Clinical Trial to Evaluation the Safety and Efficacy of GR-MD-02 for the Treatment of Liver Fibrosis and Resultant Portal Hypertension in Patients With Nash Cirrhosis

Inclusion Criteria

• Has a HVPG measurement ≥6 mm Hg.
• Has a liver biopsy with cirrhosis (Ishak stage 5 or 6) presumably due to NASH. A liver biopsy diagnosis of cirrhosis presumably due to NASH will include the following 3 categories:
• Cirrhosis with a definitive pathological diagnosis of NASH (presence of fat, ballooning degeneration, and inflammation);
• Cirrhosis wherein the biopsy contains either fat (>5%) or ballooning hepatocytes with no evidence of viral hepatitis or other liver disease; or
• Cirrhosis with no evidence of viral hepatitis or other liver disease in a subject with at least a 5 year history of obesity (BMI ≥30) or at least a 5 year history of diabetes mellitus (as defined by diagnosis by a physician and treatment with at least 1 antidiabetic medication).
• Is ≥18 years of age and ≤75 years of age at the time of screening.
• Absence of hepatocellular carcinoma by valid imaging (liver ultrasound, triple phase computed tomography of liver or magnetic resonance imaging of liver) within 6 months prior to randomization. If there is not such test available, then it should be performed as part of standard of care.
• Is willing and able to provide written informed consent prior to the initiation of any study specific procedures.
• Is not pregnant and must have a negative serum pregnancy test result prior to randomization.
• If a fertile man or woman participating in heterosexual relations, agrees to use effective means of contraception (ie, 2 effective methods of contraception, one of which must be a physical barrier method).
• Effective forms of contraception include condom, hormonal methods (birth control pills, injections or implants), diaphragm, cervical cap, or intrauterine device throughout his/her participation in this study and for 90 days after discontinuation of study treatment. 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 vasectomy, hysterectomy, bilateral salpingo oophorectomy, or bilateral tubal ligation. Postmenopausal women who have been amenorrheic for at least 2 years at the time of screening will be considered sterile.
• 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.
• 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 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.
• Prior to randomization, any subject on statins, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, or β 1 selective adrenergic receptor inhibitors should have been on a stable dose for at least 2 months and all attempts should be made to continue the subject on the same dose of the medication for the duration of study participation.

Exclusion Criteria

• Has a history of hepatic decompensation including any episode of variceal bleeding, ascites not controlled by medication, or overt hepatic encephalopathy (defined by the clinical judgment of the principal investigator but shall include the presence of lethargy, disorientation, inappropriate behavior, and the presence of asterixis).
• Has a presence of medium or large varices or varices with red signs regardless of size based on endoscopy.
• Small varices are defined by veins that occupy 50%).
• Red signs include red wale markings (dilated venules oriented longitudinally on the variceal surface), cherry red spots (small, red, spotty dilated venules usually approximately 2 mm in diameter on the variceal surface) or hematocystic spots (large, round, crimson red projection >3 mm that look like a blood blister on the variceal surface).
• Has had a prior transjugular porto systemic shunt procedu