A Phase 3 Study to Evaluate the Safety and Biomarkers of Resmetirom (MGL-3196) in Non Alcoholic Fatty Liver Disease (NAFLD) Patients (MAESTRO-NAFLD1)

• ClinicalTrials.gov Identifier: NCT04197479
• Recruitment Status: Recruiting
• First Posted: December 13, 2019
• Last Update Posted: December 18, 2019
• Sponsor: Madrigal Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Madrigal Pharmaceuticals, Inc.

Study Description

Brief Summary:

A double-blind placebo controlled randomized Phase 3 study to evaluate the safety and tolerability of once-daily, oral administration of 80 or 100 mg resmetirom versus matching placebo. 100 patients will be enrolled in a 100 mg open-label arm.

Condition or disease	Intervention/treatment	Phase
Non-Alcoholic Fatty Liver Disease	Drug: Placebo; Drug: Resmetirom	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 700 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A 52-Week, Phase 3 Study to Evaluate Safety and Biomarkers of Resmetirom (MGL-3196) in Patients With Non-alcoholic Fatty Liver Disease (NAFLD) (MAESTRO-NAFLD-1)
• Estimated Study Start Date: December 2019
• Estimated Primary Completion Date: December 2021
• Estimated Study Completion Date: December 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Open label: resmetirom; 100 mg daily	Drug: Resmetirom; Tablet; Other Name: MGL-3196
Placebo Comparator: Double blinded: matching placebo; Placebo daily	Drug: Placebo; Matching tablets
Experimental: Double blinded: resmetirom 80 mg; 80 mg daily	Drug: Resmetirom; Tablet; Other Name: MGL-3196
Experimental: Double blinded: resmetirom 100 mg; 100 mg daily	Drug: Resmetirom; Tablet; Other Name: MGL-3196

Outcome Measures

Primary Outcome Measures :

1. The effect of once daily, oral administration of 80 or 100 mg resmetirom versus placebo on the incidence of adverse events. [ Time Frame: 52 weeks ]

Secondary Outcome Measures :

1. The effect of once daily, oral administration of 80 or 100 mg resmetirom versus placebo on the percent change in low density lipoprotein C (LDL-C) from baseline to Week 24 [ Time Frame: 24 weeks ]
2. The effect of once daily, oral administration of 80 or 100 mg resmetirom versus placebo on the percent change in apolipoprotein B (ApoB) from baseline to Week 24 [ Time Frame: 24 weeks ]
3. The effect of once daily, oral administration of 80 or 100 mg resmetirom versus placebo on the percent change in hepatic fat fraction as determined by MRI-PDFF from baseline to Week 16. [ Time Frame: 16 weeks ]
4. The effect of once daily, oral administration of 80 or 100 mg resmetirom versus placebo on the percent change in triglycerides (TGs) from baseline to Week 24 in patients with baseline TG > 150 mg/dL. [ Time Frame: 24 weeks ]
5. The effect of once daily, oral administration of 80 or 100 mg resmetirom versus placebo after 52 weeks on N-terminal type III collagen propeptide (PRO-C3) in patients with baseline PRO-C3 ≥10 ng/mL. [ Time Frame: 52 weeks ]

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Must be willing to participate in the study and provide written informed consent.
• Male and female adults ≥18 years of age.

• Suspected or confirmed diagnosis of NASH or NAFLD (presumed NASH):

  • Fibroscan with kPa ≥5.5 and <8.5; CAP ≥280 dB.m-1 OR
  • MRE >2 and <4.0; MRI‑PDFF ≥8% liver fat consistent with steatosis and fibrosis stage ≥1 and <4. OR

  • Recent liver biopsy (within past 2 years) documenting NASH/NAFLD with steatosis showing one of the following:

    • NAS ≥4, steatosis ≥1, fibrosis stage 0 or 1A/1C with PRO-C3 <14
    • NAS <4, steatosis ≥1, with fibrosis stage ≤3
    • NAS ≥4, steatosis ≥1, fibrosis stage ≤3 without ballooning
• MRI-PDFF fat fraction ≥8% obtained during the Screening Period (baseline MRI-PDFF) or a historic MRI-PDFF ≤8 weeks old at the time of randomization.
• Stable dyslipidemia therapy for ≥30 days prior to randomization.

Exclusion Criteria:

• History of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to Screening.
• Regular use of drugs historically associated with NAFLD.
• History of bariatric surgery or intestinal bypass surgery within the 5 years prior to randomization or planned during the conduct of the study.
• Weight gain or loss ≥5% total body weight within 12 weeks prior to randomization.
• HbA1c >9.0%.
• Glucagon-like peptide 1 [GLP-1] agonist therapy or high dose vitamin E (>400 IU/day) unless stable for 24 weeks prior to biopsy.
• Presence of cirrhosis on liver biopsy defined as stage 4 fibrosis.
• Diagnosis of hepatocellular carcinoma (HCC).
• Model for End-stage Liver Disease (MELD) score ≥12, as determined at Screening, unless due to therapeutic anti coagulation or Gilbert syndrome.
• Hepatic decompensation.
• Chronic liver diseases.
• Has an active autoimmune disease.
• Serum ALT >250 U/L.
• History of biliary diversion.
• Uncontrolled hypertension (either treated or untreated).
• Active, serious medical disease with a likely life expectancy <2 years.
• Participation in an investigational new drug trial in the 60 days or 5 half-lives, whichever is longer, prior to randomization.
• 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.

Contacts and Locations

Contacts

Contact: Edward Chiang; 267-520-0252; info@madrigalpharma.com

Locations

United States, Louisiana

Madrigal Clinical Site 0102; Recruiting

Marrero, Louisiana, United States, 70072

Contact: Madrigal Investigator

United States, Texas

Madrigal Clinical Site 0104; Recruiting

Austin, Texas, United States, 78746

Contact: Madrigal Investigator

Madrigal Clinical Site 0101; Recruiting

San Antonio, Texas, United States, 78229

Contact: Madrigal Investigator

Sponsors and Collaborators

Madrigal Pharmaceuticals, Inc.

Investigators

• Study Director: Rebecca Taub, MD; Madrigal Pharmaceuticals, Inc.

More Information

• Responsible Party: Madrigal Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT04197479
• Other Study ID Numbers: MGL-3196-14
• First Posted: December 13, 2019
• Last Update Posted: December 18, 2019
• Last Verified: December 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Madrigal Pharmaceuticals, Inc.:

NAFLD; NASH; Hyperlipidemia; Resmetirom; Thyroid hormone receptor beta; Hepatic; Fibrosis; NASH resolution; Thyroid hormone receptor agonist; Cardiovascular; Dyslipidemia; Fatty liver disease; Nonalcoholic steatohepatitis

Additional relevant MeSH terms:

Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Digestive System Diseases; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs