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

Study Overview
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Brief Summary
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This phase 1b, Open-Label Study is to assess the safety, efficacy of miricorilant in patients with presumed Nonalcoholic Steatohepatitis (NASH)

Detailed Description
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This phase 1b, Open-Label Study will assess the safety, efficacy and pharmacokinetics (PK) of miricorilant in patients with presumed Nonalcoholic Steatohepatitis (NASH). Patients who meet the criteria for the study CORT-118335-861 will be enrolled on Day 1 into 1 of 11 cohorts and receive: Cohort 1 - a daily dose of 150 mg of miricorilant over 24 weeks. Cohort 2 - a daily dose of 150 mg of miricorilant over 12 weeks. Cohort 3 - a daily dose of 100 mg of miricorilant over 2 weeks, followed by 10 weeks of dosing at 100 mg miricorilant every Monday, Wednesday and Friday. Cohort 4 - a daily dose of 100 mg of miricorilant over 2 weeks, followed by 10 weeks of dosing at 100 mg miricorilant every Monday and Friday. Cohort 5 - a thrice weekly dose of 100 mg of miricorilant over 12 weeks every Monday, Wednesday, and Friday. Cohort 6 - a twice weekly dose of 100 mg of miricorilant over 12 weeks every Monday and Friday. Cohort 7 - a daily dose of 50 mg of miricorilant over 12 weeks. Cohort 8 - a daily dose of 100 mg of miricorilant over 12 weeks. Cohort 9 - a daily dose of 30 mg of miricorilant over 12 weeks. Cohort 10 - a once weekly dose of 200 mg of miricorilant over 12 weeks. Cohort 11 - a twice weekly dose of 150 mg miricorilant over 12 weeks.

Official Title
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A Phase 1b, Open-Label Study Evaluating the Safety, Efficacy, and Pharmacokinetics of Miricorilant in Adult Patients With Presumed Nonalcoholic Steatohepatitis (NASH)

Conditions
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Nonalcoholic Steatohepatitis (NASH)

Intervention / Treatment
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* Drug: Miricorilant 150 mg
* Drug: Miricorilant 100 mg
* Drug: Miricorilant 50 mg
* Drug: Miricorilant 10 mg


Participation Criteria
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Eligibility Criteria
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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/m2 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
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 - 150 mg of miricorilant for 24 weeks<br>Patients who meet the entry criteria for study CORT-118335-861 will be enrolled to receive miricorilant as a steady dose of 150 mg once daily, for 24 weeks. | Drug: Miricorilant 150 mg<br>* Miricorilant 150 mg for oral dosing<br>* Other names: CORT118335;|
| Experimental: Cohort 2 - 150 mg of miricorilant for 12 weeks<br>Patients who meet the entry criteria for study CORT-118335-861 will be enrolled to receive miricorilant as a steady dose of 150 mg once daily, for 12 weeks. | Drug: Miricorilant 150 mg<br>* Miricorilant 150 mg for oral dosing<br>* Other names: CORT118335;|
| Experimental: Cohort 3 - 100 mg daily miricorilant for 2 weeks, followed by 100 mg every MWF for 10 weeks<br>Patients who meet the entry criteria for study CORT-118335-861 will be enrolled to receive miricorilant as a steady dose of 100 mg once daily for 2 weeks, followed by 100 mg of miricorilant every Monday, Wednesday and Friday for 10 weeks. | Drug: Miricorilant 100 mg<br>* Miricorilant 100 mg for oral dosing<br>* Other names: CORT118335;|
| Experimental: Cohort 4 - 100 mg daily miricorilant for 2 weeks, followed by 100 mg every MF for 10 weeks<br>Patients who meet the entry criteria for study CORT-118335-861 will be enrolled to receive miricorilant as a steady dose of 100 mg once daily, for 2 weeks, followed by 100 mg of miricorilant every Monday and Friday for 10 weeks. | Drug: Miricorilant 100 mg<br>* Miricorilant 100 mg for oral dosing<br>* Other names: CORT118335;|
| Experimental: Cohort 5 - 100 mg of miricorilant every MWF for 12 weeks<br>Patients who meet the entry criteria for study CORT-118335-861 will be enrolled to receive miricorilant of 100 mg every Monday, Wednesday and Friday for 12 weeks. | Drug: Miricorilant 100 mg<br>* Miricorilant 100 mg for oral dosing<br>* Other names: CORT118335;|
| Experimental: Cohort 6 - 100 mg of miricorilant every MF for 12 weeks<br>Patients who meet the entry criteria for study CORT-118335-861 will be enrolled to receive miricorilant of 100 mg every Monday and Friday for 12 weeks. | Drug: Miricorilant 100 mg<br>* Miricorilant 100 mg for oral dosing<br>* Other names: CORT118335;|
| Experimental: Cohort 7 - 50 mg of miricorilant daily for 12 weeks<br>Patients who meet the entry criteria for study CORT-118335-861 will be enrolled to receive miricorilant as a steady dose of 50 mg once daily, for 12 weeks. | Drug: Miricorilant 50 mg<br>* Miricorilant 50 mg for oral dosing<br>* Other names: CORT118335;|
| Experimental: Cohort 8 - 100 mg of miricorilant daily for 12 weeks<br>Patients who meet the entry criteria for study CORT-118335-861 will be enrolled to receive miricorilant as a steady dose of 100 mg once daily, for 12 weeks. | Drug: Miricorilant 50 mg<br>* Miricorilant 50 mg for oral dosing<br>* Other names: CORT118335;|
| Experimental: Cohort 9 - 30 mg of miricorilant daily for 12 weeks<br>Patients who meet the entry criteria for study CORT-118335-861 will be enrolled to receive miricorilant as a steady dose of 30 mg once daily, for 12 weeks. | Drug: Miricorilant 10 mg<br>* Miricorilant 10 mg for oral dosing.<br>* Other names: CORT118335;|
| Experimental: Cohort 10 - 200 mg of miricorilant once a week for 12 weeks<br>Patients who meet the entry criteria for study CORT-118335-861 will be enrolled to receive miricorilant as a steady dose of 200 mg once weekly, for 12 weeks. | Drug: Miricorilant 50 mg<br>* Miricorilant 50 mg for oral dosing<br>* Other names: CORT118335;|
| Experimental: Cohort 11 - 150 mg of miricorilant twice weekly for 12 weeks<br>Patients who meet the entry criteria for study CORT-118335-861 will be enrolled to receive miricorilant as a steady dose of 150 mg twice weekly for 12 weeks. | Drug: Miricorilant 50 mg<br>* Miricorilant 50 mg for oral dosing<br>* Other names: CORT118335;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative change from Baseline in liver-fat content assessed by MRI-PDFF compared to Baseline. |  | Baseline Day 1 up to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in aspartate aminotransferase (AST). |  | Baseline Day 1 up to Week 24 | 
| Change from Baseline in alanine aminotransferase (ALT). |  | Baseline Day 1 up to Week 24 | 
| Change from Baseline in gamma-glutamyl transferase (GGT). |  | Baseline Day 1 up to Week 24 | 
| Change from baseline in enhanced liver fibrosis score (ELF). | ELF numerical values are calculated from serum measurements of hyaluronic acid (HA), tissue inhibitor of metalloproteinases-1 (TIMP-1), and type III procollagen (PIIINP) using the formula: ELF score = 2.494 + 0.846 In [HA] + 0.735 In [PIIINP] + 0.391 In [TIMP-1], and range on a continuous scale. Liver fibrosis is unlikely with scores <6.7 and increasingly likely with higher scores. | Baseline Day 1 up to Week 24 | 

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