A Study of MSDC-0602K to Assess Glycemic Control and Cardiovascular Outcomes in Patients With Pre-T2D or T2D and NAFLD/NASH

MMONARCh-1: Study of MSDC-0602K, a Modulator of the Mitochondrial Pyruvate Carrier for Outcomes in Patients With Pre Type 2 Diabetes (T2D) or T2D and NAFLD/NASH, Assessed for ImpRoved Glycemic Control and Cardiovascular Outcomes-1

This is a randomized, double-blind study of MSDC-0602K or placebo in subjects with pre-T2D or T2D and evidence of NAFLD/NASH.

Study Overview

• Status: Not yet recruiting
• Conditions: Type2 Diabetes; Nonalcoholic Steatohepatitis; NASH - Nonalcoholic Steatohepatitis; Non-Alcoholic Fatty Liver Disease
• Intervention / Treatment: Drug: Placebo; Drug: MSDC-0602K

Detailed Description

This is a randomized, double-blind study of MSDC-0602K or placebo given orally once daily to subjects with pre-T2D or T2D and evidence of NAFLD/NASH. Visits will include a Screening Period, a minimum Treatment of 26 weeks, and a Long-Term Follow-up Period during which subjects will continue taking assigned treatment.

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

• Study Type: Interventional
• Enrollment (Anticipated): 1800
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 comply with approved double barrier contraceptive method for the duration of the trial. Females of non-childbearing potential are considered:

   Post-menopausal Surgically sterile

4. Diagnosis of NAFLD
5. AST>27 U/L
6. HgbA1c >6%
7. Diagnosis of Pre-T2D or T2D
8. History of macrovascular cardiovascular disease

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. Estimated glomerular filtration rate (eGFR by MDRD) <30 ml/min/1.73 m2 but ≤75 ml/min/1.73 m2
10. In patients who are not anticoagulated, INR ≥ 1.3 times ULN at Screening or other evidence of impaired coagulation.
11. Acute vascular events including ACS, stroke or TIA, worsening of peripheral vascular disease or any vascular/cardiac procedure
12. Limb amputation for reason other than trauma.
13. HbA1c >10%
14. Any planned surgery or device implantation after screening
15. Ejection fraction < 35% or Heart failure with NYHA class IV
16. History of alcohol abuse or drug abuse within 6 months prior to Screening Diagnosis at any time of Type 1 diabetes.
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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: MSDC-0602K; MSDC-0602K one tablet per day taken orally	Drug: MSDC-0602K; MSDC-0602K tablet
Placebo Comparator: Placebo; Placebo one tablet per day taken orally	Drug: Placebo; Matching tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in glycosylated hemoglobin (HbA1c) from baseline to Week 26		26 weeks
Change in the weighted average of standardized AST, CK-18, and HbA1c values (standard deviations) from baseline to Week 26	This is a single composite outcome measure. This is derived by standardizing the values of AST, CK-18, and HbA1c by subtracting the respective study population means and dividing by respective study population standard deviations at each time point; averaging these standardized AST, CK-18,and HbA1c values (or z-scores) for a given patient at each time point; and then computing the difference from baseline to week 26 with respect to these averages.	26 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first event of death, adjudicated nonfatal MI or USA hospitalization, adjudicated hospital admission for HF, or adjudicated nonfatal ischemic stroke.		through study completion, an expected average of 15 months
Time to first event of death or adjudicated non-fatal MI or USA hospitalization, adjudicated hospital admission for HF, adjudicated nonfatal ischemic stroke, or liver event in all randomized subjects.	A liver event consists of ascites (confirmed by paracentesis or abdominal imaging), hepatic encephalopathy (defined clinically), variceal hemorrhage (confirmed by endoscopy), or liver transplant.	through study completion, an expected average of 15 months

Collaborators and Investigators

• Sponsor: Cirius Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2022
• Primary Completion (Anticipated): September 1, 2024
• Study Completion (Anticipated): September 1, 2024

Study Registration Dates

• First Submitted: May 29, 2019
• First Submitted That Met QC Criteria: May 29, 2019
• First Posted (Actual): May 31, 2019

Study Record Updates

• Last Update Posted (Actual): July 12, 2021
• Last Update Submitted That Met QC Criteria: July 8, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Diabetes; NAFLD; NASH
• Additional Relevant MeSH Terms: Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Liver Diseases; Diabetes Mellitus, Type 2; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: CTI-0602K-C013

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No