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History of Changes for Study: NCT03900429
A Phase 3 Study to Evaluate the Efficacy and Safety of MGL-3196 (Resmetirom) in Patients With NASH and Fibrosis
Latest version (submitted July 6, 2021) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 March 30, 2019 None (earliest Version on record)
2 May 8, 2019 Study Status and Study Identification
3 July 15, 2019 Study Status and Outcome Measures
4 December 9, 2019 Outcome Measures, Study Status, Contacts/Locations and Eligibility
5 October 19, 2020 Contacts/Locations and Study Status
6 December 8, 2020 Study Status and Contacts/Locations
7 March 1, 2021 Study Status and Contacts/Locations
8 July 6, 2021 Study Status and Contacts/Locations
Comparison Format:

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Study NCT03900429
Submitted Date:  March 30, 2019 (v1)

Open or close this module Study Identification
Unique Protocol ID: MGL-3196-11
Brief Title: A Phase 3 Study to Evaluate the Efficacy and Safety of MGL-3196 (Resmetirom) in Patients With NASH and Fibrosis
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
Secondary IDs:
Open or close this module Study Status
Record Verification: March 2019
Overall Status: Recruiting
Study Start: March 28, 2019
Primary Completion: June 30, 2021 [Anticipated]
Study Completion: March 31, 2024 [Anticipated]
First Submitted: March 26, 2019
First Submitted that
Met QC Criteria:
March 30, 2019
First Posted: April 3, 2019 [Actual]
Last Update Submitted that
Met QC Criteria:
March 30, 2019
Last Update Posted: April 3, 2019 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Madrigal Pharmaceuticals, Inc.
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
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
Detailed Description:
Open or close this module Conditions
Conditions: NASH - Nonalcoholic Steatohepatitis
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 3
Interventional Study Model: Parallel Assignment
Number of Arms: 3
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation: Randomized
Enrollment: 2000 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Placebo Comparator: Matching Placebo
Placebo Daily
Drug: Placebo
Matching Tablets
Active Comparator: 80 mg MGL-3196
80 mg daily
Drug: MGL-3196
Tablet
Other Names:
  • Resmetirom
Active Comparator: 100 mg MGL-3196
100 mg daily
Drug: MGL-3196
Tablet
Other Names:
  • Resmetirom
Open or close this module Outcome Measures
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.
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
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.
Open or close this module Contacts/Locations
Central Contact Person: Kimberly Dorney, RN, MSN
Telephone: 267-520-0252
Email: info@madrigalpharma.com
Study Officials: Rebecca Taub
Study Director
Madrigal Pharmaceuticals, Inc.
Locations: United States, Texas
Pinnacle Clinical Research
[Recruiting]
San Antonio, Texas, United States, 78229
Contact:Contact: Gail Hinkson
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Links:
Available IPD/Information:

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