    • Salt Lake City, Utah, United States, 84132-0001
      • University of Utah Health Care - UUHC - Kidney & Liver Clinic
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia School of Medicine
    • Fredericksburg, Virginia, United States, 22401-8425
      • Gastroenterology Associates of Fredericksburg
    • Newport News, Virginia, United States, 23602
      • Bon Secours Liver Institute of Virginia - Newport News
    • Richmond, Virginia, United States, 23226
      • Bon Secours Liver Institute of Virginia - Richmond
    • Richmond, Virginia, United States, 23249-0001
      • Hunter Holmes McGuire VA Medical Center
  • Washington
    • Spokane, Washington, United States, 99202-3462
      • Velocity Clinical Research, Spokane

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Each subject must meet all of the following criteria to be enrolled in this study:

1. Is male or female, ≥ 18 and ≤ 75 years of age at the time of Screening.
2. Is willing and able to provide written informed consent prior to the initiation of any study-specific procedures.

3. Has evidence of portal hypertension, with either one of the following:

   1. platelet count <150,000/mm3

      OR

   2. documented hepatic venous pressure gradient (HVPG) measurement >6 mmHg

      OR

   3. 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.

4. 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.
   • There is a historical liver biopsy showing steatosis but now with cirrhosis either by clinical examination, imaging, or biopsy. If there is a current biopsy, it does not show evidence of steatosis or steatohepatitis as histological lesions may have burned out. 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.
   • Patient with cirrhosis with current or previous imaging showing steatosis. There is no liver histology available. There is no evidence for a competing etiology. There are at least two co-existing or history of metabolic comorbidities with obesity or diabetes being one of them to corroborate a diagnosis of NAFLD.
   • For patients not meeting the above mentioned criteria, a screening liver biopsy is necessary.

   Note: All liver biopsy blocks and/or slides for eligibility assessments (including those from historical biopsies) will be reviewed by the central study pathologist while the subject is in Screening. Results from the central study pathologist must be available before the subject is randomized.

5. Absence of hepatocellular carcinoma (HCC) by valid imaging (eg, ultrasound, CT scan, or MRI) within 6 months prior to randomization. If no such imaging result is available, then ultrasound imaging should be performed as part of standard of care.
6. Patients with diabetes mellitus can be enrolled, if they are adequately controlled on a stable dose or doses of antidiabetic medication(s) for at least 3 months before Screening, and their screening HbA1c is ≤9.5%.
7. Patients on vitamin E or pioglitazone can be enrolled if they are on a stable dose and regimen for at least 3 months before screening, and the dose is expected to be held constant during the trial.
8. Patients on a statin can be enrolled if they are on a stable regimen for at least 3 months before Screening, and expected to be held stable during the trial.
9. Is not pregnant and must have a negative serum pregnancy test result prior to randomization.

10. Is of non-childbearing potential or if a fertile man or woman participating in heterosexual relations, agrees to use two acceptable means of contraception (ie, 2 effective methods of contraception, one of which must be a physical barrier method [eg, male or female condom, diaphragm] when combined with a highly effective method of contraception [ie, a method with a failure rate of <1% per year when used consistently and correctly]) throughout his/her participation in this study and for 90 days after discontinuation of study treatment.

    Highly effective forms of contraception include:

    • combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (such as oral, intravaginal, transdermal) methods
    • progestogen-only hormonal contraception associated with inhibition of ovulation (such as oral, injectable, implantable)
    • hormone-releasing intrauterine system (IUS)
    • intrauterine device (IUD)
    • bilateral tubal occlusion
    • a vasectomized partner, provided that partner is the sole sexual partner of the women of childbearing potential trial participant and that the vasectomized partner has received medical assessment of the surgical success
    • sexual abstinence (ie, a refraining from heterosexual intercourse during the entire period of the clinical trial, if it is the preferred and usual lifestyle of the subject).

    Surgically sterile males and females are not required to use contraception provided they have been considered surgically sterile for at least 6 months. Surgical sterility includes history of surgically successful vasectomy, hysterectomy, or bilateral salpingo-oophorectomy. Postmenopausal women who have been amenorrheic for at least 2 years at the time of Screening will be considered sterile.

11. If a lactating woman, agrees to discontinue nursing before the start of study treatment and refrain from nursing until 90 days after the last dose of study treatment.
12. If a man, agrees to refrain from sperm donation throughout the study period and for a period of 90 days following the last dose of investigational medicinal product (IMP). Female subjects may not begin a cycle of ova donation or harvest throughout the study period and for a period of 90 days following the last dose of IMP.

