A Study to Evaluate the Safety, Tolerability & Efficacy of MSDC-0602K in Patients With NASH

Study Overview
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Brief Summary
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This is a randomized, double-blinded study of three doses of MSDC-0602K or placebo given orally once daily to subjects with biopsy proven NASH with fibrosis and no cirrhosis.

Detailed Description
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This is a randomized, double-blinded study of three doses of MSDC-0602K or placebo given orally once daily to subjects with biopsy proven NASH with fibrosis and no cirrhosis. Visits to the clinic will be at baseline, 1, 2, 3, 6, 9, and 12 months, with one 2- week follow-up visit. Safety will be assessed by monitoring of vital signs, 12 lead electrocardiogram (ECG), physical examinations, safety labs, and adverse events (AEs).

Official Title
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A Phase 2, Randomized, Double-Blind, Placebo-Controlled, 12-Month, Multiple-Dose Study to Evaluate the Safety, Tolerability and Efficacy of Three Dose Levels of MSDC-0602K in Patients With NASH (EMMINENCE™)

Conditions
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Non-alcoholic Fatty Liver Disease, Non-alcoholic Steatohepatitis, NASH - Nonalcoholic Steatohepatitis

Intervention / Treatment
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* Drug: MSDC-0602K
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Selected Inclusion Criteria: Adult subjects 18 years of age or greater Histological evidence of NASH, based on biopsy, with a NAS (NASH CRN scoring) ≥ 4 with a score of at least 1 in each component of NAS. Histological evidence of liver fibrosis defined as NASH CRN System fibrosis score F1 to F3. Subjects with type 2 diabetes mellitus (DM) must be under stable and reasonable control. Male and female subjects who are taking Vitamin E should be on a stable dose of Vitamin E (if ≥ 400 IU) for a period of at least 3 months prior to randomization. Females should be either postmenopausal (at least 12 months since last menses) or surgically sterilized (bilateral tubal ligation or hysterectomy). Males with female partners of child-bearing potential must agree to use adequate contraceptive methods (including a condom, plus one other form of contraception) if engaging in sexual intercourse. Willing and able to sign an informed consent document indicating understanding the purpose of and procedures required for the study and willingness to participate in the study. Selected Exclusion Criteria: Known history of HIV. Prior liver transplantation. Other well-documented causes of active chronic liver disease. History of cirrhosis and/or hepatic decompensation including ascites, hepatic encephalopathy or variceal bleeding. History of alcohol abuse or drug abuse within 6 months of Screening. Type 1 diabetes mellitus. Current or history of recent (≤ 6 months) use of ursodeoxycholic acid. Use of concomitant medications with a known significant metabolism by CYP2C8 or CPY2C9. History of diabetic ketoacidosis or hyperosmolar non-ketotic coma within 6 months prior to randomization. History of heart failure (including CHF) or previous cardiovascular event (myocardial infarct, by-pass surgery, or PTCA) within the past 6 months prior to randomization. Blood pressure greater than 160/100 mmHg. Participation in an investigational study or received an investigational drug within 30 days or 5 half-lives (whichever is longer) prior to study drug administration. Malignancy, including leukemia and lymphoma (excluding basal cell and squamous skin cell cancers and localized prostrate cancer) treated within the last 2 years.

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: MSDC-0602K Dose 1 capsules<br>MSDC-0602K Dose 1 capsule taken once daily for 360 days | Drug: MSDC-0602K<br>* MSDC-0602K capsules<br>|
| Active Comparator: MSDC-0602K Dose 2 capsules<br>MSDC-0602K Dose 2 capsules taken once daily for 360 days | Drug: MSDC-0602K<br>* MSDC-0602K capsules<br>|
| Active Comparator: MSDC-0602K Dose 3 capsules<br>MSDC-0602K Dose 3 capsules taken once daily for 360 days | Drug: MSDC-0602K<br>* MSDC-0602K capsules<br>|
| Placebo Comparator: Placebo capsules<br>Matching Placebo capsule taken once daily for 360 days | Drug: Placebo<br>* Placebo capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Hepatic Histological Improvement in NAS | A decrease of at least 2 points in NAS at 12 months. At least a 1 point reduction in either ballooning or inflammation from baseline to 12 months. no increase in CRN fibrosis score (i.e., an increase of 1 stage or more) from baseline to 12 months. | 12 months (360 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Resolution of NASH With no Worsening of Fibrosis at 12 Months. | CRN ballooning score of 0 at 12-months CRN inflammation score of 0 or 1 at 12-months No increase in CRN fibrosis score from baseline to 12-months | 12 months (360 days) | 
| Number of Subjects With Improvement of Fibrosis (CRN Staging Score) by at Least 1 Stage With no Worsening of NASH at 12 Months. | Decrease in fibrosis CRN staging score of >= 1 full stage from baseline to 12 months No increase in ballooning CRN score from baseline to 12 months No increase in inflammation CRN score from baseline to 12-months | 12 months (360 days) | 
| Mean Change From Baseline in NAFLD Activity Score (NAS) | NAS is the sum of the scores of steatosis, inflammation, and ballooning. It has a range of 0 to 8 with higher scores indicating worse disease severity. | 12 months (360 days) | 
| Mean Change From Baseline in CRN Steatosis Score | Steatosis is assessed on a scale of 0 to 3 with higher scores indicating more severe steatosis. | 12 months (360 days) | 
| Mean Change From Baseline in CRN Inflammation Score | Inflammation is assessed on a scale of 0 to 3 with higher scores indicating more severe inflammation. | 12 months (360 days) | 
| Mean Change From Baseline in CRN Ballooning Score | Hepatocellular ballooning is assessed on a scale of 0 to 2 with higher scores indicating more severe hepatocellular ballooning. | 12 months (360 days) | 
| Mean Change From Baseline in CRN Fibrosis Staging Score | Fibrosis is assessed on a scale of 0 to 4 with higher scores indicating more severe fibrosis. | 12 months (360 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NASH