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

Phase 2

Completed

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

Interventions: Drug: MSDC-0602K
Drug: Placebo

Registration Number: NCT02784444

Lead Sponsor: Cirius Therapeutics, Inc.

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.

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).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 392

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MSDC-0602K Dose 3 capsules	MSDC-0602K	MSDC-0602K Dose 3 capsules taken once daily for 360 days
Placebo capsules	Placebo	Matching Placebo capsule taken once daily for 360 days
MSDC-0602K Dose 2 capsules	MSDC-0602K	MSDC-0602K Dose 2 capsules taken once daily for 360 days
MSDC-0602K Dose 1 capsules	MSDC-0602K	MSDC-0602K Dose 1 capsule taken once daily for 360 days

Primary Outcome Measures

Name	Time	Method
Number of Participants With Hepatic Histological Improvement in NAS	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

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