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

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™)

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.

Study Overview

• Status: Completed
• Conditions: Non-alcoholic Fatty Liver Disease; NASH - Nonalcoholic Steatohepatitis; Non-alcoholic Steatohepatitis
• Intervention / Treatment: Drug: Placebo; Drug: MSDC-0602K

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 392
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
    • Tucson, Arizona, United States, 85712
  • California
    • Chula Vista, California, United States, 91910
    • Fresno, California, United States, 93701
    • Garden Grove, California, United States, 92844
    • Huntington Park, California, United States, 90255
    • La Mesa, California, United States, 91942
    • Los Angeles, California, United States, 90036
    • Los Angeles, California, United States, 90057
    • Poway, California, United States, 92064
    • Rialto, California, United States, 92377
    • San Diego, California, United States, 92103
  • Colorado
    • Englewood, Colorado, United States, 80113
  • Florida
    • Gainesville, Florida, United States, 32610
    • Hialeah, Florida, United States, 33016
    • Inverness, Florida, United States, 34452
    • Lakewood Ranch, Florida, United States, 34211
    • Miami Lakes, Florida, United States, 33016
    • Wellington, Florida, United States, 33414
  • Georgia
    • Marietta, Georgia, United States, 30060
  • Indiana
    • Indianapolis, Indiana, United States, 46202
  • Louisiana
    • Bastrop, Louisiana, United States, 71220
    • New Orleans, Louisiana, United States, 70112
    • New Orleans, Louisiana, United States, 70115
    • West Monroe, Louisiana, United States, 71291
  • Mississippi
    • Flowood, Mississippi, United States, 39232
  • New York
    • Brooklyn, New York, United States, 112301
    • New York, New York, United States, 10018
  • North Carolina
    • Fayetteville, North Carolina, United States, 28304
    • Greenville, North Carolina, United States, 27834
    • Statesville, North Carolina, United States, 28677
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
  • Tennessee
    • Germantown, Tennessee, United States, 38138
    • Hermitage, Tennessee, United States, 37076
  • Texas
    • Arlington, Texas, United States, 76012
    • Dallas, Texas, United States, 75203
    • Fort Sam Houston, Texas, United States, 78234
    • Houston, Texas, United States, 77030
    • Live Oak, Texas, United States, 78233
    • Rollingwood, Texas, United States, 78746
    • San Antonio, Texas, United States, 78215
    • San Antonio, Texas, United States, 78265
  • Virginia
    • Richmond, Virginia, United States, 23249

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Cirius Therapeutics, Inc.
• Collaborators: Chiltern International Inc.
• Investigators: Study Director: Howard Dittrich, MD, Cirius Therapeutics, Inc.

Publications and helpful links

General Publications

• Harrison SA, Alkhouri N, Davison BA, Sanyal A, Edwards C, Colca JR, Lee BH, Loomba R, Cusi K, Kolterman O, Cotter G, Dittrich HC. Insulin sensitizer MSDC-0602K in non-alcoholic steatohepatitis: A randomized, double-blind, placebo-controlled phase IIb study. J Hepatol. 2020 Apr;72(4):613-626. doi: 10.1016/j.jhep.2019.10.023. Epub 2019 Nov 4.

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2016
• Primary Completion (Actual): June 1, 2019
• Study Completion (Actual): June 1, 2019

Study Registration Dates

• First Submitted: May 18, 2016
• First Submitted That Met QC Criteria: May 24, 2016
• First Posted (Estimate): May 27, 2016

Study Record Updates

• Last Update Posted (Actual): September 16, 2020
• Last Update Submitted That Met QC Criteria: August 28, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: NASH
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: MSDC-0602K-C009NASH

Plan for Individual participant data (IPD)

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