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Non-alcoholic SteatohepatitisPhase 2NCT02912260

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

A Phase 2 study testing MGL-3196 in people with Non-alcoholic Steatohepatitis, run by Madrigal Pharmaceuticals, Inc. at 26 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-alcoholic Steatohepatitis
What is being tested?
MGL-3196
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
125 participants
Where
26 sitesUnited States
Study dates
18 Oct 2016to 23 Nov 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Inclusion Criteria. Participants 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;
  • 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.

Exclusion Criteria. Participants 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;
  • 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.

Trial locations and contacts

26 sites in 1 country.

26 sites in 1 country

United States26 sites

  • Madrigal Research Site

    Albuquerque, New Mexico

  • Madrigal Research Site

    Baltimore, Maryland

  • Madrigal Research Site

    Boca Raton, Florida

  • Madrigal Research Site

    Charlottesville, Virginia

  • Madrigal Research Site

    Coronado, California

  • Madrigal Research Site

    Dothan, Alabama

  • Madrigal Research Site

    Durham, North Carolina

  • Madrigal Research Site

    Englewood, Colorado

  • Madrigal Research Site

    Jackson, