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

Cirrhosis Clinical Trial

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Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04365868
• Other study ID #: GT-031
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: June 22, 2020
• Est. completion date: December 2024

Study information

• Verified date: November 2023
• Source: Galectin Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 357
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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 ß-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.

Related Conditions & MeSH terms

• Cirrhosis
• Esophageal and Gastric Varices
• Fatty Liver
• Fibrosis
• Liver Cirrhosis
• NASH - Nonalcoholic Steatohepatitis
• Non-alcoholic Fatty Liver Disease
• Prevention of Esophageal Varices
• Varicose Veins

Intervention

Drug:
• belapectin
intravenous
• Placebo
intravenous

Locations

Country	Name	City	State
Argentina	Hospital Británico de Buenos Aires	Buenos Aires	ARG
Argentina	Centro de Investigaciones Metabólicas (CINME)	Capital federal	ARG
Argentina	Hospital Italiano de Buenos Aires	Ciudad Autonoma de Buenos aires	ARG
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Box Hill Hospital	Box Hill	Victoria
Australia	Monash Medical Centre Clayton	Clayton	Victoria
Australia	Nepean Hospital	Kingswood	New South Wales
Australia	Fiona Stanley Hospital	Murdoch	Western Australia
Belgium	Clinique Universitaire De Bruxelles Hôpital Erasme VZW	Brussels	BEL
Belgium	Antwerp University Hospital	Edegem	Antwerpen
Belgium	AZ Maria Middelares	Gent	VOV
Belgium	Universitair Ziekenhuis Gent	Gent	VOV
Belgium	Groupe sante CHC - Clinique du MontLegia	Liège	WLG
Canada	Brampton Civic Hospital	Brampton	Ontario
Canada	University of Calgary - Heritage Medical Research Clinic - Foothills Hospital Center	Calgary	Alberta
Canada	Centre Hospitalier de l'Université de Montréal (CHUM)	Montréal	Quebec
Canada	Toronto Liver Centre	Toronto	Ontario
Canada	Pacific Gastroenterology Associates	Vancouver	British Columbia
Chile	Hospital de La Serena	La Serena	CHL
Chile	Clínica Universidad de los Andes	Santiago	CHL
Chile	Hospital Clínico Universidad de Chile	Santiago
Chile	Centro de Investigaciones Clinicas Vina del Mar	Viña Del Mar	CHL
France	Centre Hospitalier Universitaire d'Amiens	Amiens
France	Hôpital Avicenne	Bobigny
France	CHU Hôpital Henri Mondor	Créteil
France	CHU de Grenoble	Grenoble
France	Hôpital de la Croix-Rousse	Lyon
France	CHRU Montpellier - Saint Eloi	Montpellier
France	CHU Nancy - Hôpital Brabois	Nancy
France	CHU de Nice - L'Archet	Nice
France	Hôpital Cochin	Paris
France	Hôpitaux Universitaires de Strasbourg - Hôpital Civil	Strasbourg
Germany	Goethe-Universität Frankfurt am Main	Frankfurt am Main
Germany	EUGASTRO GmbH	Leipzig	SN
Germany	Universitatsmedizin der Johannes Gutenberg-Universitat Mainz	Mainz	RP
Israel	Soroka Medical Center	Be'er Sheva
Israel	Carmel Medical Center	Haifa
Israel	Rambam Medical Center	Haifa
Israel	Hadassah Ein Karem Hospital	Jerusalem
Israel	Holy Family Hospital	Nazareth
Israel	Rabin Medical Center - Beilinson Hospital	Petah Tiqwa
Israel	The Chaim Sheba Medical Center - The Center for Liver Diseases	Ramat Gan
Israel	Tel Aviv Sourasky Medical Center	Tel-Aviv
Korea, Republic of	Digestive Research Alliance of Michiana, LLC	Incheon
Korea, Republic of	Hanyang University Seoul Hospital	Seoul	KOR
Korea, Republic of	Yonsei University, Wonju Severance Christian Hospital	Seoul	KOR
Korea, Republic of	Yonsei University, Wonju Severance Christian Hospital	Wonju	KOR
Mexico	CICPA Centro de Investigación Clinica del Pacifico	Acapulco de Juárez	Guerrero
Mexico	Centro de Investigación Medica de Aguascalientes	Aguascalientes
Mexico	Investigacion Biomedica para el desarrollo de farmacos SA de CV	Benito Juarez	Ciudad De México
Mexico	MEDIVEST Centro de Investigacion integral	Chihuahua
Mexico	Consultorio Medico	Ciudad De Mexico	MEX
Mexico	CEMDEC SA de CV Centro Mexicano de Desarrollo de Estudios Clinicos	Cuauhtémoc	Ciudad De Mexico
Mexico	Centro de Investigacion Medico Biologica y Terapia Avanzada SC	Guadalajara	Jalisco
Mexico	Medical Care and Research SA de CV	Mérida	Yucatan
Mexico	Centro Especializado en Diabetes, Obesidad y Pevencion de enfermedades Cadiovasculares SC.	Miguel Hidalgo	Ciudad De México
Mexico	Hospital Universitario Dr. Jose Eleuterio Gonzalez Servicio de Gastroenterología	Monterrey	Nuevo Leon
Mexico	Centro de Investigacion Clinica de Oaxaca	Oaxaca
Mexico	Oaxaca Site Management Organization SC.	Oaxaca de Juarez	Oaxaca
Mexico	Investigacion Biomedica para el desarrollo de farmacos SA de CV	Zapopan	Jalisco
Poland	SP CSK im Prof. Kornela Gibinskiego Slaskiego Uniwersytetu Medycznego w Katowicach	Katowice	SL
Poland	Medical University of Lodz	Lódz	LD
Poland	ID Clinic	Myslowice	SL
Poland	Medyczny Katedra i Klinika Chorób Zakaznych, Chorób Watroby i Nabytych Niedoborów Odpornosciowych	Wroclaw
Puerto Rico	Fundacion de Investigacion de Diego	San Juan
Spain	Hospital del Mar Research Institute	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid	ESP
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Hospital Universitario Puerta de Hierro - Majadahonda	Majadahonda
Spain	Complexo Hospitalario Universitario de Pontevedra	Pontevedra
Spain	Hospital Universitario Marqués de Valdecilla	Santander
Spain	Hospital Universitario Virgen del Rocío	Sevilla
United Kingdom	King's College Hospital NHS Foundation Trust	London	GBR
United Kingdom	The University of Nottingham - Nottingham Digestive Diseases Centre Biomedical Research Unit	Nottingham	NGM
United States	University of Michigan	Ann Arbor	Michigan
United States	Texas Clinical Research Institute, LLC	Arlington	Texas
United States	Digestive Healthcare of Georgia, P.C.	Atlanta	Georgia
United States	University of Colorado Anschutz Medical Campus	Aurora	Colorado
United States	Liver Specialists of Texas	Austin	Texas
United States	Mercy Medical Center - The Institute for Digestive Health and Liver Disease	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Tufts Medical Center	Boston	Massachusetts
United States	Hope Clinical Research, Inc.	Canoga Park	California
United States	The Institute for Liver Health	Chandler	Arizona
United States	UNC-Chapel Hill School of Medicine	Chapel Hill	North Carolina
United States	Medical University of South Carolina (MUSC)	Charleston	South Carolina
United States	University of Virginia School of Medicine	Charlottesville	Virginia
United States	Galen Medical Group - Ziegler Plaza	Chattanooga	Tennessee
United States	University Diabetes & Endocrine Consultants	Chattanooga	Tennessee
United States	Consultants for Clinical Research	Cincinnati	Ohio
United States	University of Cincinnati Physicians Company, LLC	Cincinnati	Ohio
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Peak Gastroenterology Associates	Colorado Springs	Colorado
United States	The Ohio State University Wexner Medical Center	Columbus	Ohio
United States	Southern California GI & Liver Centers	Coronado	California
United States	Methodist Transplant Physicians	Dallas	Texas
United States	Texoma Liver Center PLLC. - Denison	Denison	Texas
United States	Henry Ford Health System - Hemophilia and Thrombosis Treatment Center	Detroit	Michigan
United States	Integrity Clinical Research, LLC (ICR SITES) - Doral	Doral	Florida
United States	Digestive Health Specialists	Dothan	Alabama
United States	South Texas Research Institute	Edinburg	Texas
United States	Cumberland Research Associates, LLC	Fayetteville	North Carolina
United States	Gastroenterology Associates of Fredericksburg	Fredericksburg	Virginia
United States	Gastro One - GI Diagnostic and Therapeutic Endoscopy Center - 1310 Wolf Park	Germantown	Tennessee
United States	Arizona Liver Health - Glendale	Glendale	Arizona
United States	Associates in Gastroenterology	Hermitage	Tennessee
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Baylor College of Medicine - Baylor Clinic - Abdominal Transplant & Liver Disease Clinic	Houston	Texas
United States	Pioneer Research Solutions Inc - Houston - Stancliff Rd	Houston	Texas
United States	IU Health University Hospital	Indianapolis	Indiana
United States	Nature Coast Clinical Research, LLC	Inverness	Florida
United States	Southern Therapy and Advanced Research (STAR) - Jackson	Jackson	Mississippi
United States	Mayo Clinic Hospital - Florida	Jacksonville	Florida
United States	East Tennessee Research Institute - Gastrointestinal Associates of Northeast Tennessee, P.C.	Johnson City	Tennessee
United States	Kansas City Research Institute	Kansas City	Missouri
United States	University of California San Diego Medical Center -La Jolla Multi-Specialty Clinics- Perlman Offices	La Jolla	California
United States	Florida Research Institute	Lakewood Ranch	Florida
United States	Om Research LLC	Lancaster	California
United States	Excel Clinical Research - Las Vegas	Las Vegas	Nevada
United States	Liver Wellness Center - Little Rock	Little Rock	Arkansas
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	University of Louisville Physicians - Cardiovascular Medicine Physicians Outpatient Center	Louisville	Kentucky
United States	Gastroenterology Associates of Central Georgia, LLC	Macon	Georgia
United States	ClinCloud LLC	Maitland	Florida
United States	Gastrointestinal Specialists of Georgia, PC	Marietta	Georgia
United States	Tandem Clinical Research, LLC	Marrero	Louisiana
United States	Loyola University Health System	Maywood	Illinois
United States	Advanced Pharma CR, LLC	Miami	Florida
United States	Genoma Research Group, Inc.	Miami	Florida
United States	Lucas Research	Morehead City	North Carolina
United States	Tulane Cancer Center	New Orleans	Louisiana
United States	Columbia University Medical Center	New York	New York
United States	Mount Sinai Beth Israel	New York	New York
United States	NewYork-Presbyterian Hospital/Weill Cornell Medical Center	New York	New York
United States	NYU Langone Medical Center	New York	New York
United States	Bon Secours Liver Institute of Virginia - Newport News	Newport News	Virginia
United States	Sensible Healthcare	Ocoee	Florida
United States	inSite Digestive Health Care - Orange	Orange	California
United States	California Liver Research Institute	Pasadena	California
United States	The Jefferson Digestive Health Institute - Thomas Jefferson University	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center (UPMC) - The Center for Liver Diseases	Pittsburgh	Pennsylvania
United States	Inland Empire Liver Foundation	Rialto	California
United States	Bon Secours Liver Institute of Virginia - Richmond	Richmond	Virginia
United States	Hunter Holmes McGuire VA Medical Center	Richmond	Virginia
United States	University of Utah Health Care - UUHC - Kidney & Liver Clinic	Salt Lake City	Utah
United States	Pinnacle Clinical Research	San Antonio	Texas
United States	The Texas Liver Institute, Inc.	San Antonio	Texas
United States	Michiana Gastroenterology, Inc.	South Bend	Indiana
United States	Velocity Clinical Research, Spokane	Spokane	Washington
United States	Guardian Angel Health Services, Inc.	Tampa	Florida
United States	Kansas Medical Clinic PA	Topeka	Kansas
United States	Institute for Liver Health - Tucson	Tucson	Arizona
United States	Impact Research Institute	Waco	Texas
United States	Gastroenterology Associates of Western Michigan	Wyoming	Michigan
United States	Florida Medical Center & Research	Zephyrhills	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Galectin Therapeutics Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Canada,  Chile,  France,  Germany,  Israel,  Korea, Republic of,  Mexico,  Poland,  Puerto Rico,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	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
Other	Exploratory Efficacy: Difference in Chronic Liver Disease Questionnaire (CLDQ) scores between belapectin and placebo treatment during Phase 2b and Phase 3	The difference in Chronic Liver Disease Questionnaire scores between belapectin and placebo treatment during Phase 2b and Phase 3 will be observed; Subject responses to the questionnaire are based on a scale from 1 to 7, with 1 being maximum frequency and 7 being none at all. Scores indicative of higher frequency, indicate worse outcomes.	Through study end, 78 weeks or 156 weeks
Other	Safety: Incidence of adverse events	Incidence of adverse events	Through study end, 78 weeks or 156 weeks
Primary	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	Efficacy: Cumulative incidence rate of patients in the belapectin treatment groups, compared to placebo, who develop varices (esophageal or gastric) requiring treatment	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
Secondary	Efficacy: Cumulative incidence rate of patients in the belapectin treatment groups, compared to placebo, who develop variceal bleed requiring hospitalization	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
Secondary	Efficacy: Cumulative incidence rate of patients in the belapectin treatment groups, compared to placebo, who develop clinically significant ascites requiring hospitalization	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
Secondary	Efficacy: Cumulative incidence rate of patients in the belapectin treatment groups, compared to placebo, who develop spontaneous bacterial peritonitis	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
Secondary	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)	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
Secondary	Efficacy: Cumulative incidence rate of patients in the belapectin treatment groups, compared to placebo, who develop mortality (all-cause)	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
Secondary	Efficacy: Cumulative incidence rate of patients in the belapectin treatment groups, compared to placebo, who develop liver transplant	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
Secondary	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	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
Secondary	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.	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
Secondary	Efficacy: Event-free survival by time to first cirrhosis related clinical event, progression to large varices or red wales	Event-free survival by time to first cirrhosis related clinical event, progression to large varices or red wales	Through study end, 78 weeks or 156 weeks
Secondary	Efficacy: Event-free survival by time to first cirrhosis related clinical event, esophageal variceal hemorrhage requiring hospitalization	Event-free survival by time to first cirrhosis related clinical event, esophageal variceal hemorrhage requiring hospitalization	Through study end, 78 weeks or 156 weeks
Secondary	Efficacy: Event-free survival by time to first cirrhosis related clinical event, clinically significant ascites requiring hospitalization	Event-free survival by time to first cirrhosis related clinical event, clinically significant ascites requiring hospitalization	Through study end, 78 weeks or 156 weeks
Secondary	Efficacy: Event-free survival by time to first cirrhosis related clinical event, spontaneous bacterial peritonitis	Event-free survival by time to first cirrhosis related clinical event, spontaneous bacterial peritonitis	Through study end, 78 weeks or 156 weeks
Secondary	Efficacy: Event-free survival by time to first cirrhosis related clinical event, overt hepatic encephalopathy (West Haven score =2 and requiring hospitalization)	Event-free survival by time to first cirrhosis related clinical event, overt hepatic encephalopathy (West Haven score =2 and requiring hospitalization)	Through study end, 78 weeks or 156 weeks
Secondary	Efficacy: Event-free survival by time to first cirrhosis related clinical event, Child-Turcotte-Pugh (CTP) score increase of =2 points (from baseline)	Event-free survival by time to first cirrhosis related clinical event, Child-Turcotte-Pugh (CTP) score increase of =2 points (from baseline)	Through study end, 78 weeks or 156 weeks
Secondary	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	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	Through study end, 78 weeks or 156 weeks
Secondary	Efficacy: Event-free survival by time to first cirrhosis related clinical event, liver transplant	Event-free survival by time to first cirrhosis related clinical event, liver transplant	Through study end, 78 weeks or 156 weeks
Secondary	Efficacy: Event-free survival by time to first cirrhosis related clinical event, liver-related death	Event-free survival by time to first cirrhosis related clinical event, liver-related death	Through study end, 78 weeks or 156 weeks