Exclusion Criteria:

Subjects meeting any of the following criteria will be excluded from the study:

1. 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.
2. 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.
3. 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).
4. Alcohol dependence (ie, a score >8 on the Alcohol Use Disorders Identification Test)
5. Narcotics or any other drug abuse or dependence in the last 5 years
6. Prior trans-jugular intrahepatic portal-systemic (TIPS) shunt procedure

7. 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
   • Wilson's disease
   • Hemochromatosis
   • Primary biliary cholangitis
   • Primary sclerosing cholangitis
   • Genetic hemochromatosis
   • History or planned liver transplantation
   • Alpha-1 antitrypsin deficiency
8. History of human immunodeficiency virus (HIV), or positive HIV test at Screening

9. Any of the following test or score:

   • serum alanine aminotransferase (ALT) > 5 × upper limit of normal (ULN)*

   • serum aspartate aminotransferase (AST) > 5 × ULN*

     *Screening values will be obtained at Screening Visit 1 (SV1) and Screening Visit 2(SV2) (which will be separated by 2 to 4 weeks). A second screening value that is >50% higher than the first value should prompt re-evaluation of the severity of the underlying liver disease and eligibility for this trial. If a transaminase level at SV2 is >33% different from the level at SV1, then additional measurements should be performed at Screening Visit 3 (SV3). In such cases, the baseline transaminase levels will be established for subjects using the mean value of 4 evaluations [ie, at SV1, SV2, SV3, and Baseline (ie, pre-dose during Visit 1)].

   • serum alkaline phosphatase (ALP) > 2 × ULN
   • mean platelet count < 50,000/mm3
   • total bilirubin ≥ 2.0 mg/dL (subjects with a documented history of Gilbert's syndrome can be enrolled if the direct bilirubin is within normal reference range)
   • model for end-stage liver disease (MELD) score ≥12
   • Child-Turcotte-Pugh (CTP) Score ≥7 Note: Following Phase 2b, subjects with CTP scores ≥7 may be enrolled if recommended* by the Data Safety Monitoring Board (DSMB) and approved by the Trial Steering Committee (TSC), based on the planned interim analysis (IA). [*based on DSMB review of preliminary results from a separate hepatic impairment clinical trial (Study GT-032) which is assessing belapectin safety and pharmacokinetic (PK) in cirrhotic subjects with CTP scores ≥7.
   • estimated glomerular filtration rate < 45 mL/min* *Note: per Modification of Diet in Renal Disease algorithm
10. Taking an angiotensin converting enzyme inhibitor, angiotensin II receptor blocker, or β-1 selective adrenergic receptor inhibitor, unless on a stable regimen for at least 3 months prior to Screening and no changes in the regimen are anticipated during the study. Subjects taking a non-selective beta blocker are not eligible to be enrolled (Investigators are encouraged to substitute another medication, if clinically warranted).
11. History of major surgery during Screening.
12. History of a solid organ transplant requiring immunosuppressive therapy.
13. History of bariatric surgery within 1 year of randomization, or plan to undergo bariatric surgery during the study.
14. Has positive screening test for illicit drugs of abuse at Screening.
15. Has participated in an investigational new drug study within 30 days or 5 half-lives whichever is longer, prior to randomization.
16. Has a history of malignancy within 5 years of randomization, except for basal cell carcinoma, squamous cell carcinoma, and adequately treated in situ uterine cervical cancer.
17. Has clinically significant cardiovascular disease (eg, uncontrolled hypertension, myocardial infarction, unstable angina), New York Heart Association Grade II or greater congestive heart failure, serious cardiac arrhythmia requiring intervention (eg, pacemaker/ablation) or Grade II or greater peripheral vascular disease.
18. Has a history of clinically significant hematologic, renal, hepatic, pulmonary, neurological, psychiatric, gastrointestinal, systemic inflammatory, metabolic or endocrine disorder or any other condition that, in the opinion of the Investigator, renders the subject a poor candidate for inclusion into the study.
19. Has known allergies to the IMP or any of its excipients.
20. Has previously received belapectin within 6 months of randomization.
21. Is an employee or family member of the Investigator or study center personnel.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: belapectin 2 mg/kg lean body mass (LBM); 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; intravenous; Other Names: GR-MD-02; galactoarabino rhamnogalacturonate
Experimental: belapectin 4 mg/kg lean body mass (LBM); 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; intravenous; Other Names: GR-MD-02; galactoarabino rhamnogalacturonate
Placebo Comparator: Placebo; 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; intravenous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy: Cumulative Incidence Rate of Patients in the Belapectin Treatment Groups, Compared to Placebo, Who Develop Varices (Esophageal or Gastric) Requiring Treatment	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	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	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	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)	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
Efficacy: Cumulative Incidence Rate of Patients in the Belapectin Treatment Groups, Compared to Placebo, Who Develop Mortality (All-cause)	Efficacy: Cumulative incidence rate of patients in the belapectin treatment groups, compared to placebo, who develop mortality (all-cause).	Through study end, 78 weeks or 156 weeks
Efficacy: Cumulative Incidence Rate of Patients in the Belapectin Treatment Groups, Compared to Placebo, Who Develop Liver Transplant	Efficacy: Cumulative incidence rate of patients in the belapectin treatment groups, compared to placebo, who develop liver transplant.	Through study end, 78 weeks or 156 weeks
Efficacy: Cumulative Incidence Rate of Patients in the Belapectin Treatment Groups, Compared to Placebo, Who Develop Model for End-stage Liver Disease (MELD) Score ≥15	Efficacy: Cumulative incidence rate of patients in the belapectin treatment groups, compared to placebo, who develop model for end-stage liver disease (MELD) score ≥15.	Through study end, 78 weeks or 156 weeks
Efficacy: Cumulative Incidence Rate of Patients in the Belapectin Phase 3 Treatment Group Who Progress to Large Varices (Gastric or Esophageal) or Develop Red Wales Compared to Placebo.	Efficacy: Cumulative incidence rate of patients in the belapectin Phase 3 treatment group who progress to large varices (gastric or esophageal) or develop red wales compared to placebo.	Through study end, 78 weeks or 156 weeks
Efficacy: Event-free Survival by Time to First Cirrhosis Related Clinical Event, Progression to Large Varices or Red Wales	Number of participants who experienced first cirrhosis related clinical event, progression to large varices or red wales by week 78.	Through study end, 78 weeks or 156 weeks
Efficacy: Event-free Survival by Time to First Cirrhosis Related Clinical Event, Esophageal Variceal Hemorrhage Requiring Hospitalization	Number of participants who experienced first cirrhosis related clinical event, esophageal variceal hemorrhage requiring hospitalization by week 78.	Through study end, 78 weeks or 156 weeks
Efficacy: Event-free Survival by Time to First Cirrhosis Related Clinical Event, Clinically Significant Ascites Requiring Hospitalization	Number of participants who experienced first cirrhosis related clinical event, clinically significant ascites requiring hospitalization by week 78.	Through study end, 78 weeks or 156 weeks
Efficacy: Event-free Survival by Time to First Cirrhosis Related Clinical Event, Spontaneous Bacterial Peritonitis	Number of participants who experienced first cirrhosis related clinical event, spontaneous bacterial peritonitis by week 78.	Through study end, 78 weeks or 156 weeks
Efficacy: Event-free Survival by Time to First Cirrhosis Related Clinical Event, Overt Hepatic Encephalopathy (West Haven Score ≥2 and Requiring Hospitalization)	Number of participants who experienced first cirrhosis related clinical event, overt hepatic encephalopathy (West Haven score ≥2 and requiring hospitalization) by week 78.	Through study end, 78 weeks or 156 weeks
Efficacy: Event-free Survival by Time to First Cirrhosis Related Clinical Event, Child-Turcotte-Pugh (CTP) Score Increase of ≥2 Points (From Baseline)	Number of participants who experienced first cirrhosis related clinical event, Child-Turcotte-Pugh (CTP) score increase of ≥2 points (from baseline) by week 78.	Through study end, 78 weeks or 156 weeks
Efficacy: Event-free Survival by Time to First Cirrhosis Related Clinical Event, Model for End-stage Liver Disease (MELD) Score Increase to ≥15 as Measured on 2 Consecutive Occasions	Number of participants who experienced first cirrhosis related clinical event, model for end-stage liver disease (MELD) score increase to ≥15 as measured on 2 consecutive occasions by week 78.	Through study end, 78 weeks or 156 weeks
Efficacy: Event-free Survival by Time to First Cirrhosis Related Clinical Event, Liver Transplant	Number of participants who experienced first cirrhosis related clinical event, liver transplant by week 78.	Through study end, 78 weeks or 156 weeks
Efficacy: Event-free Survival by Time to First Cirrhosis Related Clinical Event, Liver-related Death	Number of participants who experienced first cirrhosis related clinical event, liver-related death by week 78.	Through study end, 78 weeks or 156 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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
Safety: Incidence of Adverse Events	Safety: Incidence of adverse events.	Through study end, 78 weeks or 156 weeks

