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. 3. Has evidence of portal hypertension, with at least 2 of the following: a. platelet count 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. • For patients without a historical liver biopsy with slides available for review by the central study pathologist, a screening liver biopsy is required. 5. Absence of HCC by valid imaging (liver ultrasound, triple phase CT or MRI of liver) 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 type 2 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 study enrollment, 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 dose and regimen for at least 3 months before screening, and the dose is expected to be held constant during the trial. 9. Is not pregnant and must have a negative serum p
Exclusion criteria
Exclusion criteria: 1. Presence of esophageal, gastroesophageal, or isolated gastric varices, based on an upper GI EGD exam conducted within 2 months of randomization. Patients with clearly defined gastric fundal varices should be excluded, but patients with gastropathy could be considered for enrollment after approval/discussion with the Medical Monitor. 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 after Screening but before randomization. 3. Known or suspected abuse of alcohol, as per medical history. 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 chronic liver disease other than NASH, including but not restricted to: • Viral hepatitis, unless eradicated at least 3 years prior to Screening • positive for hepatitis A • positive hepatitis B surface antigen • positive hepatitis C virus (HCV) ribonucleic acid (tested for in case of positive HCV antibody, at the latest 2 weeks prior to randomization) • Suspicion of drug-induced liver disease • Alcoholic liver disease • Autoimmune hepatitis • Wilson’s disease • Hemochromatosis • Primary biliary cholangitis (also termed primary biliary cirrhosis) • Primary sclerosing cholangitis • Genetic hemochromatosis • Known or suspected HCC • History or planned liver transplantation, or current MELD score =12 • Alpha-1 antitrypsin deficiency 8. Type 1 diabetes or poorly controlled Type 2 diabetes mellitus (HbA1c >9.5%) 9. History of human immunodeficiency virus (HIV), or positive HIV test at Screening 10. Any of the following test or score values during Screening Visit (SV) 1, SV2, and SV3 (if required/available): • serum ALT > 5 × upper limit of normal (ULN) • serum AST > 5 × ULN • serum ALP > 1.5 × ULN • platelet count < 150,000/mm3 • albumin = 3.5 g/dL • INR =1.5 (without anticoagulant therapy) • 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) • MELD score =12 • CTP Score =7 • estimated creatinine clearance < 45 mL/min 11. Taking a statin, angiotensin converting enzyme inhibitor, angiotensin II receptor blocker, or ß-1 selective adrenergic receptor inhibitor, unless on a stable dose and dosing regimen for at least 3 months prior to screening, and no changes in the dose or dosing regimen are anticipated during the entire study. Subjects taking a non-selective beta blocker are not eligible to be enrolled. 12. History of major surgery within 8 weeks of randomization, significant traumatic injury within 6 months, or anticipation of need for major surgical procedure during the course of the study. 13. History of a solid organ transplant requiring continuing immunosuppressive therapy. 14. History of bariatric surgery within 3 years of randomization, or plan to undergo weight reduction surgery or participate in weight reduction programs during the study. 15. Has positive screening test for illicit drugs of abuse, including, but not limited to, amphetamines, cocaine, or non-prescription opiates (eg, heroin, morphine) at Screening. 16. Has participated in an investigational new drug study within 30 days or 5 ha
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
Australia, Belgium, Canada, France, Germany, Israel, Korea, Republic of, Mexico, Poland, Spain, United Kingdom, United States
Contacts
Public ContactJ.Rex Horton
Galectin Therapeutics Inc.
Outcome results
None listed