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Study Evaluating the Safety, Efficacy, and Pharmacokinetics of Miricorilant in Participants With Presumed Nonalcoholic Steatohepatitis (NASH)

Phase 2
Terminated
Conditions
Nonalcoholic Steatohepatitis (NASH)
Interventions
Drug: Placebo
Registration Number
NCT03823703
Lead Sponsor
Corcept Therapeutics
Brief Summary

This phase 2, double blind, placebo-controlled, randomized study is to assess the safety and efficacy of miricorilant (CORT118335) in patients with presumed Nonalcoholic Steatohepatitis (NASH).

Detailed Description

This is a randomized, double-blind, placebo-controlled study that assessed the safety efficacy and pharmacokinetics (PK) of miricorilant in patients with presumed Nonalcoholic Steatohepatitis (NASH). Patients who meet the criteria for Study CORT118335-860 were randomized on Day 1 to receive 900 mg miricorilant, 600 mg miricorilant, or placebo for 12 weeks.

Due to observations related to safety, the study was terminated prior to completion and study objectives, endpoints, and procedures were modified as specified in the protocol.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
12
Inclusion Criteria
  • Have a diagnosis of NASH based on a biopsy obtained within the last year OR
  • Have a diagnosis of presumed NASH based on blood tests and scans
Exclusion Criteria
  • Have participated in another clinical trial within the last year and received active treatment for NASH
  • Have participated in another clinical trial for any other indication within the last 3 months
  • Are pregnant or lactating women
  • Have a BMI <18 kg/m^2
  • Have had liver transplantation or plan to have liver transplantation during the study
  • Have type 1 diabetes or poorly controlled type 2 diabetes.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Miricorilant- 900 mgMiricorilantParticipants received 900 mg miricorilant (6 miricorilant tablets of 150 mg) orally once daily.
PlaceboPlaceboParticipants received 6 placebo tablets orally once daily.
Miricorilant- 600 mgMiricorilantParticipants received 600 mg miricorilant (4 miricorilant tablets of 150 mg and 2 placebo tablets) orally once daily.
Miricorilant- 600 mgPlaceboParticipants received 600 mg miricorilant (4 miricorilant tablets of 150 mg and 2 placebo tablets) orally once daily.
Primary Outcome Measures
NameTimeMethod
Relative Change From Baseline in Liver Fat Content Assessed by Magnetic Resonance Imaging-Proton Density Fat FractionBaseline and up to ~Day 95

The change from baseline in liver fat content (LFC) by magnetic resonance imaging-proton density fat fraction (MRI-PDFF) for each miricorilant dose level (600 mg, 900 mg) versus placebo was assessed. MRI-PDFF was performed to determine the degree of LFC reduction. The relative change is defined for each participant as %: (\[Post-Baseline LFC-Baseline LFC\]/Baseline LFC) × 100. Due to observations related to safety, the study was terminated. If the participant had at least 6 weeks of treatment, the assessment was completed at the early termination visit. Due to the small sample size, no formal tests were performed to assess statistical differences between treatment groups.

Secondary Outcome Measures
NameTimeMethod
Number of Participants Achieving a Relative Reduction From Baseline in LFC of ≥30% by MRI-PDFFBaseline and up to ~Day 95

The number of participants (defined as responders) with a ≥30% reduction in LFC from baseline by treatment group as assessed by MRI-PDFF. The number of participants with a reduction in LFC from baseline of \<30% were defined as non-responders. MRI-PDFF was performed at screening and up to 33 days after last dose of study drug. Due to observations related to safety, the study was terminated. If the participant had at least 6 weeks of treatment, the assessment was completed at the early termination visit. Due to the small sample size, no formal tests were performed to assess statistical differences between treatment groups.

Change From Baseline in Aspartate AminotransferaseBaseline and Week 6

The change in aspartate aminotransferase (AST) from baseline for each treatment group at the Week 6 visit is summarized. Due to the small sample size, no formal tests were performed to assess statistical differences between treatment groups.

Change From Baseline in Alanine AminotransferaseBaseline and Week 6

The change in serum alanine aminotransferase (ALT) from baseline for each treatment group at the Week 6 visit is summarized. Due to the small sample size, no formal tests were performed to assess statistical differences between treatment groups.

Change From Baseline in Gamma-glutamyl TransferaseBaseline and Week 6

The change in gamma-glutamyl transferase (GGT) from baseline for each treatment group at the Week 6 visit is summarized. Due to the small sample size, no formal tests were performed to assess statistical differences between treatment groups.

Change From Baseline in Propeptide of Type III CollagenBaseline and Week 6

The change in serum propeptide of Type III collagen (pro-C3) from baseline at the Week 6 visit is summarized. Due to the small sample size, no formal tests were performed to assess statistical differences between treatment groups.

Change From Baseline in Enhanced Liver Fibrosis ScoreBaseline and Week 6

The change in enhanced liver fibrosis (ELF) from baseline for each treatment group at the Week 6 visit is summarized. The ELF score combines 3 serum biomarkers (hyaluronic acid, tissue inhibitor of metalloproteinases-1 \[TIMP-1\] and type III procollagen \[PIIINP\]) which have been shown to correlate with the degree of liver fibrosis assessed by liver biopsy. Each of these markers is measured by an immunoassay and an ELF score is generated \[ELF=2.278+0.851 ln(HA)+0.751 ln(PIIINP)+0.394 ln(TIMP-1)\], from which a level of fibrosis severity can be determined; higher ELF scores are associated with worsening liver fibrosis. Due to the small sample size, no formal tests were performed to assess statistical differences between treatment groups.

Trial Locations

Locations (15)

Site 208

🇺🇸

Glendale, Arizona, United States

Site 234

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Port Orange, Florida, United States

Site 215

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Edinburg, Texas, United States

Site 214

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Panorama City, California, United States

Site 209

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Tucson, Arizona, United States

Site 207

🇺🇸

Chandler, Arizona, United States

Site 213

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Edinburg, Texas, United States

Site 211

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Austin, Texas, United States

Site 228

🇺🇸

Kansas City, Missouri, United States

Site 227

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Los Angeles, California, United States

Site 232

🇺🇸

East Syracuse, New York, United States

Site 212

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San Antonio, Texas, United States

Site 226

🇺🇸

Seattle, Washington, United States

Site 233

🇺🇸

Santa Ana, California, United States

Site 210

🇺🇸

Sarasota, Florida, United States

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