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A Phase 3 Study to Evaluate the Efficacy and Safety of MGL-3196 (Resmetirom) in Patients With NASH and Fibrosis (MAESTRO-NASH)

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ClinicalTrials.gov Identifier: NCT03900429
Recruitment Status : Recruiting
First Posted : April 3, 2019
Last Update Posted : July 17, 2019
Sponsor:
Information provided by (Responsible Party):
Madrigal Pharmaceuticals, Inc.

Brief Summary:
A double-blind placebo controlled randomized Phase 3 study to determine if 80 or 100 mg of MGL-3196 as compared with placebo resolves NASH on liver biopsy and prevents progression to cirrhosis and/or advanced liver disease

Condition or disease Intervention/treatment Phase
NASH - Nonalcoholic Steatohepatitis Drug: MGL-3196 Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 2000 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Multinational, Double-Blind, Randomized, Placebo-Controlled Study of MGL-3196 (Resmetirom) in Patients With Non-Alcoholic Steatohepatitis (NASH) and Fibrosis to Resolve NASH and Reduce Progression to Cirrhosis and/or Hepatic Decompensation
Actual Study Start Date : March 28, 2019
Estimated Primary Completion Date : June 30, 2021
Estimated Study Completion Date : March 31, 2024


Arm Intervention/treatment
Placebo Comparator: Matching Placebo
Placebo Daily
Drug: Placebo
Matching Tablets

Active Comparator: 80 mg MGL-3196
80 mg daily
Drug: MGL-3196
Tablet
Other Name: Resmetirom

Active Comparator: 100 mg MGL-3196
100 mg daily
Drug: MGL-3196
Tablet
Other Name: Resmetirom




Primary Outcome Measures :
  1. To evaluate the effect of MGL-3196 80 mg or 100 mg compared to placebo to achieve NASH resolution on liver histology in non-cirrhotic NASH patients with stage 2 or 3 fibrosis [ Time Frame: Measurements at Baseline and 52 weeks ]
    Assessment will be in the first 900 patients, at least 450 F3, and be based on the proportion of MGL-3196 80 mg or 100 mg treated patients relative to placebo achieving NASH resolution (NASH Activity Score (NAS), ballooning =0; lobular inflammation =0,1) with at least a 2 point reduction in NAS and no worsening of fibrosis.

  2. Composite long-term outcome composed of all-cause mortality, cirrhosis, and liver-related clinical outcomes [ Time Frame: Time frame to acrue a prespecified number of adjudicated events, up to 54 months ]
    To evaluate the effect of MGL-3196 80 mg or 100 mg compared to placebo on composite long-term outcome measured by the number of patients with the onset of any of the adjudicated events, composed of cirrhosis, all-cause mortality, liver-related clinical outcomes.


Secondary Outcome Measures :
  1. To determine the effect of once-daily, oral administration of MGL-3196 80 or 100 mg versus matching placebo on the percent change from Baseline at 24 weeks in low-density lipoprotein cholesterol (LDL-C) [ Time Frame: Baseline and 24 weeks ]
  2. To evaluate the effect of MGL-3196 80 mg or 100 mg compared to placebo to achieve improvement in fibrosis on liver histology in non-cirrhotic NASH patients with stage 2 or 3 fibrosis [ Time Frame: Baseline and 52 weeks ]
    Assessment will be in the first 900 patients, at least 450 F3, and be based on the proportion of MGL-3196 80 mg or 100 mg treated patients relative to placebo achieving at least a 1-point improvement in fibrosis (NASH Clinical Research Network system) by liver biopsy with no worsening of NAS.


Other Outcome Measures:
  1. To evaluate the effect of MGL-3196 80 mg or 100 mg compared to placebo to achieve NASH resolution on liver histology in non-cirrhotic NASH patients with stage 1 fibrosis [ Time Frame: Baseline and 52 weeks ]
    Assessment will be in stage 1 fibrosis patients and be based on the proportion of MGL-3196 80 mg or 100 mg treated patients relative to placebo achieving NASH resolution (NASH Activity Score (NAS), ballooning =0; lobular inflammation =0,1) with at least a 2 point reduction in NAS and no worsening of fibrosis.



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

Inclusion Criteria:

  1. Must be willing to participate in the study and provide written informed consent.
  2. Male and female adults ≥ 18 years of age.
  3. Suspected or confirmed diagnosis of NASH

    1. Metabolic risk factors and AST > 20 U/L
    2. Criteria consistent with liver fibrosis: fibrosis biomarkers or fibroscan or historical liver biopsy with NASH andstage 2 or 3 fibrosis

      • Biochemical test for fibrosis
      • Fibroscan
      • Historical liver biopsy with NASH and Stage 2 or 3 Fibrosis
  4. MRI-PDFF with increased fat fraction
  5. Biopsy-proven NASH (Baseline liver biopsy) based on a liver biopsy obtained within 24 weeks before anticipated date of randomization (if the biopsy is deemed acceptable for interpretation by the central reader) with fibrosis stage 1A, 1B, 2, or 3 on liver biopsy and NAS of ≥ 4 with a score of at least 1 in each of the following NAS components:

    1. Steatosis (scored 0 to 3)
    2. Ballooning degeneration (scored 0 to 2)
    3. Lobular inflammation (scored 0 to 3)

Exclusion Criteria:

  1. History of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to Screening.
  2. Regular use of drugs historically associated with NAFLD
  3. History of bariatric surgery or intestinal bypass surgery within the 5 years prior to randomization or planned during the conduct of the study.
  4. Recent significant weight gain or loss
  5. HbA1c ≥ 9.0%.
  6. Glucagon-like peptide 1 [GLP-1] agonist , high dose Vitamin E (> 400 IU/day) or pioglitazone therapy unless stable dose for 24 weeks prior to biopsy.
  7. Presence of cirrhosis on liver biopsy defined as stage 4 fibrosis.
  8. Diagnosis of hepatocellular carcinoma (HCC).
  9. MELD score ≥12, as determined at Screening, unless due to therapeutic anti coagulation.
  10. Hepatic decompensation
  11. Chronic liver diseases other than NASH
  12. Active autoimmune disease
  13. Serum ALT > 250 U/L.
  14. Active, serious medical disease with a likely life expectancy < 2 years.
  15. Participation in an investigational new drug trial in the 60 days or 5 half-lives, whichever is longer.
  16. 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.

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): NCT03900429


Contacts
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Contact: Kimberly Dorney, RN, MSN 267-520-0252 info@madrigalpharma.com

Locations
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United States, Texas
Pinnacle Clinical Research Recruiting
San Antonio, Texas, United States, 78229
Contact: Gail Hinkson         
Sponsors and Collaborators
Madrigal Pharmaceuticals, Inc.
Investigators
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Study Director: Rebecca Taub Madrigal Pharmaceuticals, Inc.

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Responsible Party: Madrigal Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03900429     History of Changes
Other Study ID Numbers: MGL-3196-11
First Posted: April 3, 2019    Key Record Dates
Last Update Posted: July 17, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Fatty Liver
Non-alcoholic Fatty Liver Disease
Liver Diseases
Digestive System Diseases