Clinical Trial: 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

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Multicenter, Randomized, Placebo-controlled, Double-blind, Parallel-group, Phase 2 Clinical Trial to Evaluation the Safety and Efficacy of GR-MD-02 for the Treatment of Liver Fibrosis and Resultant

Brief Summary:

Study GT 026 is a Phase 2, multicenter, parallel group, North American, randomized, placebo controlled, double blind study. This study will enroll subjects with portal hypertension (HVPG greater than or equal to 6 mm Hg) who also have a liver biopsy with cirrhosis (Ishak stage 5 or 6), presumably due to NASH, excluding subjects with medium and large varices and those with decompensated cirrhosis.

Subjects with portal hypertension and cirrhosis will be randomly assigned (1:1:1 ratio) to receive 1 of 3 treatment assignments including placebo, GR MD 02 in a dose of 2 mg/kg lean body mass, or GR MD 02 in a dose of 8 mg/kg lean body mass administered every other week over a 52 week period for a total of 26 intravenous infusions. The primary endpoint analysis is the baseline adjusted change in HVPG at 1 year (53 55 weeks) in subjects treated with placebo as compared to subjects treated with GR MD 02 (2 mg/kg/week or 8 mg/kg/week).

An esophagogastroduodenoscopy (EGD) with evaluation for varices, HVPG, and liver biopsy will be performed before the first infusion and after the final 26th dose of IMP. Additionally, subjects will undergo a FibroScan (if available) prior to the first infusion, at Infusion Visit 13, and 14 to 28 days following final 26th infusion, an MBT (if available) will be performed at screening, at Infusion Visit 13, and 14 to 28 days after the final infusion, and blood will be collected for assessment of biomarkers.

All subjects are to attend 2 postdose visits: the first will occur 14 to 28 days after the final dose administration and a second will occur 14 days following the first postdose visit.

Subjects will be offered enrollment into a subsequent separate study, an open label extension study, if there is adequa

Detailed Summary:
Sponsor: Galectin Therapeutics Inc.

Current Primary Outcome: evaluate the efficacy of GR MD 02 on reducing hepatic venous pressure gradient (HVPG) as a measure of portal pressure compared to placebo [ Time Frame: 1 year ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • The baseline-adjusted mean change in the CPA [ Time Frame: 1 year ]
    The baseline-adjusted mean change in the CPA at 1 year as determined by digital morphometric analysis of liver biopsies
  • Proportion of subjects who have at least a one stage change in Ishak histopathological staging of fibrosis [ Time Frame: 1 year ]
    Proportion of subjects who have at least a one stage change in Ishak histopathological staging of fibrosis at 1 year as assessed on liver biopsy
  • The baseline-adjusted mean change in liver stiffness [ Time Frame: 14 to 28 days after final infusion ]
    The baseline-adjusted mean change in liver stiffness as determined by FibroScan score prior to the first infusion, at Infusion Visit 13, and 14 to 28 days after final infusion
  • The baseline-adjusted mean change in the metabolic capacity of the liver [ Time Frame: 14 to 28 days after final infusion ]
    The baseline-adjusted mean change in the metabolic capacity of the liver as determined by cPDR30 of the MBT (if available) at screening, Infusion Visit 13, and 14 to 28 days after final infusion
  • Proportion of subjects who have at least a one stage change in Brunt-Kleiner histopathological staging of fibrosis [ Time Frame: 1 year ]
    Proportion of subjects who have at least a one stage change in Brunt-Kleiner histopathological staging of fibrosis at 1 year as assessed on liver biopsy
  • The difference between GR-MD-02-treated and placebo-treated subjects in the progression of cirrhosis [ Time Frame: 1 year ]
    The difference between GR-MD-02-treated and placebo-treated subjects in the progression of cirrhosis at 1 year, defined as the development of any of the following: esophageal variceal hemorrhage or portal hypertensive gastropathy hemorrhage (confirmed by endoscopy or interventional radiology); clinically apparent ascites; spontaneous bacterial peritonitis; overt hepatic encephalopathy; an increase in Child-Turcotte-Pugh score ≥2 points; newly diagnosed varices in a subject without prior varices; progression from small to medium or large varices; qualification for liver transplant defined as a MELD score ≥15; listing for a liver transplant or the performance of a liver transplant; liver-related mortality


Original Secondary Outcome:

Information By: Galectin Therapeutics Inc.

Dates:
Date Received: June 2, 2015
Date Started: June 2015
Date Completion: February 2018
Last Updated: March 21, 2017
Last Verified: February 2017