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

Study Overview
=================
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.

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

Conditions
-----------------
Nonalcoholic Steatohepatitis (NASH)

Intervention / Treatment
-----------------
* Drug: Miricorilant
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Miricorilant- 900 mg<br>Participants received 900 mg miricorilant (6 miricorilant tablets of 150 mg) orally once daily. | Drug: Miricorilant<br>* Tablets taken orally<br>* Other names: CORT118335;|
| Experimental: Miricorilant- 600 mg<br>Participants received 600 mg miricorilant (4 miricorilant tablets of 150 mg and 2 placebo tablets) orally once daily. | Drug: Miricorilant<br>* Tablets taken orally<br>* Other names: CORT118335;Drug: Placebo<br>* Placebo tablets<br>|
| Placebo Comparator: Placebo<br>Participants received 6 placebo tablets orally once daily. | Drug: Placebo<br>* Placebo tablets<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Nonalcoholic Steatohepatitis, NASH, Nonalcoholic Fatty Liver Disease