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

A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety, Efficacy, and Pharmacokinetics of Miricorilant in Patients With Presumed Nonalcoholic Steatohepatitis (NASH)

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).

Study Overview

• Status: Terminated
• Conditions: Nonalcoholic Steatohepatitis (NASH)
• Intervention / Treatment: Drug: Placebo; Drug: Miricorilant

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Site 207
    • Glendale, Arizona, United States, 85306
      • Site 208
    • Tucson, Arizona, United States, 85712
      • Site 209
  • California
    • Los Angeles, California, United States, 90057
      • Site 227
    • Panorama City, California, United States, 91402
      • Site 214
    • Santa Ana, California, United States, 92704
      • Site 233
  • Florida
    • Port Orange, Florida, United States, 32127
      • Site 234
    • Sarasota, Florida, United States, 34240
      • Site 210
  • Missouri
    • Kansas City, Missouri, United States, 61434
      • Site 228
  • New York
    • East Syracuse, New York, United States, 13057
      • Site 232
  • Texas
    • Austin, Texas, United States, 78757
      • Site 211
    • Edinburg, Texas, United States, 78539
      • Site 213
    • Edinburg, Texas, United States, 78539
      • Site 215
    • San Antonio, Texas, United States, 78229
      • Site 212
  • Washington
    • Seattle, Washington, United States, 98105
      • Site 226

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Miricorilant- 900 mg; Participants received 900 mg miricorilant (6 miricorilant tablets of 150 mg) orally once daily.	Drug: Miricorilant; Tablets taken orally; Other Names: CORT118335
EXPERIMENTAL: Miricorilant- 600 mg; Participants received 600 mg miricorilant (4 miricorilant tablets of 150 mg and 2 placebo tablets) orally once daily.	Drug: Placebo; Placebo tablets; Drug: Miricorilant; Tablets taken orally; Other Names: CORT118335
PLACEBO_COMPARATOR: Placebo; Participants received 6 placebo tablets orally once daily.	Drug: Placebo; Placebo tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative Change From Baseline in Liver Fat Content Assessed by Magnetic Resonance Imaging-Proton Density Fat Fraction	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.	Baseline and up to ~Day 95

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Achieving a Relative Reduction From Baseline in LFC of ≥30% by MRI-PDFF	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.	Baseline and up to ~Day 95
Change From Baseline in Aspartate Aminotransferase	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.	Baseline and Week 6
Change From Baseline in Alanine Aminotransferase	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.	Baseline and Week 6
Change From Baseline in Gamma-glutamyl Transferase	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.	Baseline and Week 6
Change From Baseline in Propeptide of Type III Collagen	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.	Baseline and Week 6
Change From Baseline in Enhanced Liver Fibrosis Score	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.	Baseline and Week 6

Other Outcome Measures

Outcome Measure	Time Frame
Number of Participants With a Relative Reduction in Liver Fat Content ≥50% by Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF) for Miricorilant Versus Placebo	Baseline and up to ~Day 95
Number of Participants With Complete Resolution in Liver Fat by MRI-PDFF for Miricorilant Versus Placebo	Baseline and up to ~Day 95

Collaborators and Investigators

• Sponsor: Corcept Therapeutics
• Investigators: Study Director: Director, Corcept Therapeutics

Publications and helpful links

Helpful Links

• Poster #:LP34

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 4, 2020
• Primary Completion (ACTUAL): April 5, 2021
• Study Completion (ACTUAL): April 5, 2021

Study Registration Dates

• First Submitted: January 14, 2019
• First Submitted That Met QC Criteria: January 29, 2019
• First Posted (ACTUAL): January 30, 2019

Study Record Updates

• Last Update Posted (ACTUAL): August 31, 2022
• Last Update Submitted That Met QC Criteria: August 10, 2022
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Nonalcoholic Steatohepatitis; NASH; Nonalcoholic Fatty Liver Disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: CORT118335-860

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No