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Trial record 1 of 1 for:    emminence
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A Study to Evaluate the Safety, Tolerability & Efficacy of MSDC 0602K in Patients With NASH (EMMINENCE)

This study is currently recruiting participants.
Verified June 2017 by Cirius Therapeutics, Inc.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02784444
First Posted: May 27, 2016
Last Update Posted: June 22, 2017
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.
Collaborator:
Chiltern International Inc.
Information provided by (Responsible Party):
Cirius Therapeutics, Inc.
  Purpose
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. The primary efficacy endpoint, hepatic histological improvement in NAS will be assessed at 12 months. Visits to the clinic will be at baseline, 1, 2, 3, 6, 9, and 12 months, with one 2- week follow-up visit.

Condition Intervention Phase
Non-alcoholic Fatty Liver Disease Non-alcoholic Steatohepatitis NASH - Nonalcoholic Steatohepatitis Drug: MSDC-0602K Drug: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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™)

Resource links provided by NLM:


Further study details as provided by Cirius Therapeutics, Inc.:

Primary Outcome Measures:
  • Hepatic histological improvement in NASH defined as a decrease in the NAS with no concurrent worsening of fibrosis at 12 months [ Time Frame: 12 months (360 days) ]
    Decrease in the NAS by at least 2 points with no concurrent worsening of fibrosis using NASH CRN fibrosis staging system


Secondary Outcome Measures:
  • Number of participants with treatment-related adverse events [ Time Frame: 12 months (360 days) ]
  • Proportion of patients that achieve resolution of NASH by hepatic histology [ Time Frame: 12 months (360 days) ]
    Resolution of NASH is defined as a ballooning score of 0 and an inflammation score of 0-1 without worsening of fibrosis.

  • Proportion of patients that achieve an improvement in liver fibrosis [ Time Frame: 12 months (360 days) ]
    Reduction from baseline of at least one point by NASH CRN scoring

  • Mean changes in the NAFLD activity score and each one of its components (steatosis, inflammation and ballooning) [ Time Frame: 12 months (360 days) ]
  • Mean changes from baseline in fibrosis score (NASH CRN scoring) at 12 months. [ Time Frame: 12 months (360 days) ]

Estimated Enrollment: 200
Study Start Date: July 2016
Estimated Study Completion Date: October 2018
Estimated Primary Completion Date: October 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: MSDC-0602K Dose 1 capsules
MSDC-0602K Dose 1 capsules taken once daily for 360 days
Drug: MSDC-0602K
MSDC-0602K capsules
Active Comparator: MSDC-0602K Dose 2 capsules
MSDC-0602K Dose 2 capsules taken once daily for 360 days
Drug: MSDC-0602K
MSDC-0602K capsules
Active Comparator: MSDC-0602K Dose 3 capsules
MSDC-0602K Dose 3 capsules taken once daily for 360 days
Drug: MSDC-0602K
MSDC-0602K capsules
Placebo Comparator: Placebo capsules
Matching Placebo capsules taken once daily for 360 days
Drug: Placebo
Placebo capsules

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. Subjects will be stratified by presence of T2DM (Yes/No), use of Vitamin E ≥ 400 IU (Yes/No) and fibrosis score (1 or ≥ 2) to ensure equal representation across all groups. The primary efficacy endpoint, as well as some secondary endpoints, will be assessed at 12 months. Visits to the clinic will be at baseline, 1, 2, 3, 6, 9, and 12 months, with one 2- week follow-up visit.

Approximately 200 subjects will be randomized with the intent to have 180 subjects complete the 12 month assessment at approximately 35 sites in the US.

Each patient will self-administer one study drug capsule orally with water at least 30 minutes before breakfast each day.

This study will be comprised of a maximum 30-day Screening period, a treatment period of 360 days and a 14-day follow-up period. The total duration of the study for each patient will be approximately 404 days, including follow-up.

Safety will be assessed by periodic measurement of vital signs, 12 lead electrocardiogram (ECG), physical examinations and questions regarding potential adverse events (AEs). Fasting blood samples for clinical chemistries and hematology will be collected at each study visit (Screening and Study Visits 1-8). Samples for urinalysis will be collected at Screening and most Study Visits. Blood samples for PK analysis will be taken at most Study Visits throughout the trial.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 Stage 1 to 3.
  • Male and female subjects with NASH and a fibrosis score of F1 to F3 (NASH CRN scoring) with interpretable liver biopsy within 6 months prior to start of study. If no usable liver biopsy is available within 6 months prior to start of study, subjects must agree to have a liver biopsy performed at Screening for those eligible subjects who meet all other entry criteria. All eligible subjects must agree to have one liver biopsy at the end of study treatment (one year).
  • If the subjects have type 2 diabetes, they must be under stable and reasonable control. Male and female subjects with reasonably controlled type 2 diabetes mellitus (DM) are defined as under physician's care for diabetes with glycosylated hemoglobin [HbA1c] ≤ 9.5%. If the subjects are taking permitted anti-diabetic therapies, they must be on stable doses of the following antidiabetics for a period of at least 3 months prior to the diagnostic liver biopsy: metformin, GLP-1 agonists, SGLT2 inhibitors, sulfonylureas, or DPP4 inhibitors. Refer to Section 4.3 for additional clarification about the use of antidiabetics.
  • 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 the diagnostic liver biopsy.
  • 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.
  • Willing and able to make a Screening visit to the clinic and eight visits over a 12.5 month period.

Exclusion Criteria:

  • Known history of HIV.
  • Prior liver transplantation.
  • Other well-documented causes of active chronic liver disease, including, but not restricted to: history of positive hepatitis B surface antigen (HBsAg) or HCV RNA, suspicion of drug-induced liver disease, alcoholic liver disease and auto-immune hepatitis, Wilson's disease hemochromatosis, primary biliary cirrhosis, primary sclerosing cholangitis, genetic hemochromatosis, known or suspected HCC, history of planned liver transplant or current MELD score >12. Subjects need to be viremia free for 2 years.
  • History of cirrhosis and/or hepatic decompensation including ascites, hepatic encephalopathy or variceal bleeding. Platelet count < 100,000/µL of blood.
  • AST and ALT > 160 U/L.
  • Bilirubin > 1.8 mg/dL and/or serum albumin < 2.5 gms/dL.
  • Impaired coagulation or PT/INR ≥ 1.5 times ULN.
  • History of alcohol abuse or drug abuse within 6 months of Screening.
  • Inability to safely obtain a liver biopsy.
  • Type 1 diabetes mellitus.
  • Use of ursodeoxycholic acid.
  • Use of any diabetes medications other than metformin, GLP-1 agonists, SGLT2 inhibitors, sulfonylureas, or DPP4 inhibitors three months prior to the baseline diagnostic liver biopsy or during the study unless as specified in the protocol. Use of insulin or PPARγ agonists (pioglitazone or rosiglitazone) are not allowed. Refer to Section 4.3 for additional clarification about the use of antidiabetics.
  • Use of concomitant medications with a known significant metabolism by CYP2C8 or CPY2C9 including: paclitaxel, phenytoin, warfarin, celecoxib, tolbutamide, and replaglinide.
  • History of diabetic ketoacidosis or hyperosmolar non-ketotic coma.
  • History of heart failure (including CHF) or previous cardiovascular event (myocardial infarct, by-pass surgery, or PTCA) within the past 6 months prior to Screening.
  • Serum creatinine >2 mg/dL.
  • Current or recurrent disease that may affect the action, absorption or disposition of the study treatment, or clinical or laboratory assessments.
  • Current or history of severe or unstable disorder (medical or psychiatric) requiring treatment that may make the patient unlikely to complete the study.
  • Blood pressure greater than 160/100 mmHg. Patients with elevated BP (but <160/100 mmHg) with or without current treatment will be allowed at the discretion of the Investigator and primary care physician. Individuals with hypertension must have been stabilized to the current treatment regimen for at least 6 weeks prior to Screening.
  • Known or suspected intolerance or hypersensitivity to the study drugs, closely related compounds or any of their stated ingredients.
  • Have participated in an investigational study or received an investigational drug within 30 days or 5 half-lives (whichever is longer) prior to study drug administration.
  • Blood donation of 1 pint or more within 56 days of Screening.
  • Plasmapheresis or plasma donation within 30 days of Screening.
  • Single 12-lead ECG demonstrating a QTcB >450 msec at Screening. A single repeat ECG may be done at the Investigator's discretion.
  • Any surgical or medical condition which may significantly alter the absorption of any drug substance including, but not limited to, any of the following: history of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, bowel resection, gastric bypass, gastric stapling, or gastric banding, currently active inflammatory bowel syndrome.
  • Evidence of clinically relevant pathology that could interfere with the study results or put the patient's safety at risk.
  • Malignancy, including leukemia and lymphoma (not including basal cell skin cancer) not treated within the last 5 years.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02784444


Contacts
Contact: Janet Combs 423-990-0361 Janet.Combs@chiltern.com

  Show 42 Study Locations
Sponsors and Collaborators
Cirius Therapeutics, Inc.
Chiltern International Inc.
Investigators
Study Director: Howard Dittrich, MD Cirius Therapeutics, Inc.
  More Information

Responsible Party: Cirius Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02784444     History of Changes
Other Study ID Numbers: MSDC-0602K-C009NASH
First Submitted: May 18, 2016
First Posted: May 27, 2016
Last Update Posted: June 22, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Cirius Therapeutics, Inc.:
NASH

Additional relevant MeSH terms:
Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Digestive System Diseases


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