Esophageal Varices in NASH Cirrhosis MedDRA version: 20.0 Level: LLT Classification code 10009214 Term: Cirrhosis of liver without mention of alcohol System Organ Class: 100000004871 MedDRA version: 21.1 Level: LLT Classification code 10055489 Term: Esophageal varices in cirrhosis of liver System Organ Class: 100000004856
Conditions
Sponsors
Galectin Therapeutics Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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. Has evidence of portal hypertension, with 3. either one of the following: a. platelet count 6 mmHg OR c. 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 kPa - AST/ALT >1. 4. Has a history confirming 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 or history of 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 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 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 physical 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. 5. Absence of HCC by valid imaging (e.g. ultrasound, CT scan or MRI) within 6 months prior to randomization. If no such imaging result is available, then it 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
Exclusion criteria
Exclusion criteria: 1. Presence of esophageal, gastroesophageal, or isolated gastric varices, based on an upper GI 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, as per medical history. 4. 4. Alcohol dependence. 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 ALT > 5 × upper limit of normal (ULN) • serum AST > 5 × ULN • serum ALP > 2 × ULN • mean platelet count 12 • CTP Score =7 • estimated creatinine clearance < 45 mL/min 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 the 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, pulmo
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of 2 mg/kg and 4 mg/kg lean body mass (LBM) of belapectin (GR MD 02) compared to placebo in preventing the development of esophageal varices.;Secondary Objective: To evaluate the effect of belapectin on composite clinical outcomes.;Primary end point(s): Proportion of patients in the belapectin treatment groups who develop esophageal varices at 78 weeks (18 months) of treatment compared to placebo;Timepoint(s) of evaluation of this end point: Phase 2b-Phase 3 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary Efficacy Endpoint Incidence rate of patients in the belapectin treatment groups, compared to placebo, who develop any of the following: 1) varices (esophageal or gastric) requiring treatment, 2) variceal bleed requiring hospitalization, 3) clinically significant ascites requiring hospitalization, 4) spontaneous bacterial peritonitis, 5) overt hepatic encephalopathy (West Haven score =2 and requiring hospitalization), 6) mortality (all-cause), 7) liver transplant, 8) model for end-stage liver disease (MELD) score =15;Timepoint(s) of evaluation of this end point: Phase 2b-Phase 3 | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Chile, France, Germany, Israel, Korea, Republic of, Mexico, Poland, Spain, United Kingdom, United States
Contacts
Public ContactSteve Schoenfeld
Galectin Therapeutics Inc.
Outcome results
None listed