Back to resultsA Study of MSDC-0602K to Assess Glycemic Control and Cardiovascular Outcomes in Patients With Pre-T2D or T2D and NAFLD/NASH
Primary Purpose
Type2 Diabetes, NASH - Nonalcoholic Steatohepatitis, Nonalcoholic Steatohepatitis
Status
Not yet recruiting
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
MSDC-0602K
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Type2 Diabetes focused on measuring Diabetes, NASH, NAFLD
Eligibility Criteria
Key Inclusion Criteria:
- Written informed consent.
- Adult subjects with an age of > 18 years but < 80 years.
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
- Diagnosis of NAFLD
- AST>27 U/L
- HgbA1c >6%
- Diagnosis of Pre-T2D or T2D
- History of macrovascular cardiovascular disease
Key Exclusion Criteria:
- Prior liver transplantation or currently on transplant list.
- Other well-documented causes of active chronic liver disease
- Current cirrhosis
- Pregnant or nursing women
- AST or ALT > 5 times the upper limit of normal
- Total bilirubin > 1.3 mg/dL unless diagnosis of Gilbert's disease with direct bilirubin within normal reference range
- Serum albumin < 3.5 g/dL at Screening
- Alkaline phosphatase >2 times the upper limit of normal at Screening
- Estimated glomerular filtration rate (eGFR by MDRD) <30 ml/min/1.73 m2 but ≤75 ml/min/1.73 m2
- In patients who are not anticoagulated, INR ≥ 1.3 times ULN at Screening or other evidence of impaired coagulation.
- Acute vascular events including ACS, stroke or TIA, worsening of peripheral vascular disease or any vascular/cardiac procedure
- Limb amputation for reason other than trauma.
- HbA1c >10%
- Any planned surgery or device implantation after screening
- Ejection fraction < 35% or Heart failure with NYHA class IV
- History of alcohol abuse or drug abuse within 6 months prior to Screening Diagnosis at any time of Type 1 diabetes.
- Current or history of recent (≤ 6 months) use of ursodeoxycholic acid.
- Current use of insulin.
- Current use of thiazolidinediones.
- Any history or current concomitant disorder such as haematological, pulmonary, metabolic, endocrine disorders that are severe or life-threatening.
- Use of concomitant medications with a known significant metabolism by CYP2C8 including paclitaxel or repaglinide for the duration of the study.
- History of diabetic ketoacidosis or hyperosmolar non-ketotic coma within the 6 months prior to Screening.
- 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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
MSDC-0602K
Placebo
Arm Description
MSDC-0602K one tablet per day taken orally
Placebo one tablet per day taken orally
Outcomes
Primary Outcome Measures
Change in glycosylated hemoglobin (HbA1c) from baseline to Week 26
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.
Secondary Outcome Measures
Time to first event of death, adjudicated nonfatal MI or USA hospitalization, adjudicated hospital admission for HF, or adjudicated nonfatal ischemic stroke.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03970031
Brief Title
A Study of MSDC-0602K to Assess Glycemic Control and Cardiovascular Outcomes in Patients With Pre-T2D or T2D and NAFLD/NASH
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Not yet recruiting
Study Start Date
June 2022 (Anticipated)
Primary Completion Date
September 2024 (Anticipated)
Study Completion Date
September 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cirius Therapeutics, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a randomized, double-blind study of MSDC-0602K or placebo in subjects with pre-T2D or T2D and evidence of NAFLD/NASH.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type2 Diabetes, NASH - Nonalcoholic Steatohepatitis, Nonalcoholic Steatohepatitis, Non-Alcoholic Fatty Liver Disease
Keywords
Diabetes, NASH, NAFLD
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
1800 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
MSDC-0602K
Arm Type
Active Comparator
Arm Description
MSDC-0602K one tablet per day taken orally
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo one tablet per day taken orally
Intervention Type
Drug
Intervention Name(s)
MSDC-0602K
Intervention Description
MSDC-0602K tablet
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching tablet
Primary Outcome Measure Information:
Title
Change in glycosylated hemoglobin (HbA1c) from baseline to Week 26
Time Frame
26 weeks
Title
Change in the weighted average of standardized AST, CK-18, and HbA1c values (standard deviations) from baseline to Week 26
Description
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.
Time Frame
26 weeks
Secondary Outcome Measure Information:
Title
Time to first event of death, adjudicated nonfatal MI or USA hospitalization, adjudicated hospital admission for HF, or adjudicated nonfatal ischemic stroke.
Time Frame
through study completion, an expected average of 15 months
Title
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.
Description
A liver event consists of ascites (confirmed by paracentesis or abdominal imaging), hepatic encephalopathy (defined clinically), variceal hemorrhage (confirmed by endoscopy), or liver transplant.
Time Frame
through study completion, an expected average of 15 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Written informed consent.
Adult subjects with an age of > 18 years but < 80 years.
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
Diagnosis of NAFLD
AST>27 U/L
HgbA1c >6%
Diagnosis of Pre-T2D or T2D
History of macrovascular cardiovascular disease
Key Exclusion Criteria:
Prior liver transplantation or currently on transplant list.
Other well-documented causes of active chronic liver disease
Current cirrhosis
Pregnant or nursing women
AST or ALT > 5 times the upper limit of normal
Total bilirubin > 1.3 mg/dL unless diagnosis of Gilbert's disease with direct bilirubin within normal reference range
Serum albumin < 3.5 g/dL at Screening
Alkaline phosphatase >2 times the upper limit of normal at Screening
Estimated glomerular filtration rate (eGFR by MDRD) <30 ml/min/1.73 m2 but ≤75 ml/min/1.73 m2
In patients who are not anticoagulated, INR ≥ 1.3 times ULN at Screening or other evidence of impaired coagulation.
Acute vascular events including ACS, stroke or TIA, worsening of peripheral vascular disease or any vascular/cardiac procedure
Limb amputation for reason other than trauma.
HbA1c >10%
Any planned surgery or device implantation after screening
Ejection fraction < 35% or Heart failure with NYHA class IV
History of alcohol abuse or drug abuse within 6 months prior to Screening Diagnosis at any time of Type 1 diabetes.
Current or history of recent (≤ 6 months) use of ursodeoxycholic acid.
Current use of insulin.
Current use of thiazolidinediones.
Any history or current concomitant disorder such as haematological, pulmonary, metabolic, endocrine disorders that are severe or life-threatening.
Use of concomitant medications with a known significant metabolism by CYP2C8 including paclitaxel or repaglinide for the duration of the study.
History of diabetic ketoacidosis or hyperosmolar non-ketotic coma within the 6 months prior to Screening.
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.
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Study of MSDC-0602K to Assess Glycemic Control and Cardiovascular Outcomes in Patients With Pre-T2D or T2D and NAFLD/NASH
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