Randomized, double-blind, parallel-group, multicenter study to assess efficacy, safety, and tolerability of oral tropifexor \& licogliflozin combination therapy and each monotherapy, compared with placebo for treatment of adult patients with nonalcoholic steatohepatitis (NASH) and liver fibrosis.
The study consisted of 1) a screening period, 2) a treatment period starting from randomization on Day 0 and running to Week 48, and 3) a follow-up period of 4 weeks after the last dose of study treatment. The study duration from first dose of study medication was 52 weeks.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
234
100mcg+30mcg+10mcg capsules of tropifexor taken orally every day until the 140 mcg capsule of tropifexor taken orally every day is produced, then patients will switch to the single 140mcg capsule taken orally every day
30mg tablet of licoglifozin taken orally every day
licogliflozin placebo + tropifexor placebo
Histological Improvement: Number and Percentage of Participants Who Responded at Week 48 Compared With Baseline
Response was defined as at least a one-stage improvement in fibrosis without worsening of nonalcoholic steatohepatitis (NASH) Fibrosis staging and Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) based on steatosis, lobular inflammation, and hepatocyte ballooning assessment were determined by a Study Central Reader. NASH CRN fibrosis criteria: Stage 0 = no fibrosis; Stage 1 = centrilobular pericellular fibrosis (or periportal fibrosis in children); Stage 2 = centrilobular and periportal fibrosis; Stage 3 = bridging fibrosis; and Stage 4 = cirrhosis.
Time frame: Baseline, Week 48
Number and Percentage of Participants With Resolution of NASH and no Worsening of Fibrosis
Fibrosis staging and Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) based on steatosis, lobular inflammation, and hepatocyte ballooning assessment were determined by a Study Central Reader. NASH CRN fibrosis criteria: Stage 0 = no fibrosis; Stage 1 = centrilobular pericellular fibrosis (or periportal fibrosis in children); Stage 2 = centrilobular and periportal fibrosis; Stage 3 = bridging fibrosis; and Stage 4 = cirrhosis.
Time frame: 48 weeks
Number and Percentage of Participants Who Achieved Resolution of NASH and no Worsening of Fibrosis OR Improvement in Fibrosis by at Least One Stage Without Worsening of NASH
Fibrosis staging and Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) based on steatosis, lobular inflammation, and hepatocyte ballooning assessment were determined by a Study Central Reader. NASH CRN fibrosis criteria: Stage 0 = no fibrosis; Stage 1 = centrilobular pericellular fibrosis (or periportal fibrosis in children); Stage 2 = centrilobular and periportal fibrosis; Stage 3 = bridging fibrosis; and Stage 4 = cirrhosis.
Time frame: 48 weeks
Number and Percentage of Participants With at Least One Stage Improvement in Fibrosis
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Gut PC Digestive Health Specialist
Dothan, Alabama, United States
Southern California Research Center
Coronado, California, United States
Velocity Clinical Trials
Los Angeles, California, United States
California Liver Research Institute
Pasadena, California, United States
Medical Associates Research Group
San Diego, California, United States
San fernando Valley Health Institute
Van Nuys, California, United States
Island View Gastroenterology Associates
Ventura, California, United States
Integrity Clinical Rsh LLC
Doral, Florida, United States
Galenus Group
Lehigh Acres, Florida, United States
Genoma Research Group Inc
Miami, Florida, United States
...and 70 more locations
Fibrosis staging and Nonalcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) based on steatosis, lobular inflammation, and hepatocyte ballooning assessment were determined by a Study Central Reader. NASH CRN fibrosis criteria: Stage 0 = no fibrosis; Stage 1 = centrilobular pericellular fibrosis (or periportal fibrosis in children); Stage 2 = centrilobular and periportal fibrosis; Stage 3 = bridging fibrosis; and Stage 4 = cirrhosis.
Time frame: 48 weeks
Number and Percentage of Participants With at Least Two Stage Improvement in Fibrosis Without Worsening of NASH
Fibrosis staging and Non-alcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) based on steatosis, lobular inflammation, and hepatocyte ballooning assessment were determined by a Study Central Reader. NASH CRN fibrosis criteria: Stage 0 = no fibrosis; Stage 1 = centrilobular pericellular fibrosis (or periportal fibrosis in children); Stage 2 = centrilobular and periportal fibrosis; Stage 3 = bridging fibrosis; and Stage 4 = cirrhosis.
Time frame: 48 weeks
Number and Percentage of Participants Achieving 5% or More Reduction in Body Weight at Week 48 Compared With Baseline
Whether the participants had 5% or more reduction in body weight.
Time frame: Baseline, Week 48
Change From Baseline to Week 48 in Percent Liver Fat Content Based on Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI - PDFF)
Change in liver fat content based on MRI-PDFF.
Time frame: Baseline, Week 48
Change From Baseline in Alanine Transaminase (ALT) Over Time
To determine the relationship of investigational treatment and markers of hepatic inflammation in NASH.
Time frame: Baseline to Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, follow-up (up to 62 weeks)
Change From Baseline in Aspartate Aminotransferase (AST) Over Time
To determine the relationship of investigational treatment and markers of hepatic inflammation in NASH.
Time frame: Baseline to Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, follow-up (up to 62 weeks)
Change From Baseline in Gamma-glutamyltransferase (GGT) Over Time
To determine the relationship of investigational treatment and markers of hepatic inflammation in NASH.
Time frame: Baseline to Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, follow-up (up to 62 weeks)