Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Phase 2 Study of MGL-3196 in Patients With Non-Alcoholic Steatohepatitis (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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02912260
Recruitment Status : Unknown
Verified December 2017 by Madrigal Pharmaceuticals, Inc..
Recruitment status was:  Active, not recruiting
First Posted : September 23, 2016
Last Update Posted : December 19, 2017
Sponsor:
Information provided by (Responsible Party):
Madrigal Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE September 19, 2016
First Posted Date  ICMJE September 23, 2016
Last Update Posted Date December 19, 2017
Study Start Date  ICMJE September 2016
Actual Primary Completion Date October 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 20, 2016)
Change from baseline in hepatic fat fraction assessed by MRI-PDFF [ Time Frame: 12 weeks ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 20, 2016)
  • Two-point reduction in Non-alcoholic fatty liver disease NASH CRN (NAFLD) activity score (NAS) [ Time Frame: 36 weeks ]
  • Resolution of Non-alcoholic steatohepatitis (NASH) (ballooning = 0; inflammation = 0 to 1) as determined by the NASH CRN NAS score [ Time Frame: 36 weeks ]
  • Improvement in fibrosis by at least 1 stage with no worsening of steatohepatitis [ Time Frame: 36 weeks ]
  • Change from baseline in hepatic fat fraction [ Time Frame: 36 weeks ]
  • Safety and tolerability of MGL-3196 based on Adverse Events and Changes in Laboratory Values [ Time Frame: 12 and 36 weeks ]
  • Effect on high-sensitivity C-reactive protein (hsCRP) [ Time Frame: 12 and 36 weeks ]
  • Effect on serum alanine aminotransferase (ALT) [ Time Frame: 12 and 36 weeks ]
  • Effect on aspartate aminotransferase (AST) [ Time Frame: 12 and 36 weeks ]
  • Effect on lipid parameters [ Time Frame: 12 and 36 weeks ]
    Determine the effect on lipid parameters including low-density lipoprotein cholesterol (LDL-C), non- LDL-C, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, total cholesterol, triglycerides, apolipoprotein B (ApoB), and lipoprotein(a) (Lp[a]) particles.
  • Effect on NASH and fibrosis biomarkers [ Time Frame: 12 and 36 weeks ]
    Determine the effect on NASH and fibrosis biomarkers including cytokeratin-18 (CK-18), fibrosis-4 (FIB-4), and enhanced liver function (ELF) test.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase 2 Study of MGL-3196 in Patients With Non-Alcoholic Steatohepatitis (NASH)
Official Title  ICMJE A Phase 2, Multi-Center, Double-Blind, Randomized, Placebo-controlled Study of MGL-3196 in Patients With Non-alcoholic Steatohepatitis
Brief Summary The primary objective of this study is to determine the effect of once-daily oral MGL-3196 on the percent change in hepatic fat fraction from baseline in patients with biopsy-proven Non-alcoholic Steatohepatitis (NASH).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Non-alcoholic Steatohepatitis
Intervention  ICMJE
  • Drug: MGL-3196
  • Drug: Placebo
Study Arms  ICMJE
  • Experimental: MGL-3196
    Study Drug
    Intervention: Drug: MGL-3196
  • Placebo Comparator: Placebo
    Matching Placebo
    Intervention: Drug: Placebo
Publications * Harrison SA, Bashir MR, Guy CD, Zhou R, Moylan CA, Frias JP, Alkhouri N, Bansal MB, Baum S, Neuschwander-Tetri BA, Taub R, Moussa SE. Resmetirom (MGL-3196) for the treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet. 2019 Nov 30;394(10213):2012-2024. doi: 10.1016/S0140-6736(19)32517-6. Epub 2019 Nov 11.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Actual Enrollment  ICMJE
 (submitted: August 1, 2017)
125
Original Estimated Enrollment  ICMJE
 (submitted: September 20, 2016)
117
Estimated Study Completion Date  ICMJE April 2018
Actual Primary Completion Date October 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria. Patients who meet all of the following criteria will be eligible to participate in the study:

  • Must be willing to participate in the study and provide written informed consent;
  • Male and female adults ≥18 years of age with a BMI <45 kg/m^2;
  • Female patients of child bearing potential with negative serum pregnancy (beta human chorionic gonadotropin) tests who are not breastfeeding, do not plan to become pregnant during the study, and agree to use effective birth control (ie, condoms, diaphragm, non hormonal intrauterine device [IUD], or sexual abstinence [only if this is in line with the patient's current lifestyle]) throughout the study and for at least 1 month after study completion; hormonal contraception (estrogens stable ≥3 months) and hormonal IUDs are permitted if used with a secondary birth control measure (eg, condoms); OR female patients of non-child bearing potential (ie, surgically [bilateral oophorectomy, hysterectomy, or tubal ligation] or naturally sterile [>12 consecutive months without menses]); Male patients who have sexual intercourse with a female partner of child bearing potential from the first dose of study drug until 1 month after study completion must be either surgically sterile (confirmed by documented azoospermia >90 days after the procedure) OR agree to use a condom with spermicide. All male patients must agree not to donate sperm from the first dose of study drug until 1 month after study completion;
  • Must have confirmation of ≥10% liver fat content on PDFF-MRI;
  • Biopsy-proven NASH. Must have had prior liver biopsy within 180 days of randomization with fibrosis stage 1 to 3 and a NAS of ≥4 with at least a score of 1 in each of the following NAS components:

    • Steatosis (scored 0 to 3),
    • Ballooning degeneration (scored 0 to 2), and
    • Lobular inflammation (scored 0 to 3);
  • Must have documented historical (3 weeks to 6 months prior to the study entry) ALT and AST levels consistent with the screening ALT and AST values.

Exclusion Criteria. Patients who meet any of the following criteria will be excluded from participation in the study:

Note: Unless otherwise specified, repeat testing may be performed in consultation with the Medical Monitor.

  • History of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to screening;
  • Weight gain or loss >5% in the 6 months prior to randomization or >10% in the 12 months prior to screening;
  • Hyperthyroidism;
  • Patients on thyroid replacement therapy;
  • Prior or planned (during the study period) bariatric surgery (eg, gastroplasty, roux-en-Y gastric bypass);
  • Type 1 diabetes;
  • Uncontrolled Type 2 diabetes defined as Hemoglobin A1c ≥ 9.5% at screening (patients with HbA1c ≥ 9.5% may be rescreened);
  • Use of obeticholic acid, ursodeoxycholic acid (Ursodiol® and Urso®), high dose vitamin E (>400 IU/day) unless on stable dose of vitamin E >400 IU/day for at least 6 months at the time of liver biopsy, or pioglitazone within 90 days prior to enrollment or since screening biopsy, whichever is longer;
  • Presence of cirrhosis on liver biopsy (stage 4 fibrosis);
  • Platelet count < 140,000/mm^3;
  • Clinical evidence of hepatic decompensation;
  • Evidence of other forms of chronic liver disease;
  • Active, serious medical disease with likely life expectancy <2 years;
  • Participation in an investigational new drug trial in the 30 days prior to randomization; or
  • Any other condition which, in the opinion of the Investigator, would impede compliance, hinder completion of the study, compromise the well-being of the patient, or interfere with the study outcomes.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02912260
Other Study ID Numbers  ICMJE MGL-3196-05
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Madrigal Pharmaceuticals, Inc.
Study Sponsor  ICMJE Madrigal Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Madrigal Pharmaceuticals, Inc.
Verification Date December 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP