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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

Primary Objective

Primary 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

Study category: Digestive Health

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Description

This study will be conducted in 2 sequential stages. You are being invited to participate in both stages of this study. The entire study period will be of approximately 39 months. Stage 1 (Phase 2b) will include approximately 315 patients and will consist of a screening period (about 2 months) and a study treatment period during which treatment will be administered by intravenous infusion every other week for a period of approximately 18 months (about 40 infusions). Stage 2 (Phase 3) will include the patients that completed Stage 1 and additional 210 new patients. Similar to Stage 1, Stage 2 will consist of a study treatment administered by intravenous infusion every other week for a period of approximately 18 months (about 40 infusions). The complete study treatment period will consist of approximately 36 months (about 80 infusions).

Details
Age

Adult

Eligibility

Key eligibility criteria 1. NASH cirrhosis 2. Without varices 3. CTP score <7 4. Clinical signals suggesting portal hypertension, with at least 2 of: &#8226; thrombocytopenia &#8226; spleen size &#8805; 15 cm &#8226; evidence of collaterals by imaging

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 <150,000/mm3 b. spleen size ≥ 15 cm (by documented MRI, CT scan, or ultrasound imaging) c. collateral vessels (by documented MRI or ultrasound imaging or physical examination, ie, caput medusae) 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.  For patients without a historical liver biopsy with slides available for review by the central study pathologist, a screening liver biopsy is required. 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, and must meet definitions for diagnosis of either Definitive cirrhosis (1a, 1b, and 1c) or Probable cirrhosis (2a, per Liver Forum criteria (Appendix 2). Results from the central study pathologist must be available before the subject is randomized. 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 screeni

Type of Study

Treatment

Scope

National

Locations

Outpatient CTRC
University of Colorado Hospital

Principal Investigator
Amanda Wieland,  MD

Amanda Wieland, MD

Study ID

Protocol Number: 20-2433

More information available at ClinicalTrials.gov: NCT04365868

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