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A Study of MSDC-0602K to Assess Glycemic Control, Resolution of NASH, and Outcomes in Patients With Diabetes and NASH

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03970031
Recruitment Status : Not yet recruiting
First Posted : May 31, 2019
Last Update Posted : May 31, 2019
Sponsor:
Information provided by (Responsible Party):
Cirius Therapeutics, Inc.

Brief Summary:
This is a randomized, double-blind study of MSDC-0602K or placebo in subjects with type 2 diabetes and evidence of NASH.

Condition or disease Intervention/treatment Phase
Type2 Diabetes NASH - Nonalcoholic Steatohepatitis Nonalcoholic Steatohepatitis Non-Alcoholic Fatty Liver Disease Drug: MSDC-0602K Drug: Placebo oral tablet Phase 3

Detailed Description:

This is a randomized, double-blind study of MSDC-0602K or placebo given orally once daily to subjects with type 2 diabetes and evidence of NASH. Visits to the clinic will be at baseline, 1, 3, and every 3 months thereafter until the study is terminated.

Safety will be assessed by periodic measurement of vital signs, physical examinations, blood laboratory analyses, and the occurrence of adverse events.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 3600 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: MMONARCh: Study of MSDC-0602K, a Modulator of the Mitochondrial Pyruvate Carrier for Outcomes in Patients With NASH and Diabetes, Assessed for Resolution of NASH and Improved Glycemic Control
Estimated Study Start Date : September 2019
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021


Arm Intervention/treatment
Active Comparator: MSDC-0602K Tablet
MSDC-0602K Dose 1 taken one tablet per day orally
Drug: MSDC-0602K
MSDC-0602K tablets

Placebo Comparator: Placebo Tablet
Matching placebo taken one tablet per day orally
Drug: Placebo oral tablet
Placebo tablets




Primary Outcome Measures :
  1. Mean change in glycosylated hemoglobin (HbA1c) from Baseline to 6 months follow-up in the first 800 subjects randomized with poorly controlled T2D [ Time Frame: 6 months ]
    Mean change in glycosylated hemoglobin (HbA1c) from Baseline (Baseline HbA1c is defined as the average of HbA1c values from Screening 2 and Randomization) to 6 months follow-up in the first 800 subjects randomized in the stratum of poorly controlled T2D (defined as average Screening HbA1c > 7.0%) with baseline (average Screening 2 and Randomization) HbA1c > 7.0% who have reached 6-month follow-up.

  2. Biopsy-confirmed hepatic histological resolution of NASH as evidenced by ALL of the following at 12 months: o Inflammation score of 0-1; o Ballooning score of 0; o At least a 2-point improvement (decrease) in the NAS; and o NO worsening of fibrosis [ Time Frame: 12 months ]

    Biopsy-confirmed hepatic histological resolution of NASH as evidenced by ALL of the following at 12 months:

    • Inflammation score of 0-1;
    • Ballooning score of 0;
    • At least a 2-point improvement (decrease) in the NAS; and
    • No worsening of fibrosis defined as no increase in CRN fibrosis score

    in the first 1000 subjects randomized into the NASH histology stratum with NASH criteria confirmed by central histopathology.



Secondary Outcome Measures :
  1. Time to first event of Death or Hepatic and/or Major Adverse Cardiac Events [ Time Frame: 31 months ]
    Time to first event of Death or Hepatic and/or Major Adverse Cardiac Events in all randomized subjects



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  1. Written informed consent.
  2. Adult subjects with an age of > 18 years but < 80 years.
  3. Male or female subjects with reproductive potential must agree to use a highly effective method of contraception for the duration of the trial. Females of non-childbearing potential are considered:

    • Post-menopausal
    • Surgically sterile
  4. Evidence of NASH with fibrosis
  5. HgbA1c >6%
  6. Diagnosis of T2D diagnosis
  7. History of macrovascular cardiovascular disease
  8. Estimated glomerular filtration rate (eGFR by MDRD) ≥30 ml/min/1.73 m2 but ≤75 ml/min/1.73 m2

Biopsy Subgroup only:

  1. Histologically-defined NASH on a baseline liver biopsy done within 4 months.
  2. No more than 5% change in body weight between the time of qualifying biopsy and Screening 1.

Key Exclusion Criteria:

  1. Prior liver transplantation or currently on transplant list.
  2. Other well-documented causes of active chronic liver disease
  3. Current cirrhosis
  4. Pregnant or nursing women
  5. AST or ALT > 5 times the upper limit of normal
  6. Total bilirubin > 1.3 mg/dL unless diagnosis of Gilbert's disease with direct bilirubin within normal reference range
  7. Serum albumin < 3.5 g/dL at Screening
  8. Alkaline phosphatase >2 times the upper limit of normal at Screening
  9. In patients who are not anticoagulated, INR ≥ 1.3 times ULN at Screening or other evidence of impaired coagulation.
  10. Acute vascular events including ACS, stroke or TIA, worsening of peripheral vascular disease or any vascular/cardiac procedure
  11. Limb amputation for reason other than trauma.
  12. HbA1c >10%
  13. Any planned surgery or device implantation after screening
  14. Ejection fraction < 35% or Heart failure with NYHA class IV
  15. History of alcohol abuse or drug abuse within 6 months prior to Screening
  16. Diagnosis at any time of Type 1 diabetes mellitus.
  17. Current or history of recent (≤ 6 months) use of ursodeoxycholic acid.
  18. Current use of insulin.
  19. Current use of thiazolidinediones.
  20. Any history or current concomitant disorder such as haematological, pulmonary, metabolic, endocrine disorders that are severe or life-threatening.
  21. Use of concomitant medications with a known significant metabolism by CYP2C8 including paclitaxel or repaglinide for the duration of the study.
  22. History of diabetic ketoacidosis or hyperosmolar non-ketotic coma within the 6 months prior to Screening.
  23. Known or suspected intolerance or hypersensitivity to the study drugs, closely related compounds such as PPARγ agonists (pioglitazone or rosiglitazone), or any of their stated ingredients.
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Responsible Party: Cirius Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03970031    
Other Study ID Numbers: CTI-0602K-C013
First Posted: May 31, 2019    Key Record Dates
Last Update Posted: May 31, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Cirius Therapeutics, Inc.:
Diabetes
NASH
Additional relevant MeSH terms:
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Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Digestive System Diseases