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

• ClinicalTrials.gov Identifier: NCT02784444
• Recruitment Status: Completed
• First Posted: May 27, 2016
• Results First Posted: August 21, 2020
• Last Update Posted: September 16, 2020
• Sponsor: Cirius Therapeutics, Inc.
• Collaborator: Chiltern International Inc.
• Information provided by (Responsible Party): Cirius Therapeutics, Inc.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Non-alcoholic Fatty Liver Disease; Non-alcoholic Steatohepatitis; NASH - Nonalcoholic Steatohepatitis	Drug: MSDC-0602K; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 392 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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™)
• Actual Study Start Date: September 14, 2016
• Actual Primary Completion Date: June 2019
• Actual Study Completion Date: June 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Hepatic Histological Improvement in NAS [ Time Frame: 12 months (360 days) ]
   • 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.

Secondary Outcome Measures :

1. Number of Subjects With Resolution of NASH With no Worsening of Fibrosis at 12 Months. [ Time Frame: 12 months (360 days) ]
   • 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
2. Number of Subjects With Improvement of Fibrosis (CRN Staging Score) by at Least 1 Stage With no Worsening of NASH at 12 Months. [ Time Frame: 12 months (360 days) ]
   • 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
3. Mean Change From Baseline in NAFLD Activity Score (NAS) [ Time Frame: 12 months (360 days) ]
   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.
4. Mean Change From Baseline in CRN Steatosis Score [ Time Frame: 12 months (360 days) ]
   Steatosis is assessed on a scale of 0 to 3 with higher scores indicating more severe steatosis.
5. Mean Change From Baseline in CRN Inflammation Score [ Time Frame: 12 months (360 days) ]
   Inflammation is assessed on a scale of 0 to 3 with higher scores indicating more severe inflammation.
6. Mean Change From Baseline in CRN Ballooning Score [ Time Frame: 12 months (360 days) ]
   Hepatocellular ballooning is assessed on a scale of 0 to 2 with higher scores indicating more severe hepatocellular ballooning.
7. Mean Change From Baseline in CRN Fibrosis Staging Score [ Time Frame: 12 months (360 days) ]
   Fibrosis is assessed on a scale of 0 to 4 with higher scores indicating more severe fibrosis.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Arizona

Chandler, Arizona, United States, 85224

Tucson, Arizona, United States, 85712

United States, 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

United States, Colorado

Englewood, Colorado, United States, 80113

United States, 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

United States, Georgia

Marietta, Georgia, United States, 30060

United States, Indiana

Indianapolis, Indiana, United States, 46202

United States, Louisiana

Bastrop, Louisiana, United States, 71220

New Orleans, Louisiana, United States, 70112

New Orleans, Louisiana, United States, 70115

West Monroe, Louisiana, United States, 71291

United States, Mississippi

Flowood, Mississippi, United States, 39232

United States, New York

Brooklyn, New York, United States, 112301

New York, New York, United States, 10018

United States, North Carolina

Fayetteville, North Carolina, United States, 28304

Greenville, North Carolina, United States, 27834

Statesville, North Carolina, United States, 28677

United States, Rhode Island

Providence, Rhode Island, United States, 02905

United States, Tennessee

Germantown, Tennessee, United States, 38138

Hermitage, Tennessee, United States, 37076

United States, 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

United States, Virginia

Richmond, Virginia, United States, 23249

Sponsors and Collaborators

Cirius Therapeutics, Inc.

Chiltern International Inc.

Investigators

• Study Director: Howard Dittrich, MD; Cirius Therapeutics, Inc.

  Study Documents (Full-Text)

Documents provided by Cirius Therapeutics, Inc.:

Study Protocol  [PDF] July 31, 2017

Statistical Analysis Plan  [PDF] May 16, 2019

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Cirius Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT02784444
• Other Study ID Numbers: MSDC-0602K-C009NASH
• First Posted: May 27, 2016
• Results First Posted: August 21, 2020
• Last Update Posted: September 16, 2020
• Last Verified: August 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Cirius Therapeutics, Inc.:

NASH

Additional relevant MeSH terms:

Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Digestive System Diseases