Clinical trial NCT02784444: A Study to Evaluate the Safety, Tolerability & Efficacy of MSDC-0602K in Patients With NASH
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™)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-alcoholic Fatty Liver Disease
Non-alcoholic Steatohepatitis
NASH - Nonalcoholic Steatohepatitis
Keywords: NASH
Lead sponsor: Cirius Therapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Chiltern International Inc.
First posted: 2016-05-27
Enrollment: 392
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility 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.

Primary outcomes:
measure: Number of Participants With Hepatic Histological Improvement in NAS
timeFrame: 12 months (360 days)
Secondary outcomes:
measure: Number of Subjects With Resolution of NASH With no Worsening of Fibrosis at 12 Months.
timeFrame: 12 months (360 days)
measure: Number of Subjects With Improvement of Fibrosis (CRN Staging Score) by at Least 1 Stage With no Worsening of NASH at 12 Months.
timeFrame: 12 months (360 days)
measure: Mean Change From Baseline in NAFLD Activity Score (NAS)
timeFrame: 12 months (360 days)
measure: Mean Change From Baseline in CRN Steatosis Score
timeFrame: 12 months (360 days)
measure: Mean Change From Baseline in CRN Inflammation Score
timeFrame: 12 months (360 days)
measure: Mean Change From Baseline in CRN Ballooning Score
timeFrame: 12 months (360 days)
measure: Mean Change From Baseline in CRN Fibrosis Staging Score
timeFrame: 12 months (360 days)
Other outcomes:
Locations:
city: Chandler
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Chula Vista
country: United States
state: California
city: Fresno
country: United States
state: California
city: Garden Grove
country: United States
state: California
city: Huntington Park
country: United States
state: California
city: La Mesa
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Poway
country: United States
state: California
city: Rialto
country: United States
state: California
city: San Diego
country: United States
state: California
city: Englewood
country: United States
state: Colorado
city: Gainesville
country: United States
state: Florida
city: Hialeah
country: United States
state: Florida
city: Inverness
country: United States
state: Florida
city: Lakewood Ranch
country: United States
state: Florida
city: Miami Lakes
country: United States
state: Florida
city: Wellington
country: United States
state: Florida
city: Marietta
country: United States
state: Georgia
city: Indianapolis
country: United States
state: Indiana
city: Bastrop
country: United States
state: Louisiana
city: New Orleans
country: United States
state: Louisiana
city: New Orleans
country: United States
state: Louisiana
city: West Monroe
country: United States
state: Louisiana
city: Flowood
country: United States
state: Mississippi
city: Brooklyn
country: United States
state: New York
city: New York
country: United States
state: New York
city: Fayetteville
country: United States
state: North Carolina
city: Greenville
country: United States
state: North Carolina
city: Statesville
country: United States
state: North Carolina
city: Providence
country: United States
state: Rhode Island
city: Germantown
country: United States
state: Tennessee
city: Hermitage
country: United States
state: Tennessee
city: Arlington
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Fort Sam Houston
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Live Oak
country: United States
state: Texas
city: Rollingwood
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Richmond
country: United States
state: Virginia
Study officials:
affiliation: Cirius Therapeutics, Inc.
name: Howard Dittrich, MD
role: STUDY_DIRECTOR
References:
citation: 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.