Collaborators and Investigators

• Sponsor: Galectin Therapeutics Inc.
• Investigators: Study Director: Khurram Jamil, M.D., Galectin Therapeutics Inc.

Publications and helpful links

Helpful Links

• Hepatology Journal Article- Efficacy and safety of belapectin for the prevention of esophageal varices in patients with MASH cirrhosis: The randomized, placebo-controlled NAVIGATE trial

Study record dates

Study Major Dates

• Study Start (Actual): June 25, 2020
• Primary Completion (Actual): March 11, 2025
• Study Completion (Actual): April 10, 2025

Study Registration Dates

• First Submitted: April 24, 2020
• First Submitted That Met QC Criteria: April 24, 2020
• First Posted (Actual): April 28, 2020

Study Record Updates

• Last Update Posted (Actual): June 30, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: NASH; portal hypertension; cirrhosis; esophageal varices; GR-MD-02; belapectin; nonalcoholic steatohepatitis (NASH) cirrhosis
• Additional Relevant MeSH Terms: Pathologic Processes; Digestive System Diseases; Gastrointestinal Diseases; Liver Diseases; Esophageal Diseases; Fatty Liver; Pathological Conditions, Signs and Symptoms; Fibrosis; Non-alcoholic Fatty Liver Disease; Hypertension, Portal; Esophageal and Gastric Varices; belapectin
• Other Study ID Numbers: GT-031

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No