A Phase 2, Double-Blind (DB), Randomized, Placebo-Controlled Study Followed by an Open-Label Extension Period to Evaluate the Activity of Seladelpar in Subjects with Nonalcoholic Steatohepatitis (NASH) OLE phase was not analyzed due to the early termination of the study
Primary Objectives 1. To evaluate the effect of seladelpar on hepatic fat fraction, as assessed by magnetic resonance imaging-proton density fat fraction (MRI-PDFF) at Week 12 in the DB phase 2. To evaluate the safety and tolerability of seladelpar in the DB and OLE phases Secondary Objectives 1. To evaluate the effect of seladelpar on MRI- PDFF at Week 26 and Week 52 in the DB phase 2. To evaluate the effect of seladelpar on histological improvement of nonalcoholic fatty liver disease activity score (NAS) at Week 52 in the DB phase 3. To evaluate the effect of seladelpar on histological improvement of fibrosis at Week 52 in the DB phase 4. To evaluate the effect of seladelpar on metabolic biochemical markers and biochemical markers of inflammation in the DB and OLE phases
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
181
10 mg, 20 mg, or 50 mg
Matching placebo Capsule
CymaBay Research Site
Glendale, Arizona, United States
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Tucson, Arizona, United States
CymaBay Research Site
Los Angeles, California, United States
Percentage Change From Baseline in Magnetic Resonance Imaging-proton Density Fat Fraction (MRI-PDFF)
Evaluate the effect of seladelpar on hepatic fat fraction, as assessed by magnetic resonance imaging-proton density fat fraction (MRI-PDFF) at Week 12 in the double-blind (DB) phase. MRI-PDFF Relative (Percent) Change From Baseline to Week 12 - ANCOVA - mITT Population MRI-PDFF exam was used to quantify the hepatic proton density fat fraction noninvasively. The fat fraction is the proportion of mobile protons in liver tissue attributable to fat and thus, is a noninvasive magnetic resonance-based biomarker of liver triglyceride concentration.
Time frame: Week 12
Percentage of Participants With Improvement of 2 Points or More in the Nonalcoholic Fatty Liver Disease Activity Score (NAS)
Histopathology nonalcoholic fatty liver disease activity score (NAS) change from baseline ≤-2 (Improvements of 2 points or more in NAS) - mITT Population Total NAS score represents the sum of scores for steatosis, lobular inflammation, and ballooning, and ranges from 0-8. Diagnosis of NASH (or, alternatively, fatty liver not diagnostic of NASH) should be made first, then NAS is used to grade activity. NAS scores of 0-2 occurred in cases largely considered not diagnostic of NASH, scores of 3-4 were evenly divided among those considered not diagnostic, borderline, or positive for NASH. Scores of 5-8 occurred in cases that were largely considered diagnostic of NASH
Time frame: Week 52
Percent Change From Baseline in Alanine Aminotransferase (ALT) at Week 12 and Week 52
Alanine Aminotransferase (ALT) Relative (percent) change of from Baseline to Weeks 12 and Week 52 - mITT Population A decreased serum levels of alanine aminotransferase (ALT) is a marker of liver function improvement.
Time frame: Week 12, Week 52
Percent Change From Baseline in Aspartate Aminotransferase (AST) at Week 12 and Week 52
Relative (Percent) Change of Aspartate Aminotransferase (AST) From Baseline to Weeks 12 and Week 52 - mITT Population A decreased serum levels of Aspartate Aminotransferase (AST) is a marker of liver function improvement.
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CymaBay Research Site
Boca Raton, Florida, United States
CymaBay Research Site
Lakewood Rch, Florida, United States
CymaBay Research Site
Flowood, Mississippi, United States
CymaBay Research Site
Clarksville, Tennessee, United States
CymaBay Research Site
Germantown, Tennessee, United States
CymaBay Research Site
Hermitage, Tennessee, United States
CymaBay Research Site
Knoxville, Tennessee, United States
...and 4 more locations
Time frame: Weeks 12, Week 52
Percent Change From Baseline in Gamma Glutamyl Transferase (GGT) at Week 12 and Week 52
Relative (Percent) Change of Gamma Glutamyl Transferase (GGT) From Baseline to Weeks 12 and Week 52 - mITT Population A decreased serum levels of Gamma Glutamyl Transferase (GGT) is a marker of liver function improvement.
Time frame: Weeks 12, Week 52
Number of Participants With Decrease in MRI-PDFF ≥ 30% From Baseline at Week 12 and Week 52
Number of Participants with a relative decrease in MRI-PDFF ≥30% (ie, percent change ≥ 30%) at Weeks 12, and 52/ET (Early Termination) in the DB phase - mITT Population. MRI-PDFF exam was used to quantify the hepatic proton density fat fraction noninvasively. The fat fraction is the proportion of mobile protons in liver tissue attributable to fat and thus, is a noninvasive magnetic resonance-based biomarker of liver triglyceride concentration. MRI-PDFF response defined as ≥30% relative decline in MRI-PDFF is associated with ≥1 stage improvement in fibrosis and may be used as a surrogate marker of fibrosis regression in early phase clinical trials for NASH
Time frame: Week 12, Week 52
Percentage Change From Baseline in Magnetic Resonance Imaging-proton Density Fat Fraction (MRI-PDFF) at Week 52
Percentage Change from Baseline in MRI-PDFF to Weeks 52//ET - mITT Population MRI-PDFF exam was used to quantify the hepatic proton density fat fraction noninvasively. The fat fraction is the proportion of mobile protons in liver tissue attributable to fat and thus, is a noninvasive magnetic resonance-based biomarker of liver triglyceride concentration.
Time frame: Week 52
Number of Liver Biopsy Responders With Reversal of NASH Reversal of NASH (Ballooning Score of 0 and Lobular Inflammation Score of 0 or 1) and no Worsening of Hepatic Fibrosis at Week 52
Liver Biopsy Responders with reversal of NASH (ballooning score of 0 and lobular inflammation score of 0 or 1 and no worsening of hepatic fibrosis) at Week 52/ET. The reversal of NASH was defined as the absence of hepatocellular ballooning (score of 0) and no or minimal inflammation (lobular inflammation score of 0 or 1).
Time frame: Week 52
Percentage of Participants With Improvement by at Least 1 Stage in Fibrosis From Baseline at Week 12 and Week 52
Proportion of subjects with improvement by at least 1 stage in fibrosis without worsening of NASH (ie, improvement by at least 1 fibrosis stage without worsening of NAS) at Week 52/ET - Cochran-Mantel-Haenszel - mITTb Population There five liver fibrosis stages (F0: no scarring (no fibrosis); F1: minimal scarring; F2: scarring has occurred and extends outside the liver area (significant fibrosis); F3: fibrosis spreading and forming bridges with other fibrotic liver areas (severe fibrosis); F4: cirrhosis or advanced scarring)
Time frame: Week 52