Phase 2 Study of MGL-3196 in Patients With Non-Alcoholic Steatohepatitis (NASH)

NCT02912260 | Completed Phase 2 Results DMC

• 1 other identifier: MGL-3196-05
• Study Type: interventional
• Target: 125
• Locations: 1 country
• Sites: 26

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 participants with biopsy-proven Non-alcoholic Steatohepatitis (NASH).

Conditions

Non-alcoholic Steatohepatitis

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline To Week 12 In Hepatic Fat Fraction Assessed By Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF)

  The primary endpoint was relative change in MRI-PDFF assessed hepatic fat fraction compared with placebo at Week 12 in participants who had both a baseline and Week 12 MRI-PDFF. Least squares (LS) mean was provided for the statistical comparison of MGL-3196 versus placebo.

  Week 12

Secondary Outcomes (41)

• Percentage Of Participants With Adverse Events (AEs)

  Week 12 and Week 36

• Percent Change From Baseline To Week 36 In Hepatic Fat Fraction Assessed By MRI-PDFF

  Week 36

• Change From Baseline To Week 12 In Absolute Hepatic Fat Fraction Assessed By MRI-PDFF

  Week 12

• Change From Baseline To Week 36 In Absolute Hepatic Fat Fraction Assessed By MRI-PDFF

  Week 36

• Percentage Of Participants With At Least 30% Relative Fat Reduction at Week 12

  Week 12

Study Arms (2)

MGL-3196

EXPERIMENTAL

Study Drug

Drug: MGL-3196

Placebo

PLACEBO COMPARATOR

Matching Placebo

Drug: Placebo

Interventions

MGL-3196 DRUG

MGL-3196

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must be willing to participate in the study and provide written informed consent;
• Male and female adults ≥18 years of age;
• Female participants 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 (that is, condoms, diaphragm, nonhormonal intrauterine device \[IUD\], or sexual abstinence \[only if this is in line with the participant's current lifestyle\]) 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 (for example, condoms); or female participants of non-child bearing potential (that is, surgically \[bilateral oophorectomy, hysterectomy, or tubal ligation\] or naturally sterile \[\>12 consecutive months without menses\]); Male participants 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 participants 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 magnetic resonance imaging proton density fat fraction;
• Biopsy-proven NASH. Must have had prior liver biopsy within 180 days of randomization with fibrosis stage 1 to 3 and a non-alcoholic fatty liver disease activity score (NAS) of ≥4 with a score of 1 or more 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) alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels consistent with the screening ALT and AST values.

You may not qualify if:

• 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;
• Hyperthyroidism;
• Participants on thyroid replacement therapy (with exceptions);
• Prior or planned (during the study period) bariatric surgery (for example, gastroplasty, roux-en-Y gastric bypass);
• Type 1 diabetes;
• Uncontrolled Type 2 diabetes defined as Hemoglobin A1c (HbA1c) ≥ 9.5% at screening (participants 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 participant, or interfere with the study outcomes.

Sponsors & Collaborators

• Madrigal Pharmaceuticals, Inc.: lead

Study Sites (26)

Madrigal Research Site

Dothan, Alabama, United States

Location

Madrigal Research Site

Tucson, Arizona, United States

Location

Madrigal Research Site

Coronado, California, United States

Location

Madrigal Research Site

Los Angeles, California, 90057, United States

Location

Madrigal Research Site

Rialto, California, United States

Location

Madrigal Research Site

San Diego, California, United States

Location

Madrigal Research Site

Ventura, California, United States

Location

Madrigal Research Site

Englewood, Colorado, United States

Location

Madrigal Research Site

Boca Raton, Florida, United States

Location

Madrigal Research Site

Lakewood Rch, Florida, United States

Location

Madrigal Research Site

Lauderdale Lakes, Florida, United States

Location

Madrigal Research Site

Miami, Florida, United States

Location

Madrigal Research Site

New Port Richey, Florida, United States

Location

Madrigal Research Site

Kansas City, Kansas, United States

Location

Madrigal Research Site

Monroe, Louisiana, United States

Location

Madrigal Research Site

Baltimore, Maryland, United States

Location

Madrigal Research Site

Jackson, Mississippi, 39202, United States

Location

Madrigal Research Site

St Louis, Missouri, United States

Location

Madrigal Research Site

Albuquerque, New Mexico, United States

Location

Madrigal Research Site

New York, New York, United States

Location

Madrigal Research Site

Durham, North Carolina, United States

Location

Madrigal Research Site

Rapid City, South Dakota, United States

Location

Madrigal Research Site

Live Oak, Texas, 78233, United States

Location

Madrigal Research Site

San Antonio, Texas, United States

Location

Madrigal Research Site

Charlottesville, Virginia, United States

Location

Madrigal Research Site

Seattle, Washington, United States

Location

Related Publications (4)

• Harrison SA, Ratziu V, Anstee QM, Noureddin M, Sanyal AJ, Schattenberg JM, Bedossa P, Bashir MR, Schneider D, Taub R, Bansal M, Kowdley KV, Younossi ZM, Loomba R. Design of the phase 3 MAESTRO clinical program to evaluate resmetirom for the treatment of nonalcoholic steatohepatitis. Aliment Pharmacol Ther. 2024 Jan;59(1):51-63. doi: 10.1111/apt.17734. Epub 2023 Oct 2.

  PMID: 37786277 DERIVED

• Younossi ZM, Stepanova M, Taub RA, Barbone JM, Harrison SA. Hepatic Fat Reduction Due to Resmetirom in Patients With Nonalcoholic Steatohepatitis Is Associated With Improvement of Quality of Life. Clin Gastroenterol Hepatol. 2022 Jun;20(6):1354-1361.e7. doi: 10.1016/j.cgh.2021.07.039. Epub 2021 Jul 27.

  PMID: 34329774 DERIVED

• Harrison SA, Bashir M, Moussa SE, McCarty K, Pablo Frias J, Taub R, Alkhouri N. Effects of Resmetirom on Noninvasive Endpoints in a 36-Week Phase 2 Active Treatment Extension Study in Patients With NASH. Hepatol Commun. 2021 Jan 4;5(4):573-588. doi: 10.1002/hep4.1657. eCollection 2021 Apr.

  PMID: 33860116 DERIVED

• 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.

  PMID: 31727409 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

resmetirom

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: Thomas Hare
• Organization: Madrigal Pharmaceuticals, Inc.

thare@madrigalpharma.com

267-268-7800

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2016
• First Posted: September 23, 2016
• Study Start: October 18, 2016
• Primary Completion: October 25, 2017
• Study Completion: November 23, 2021
• Last Updated: December 23, 2025
• Results First Posted: December 23, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (26)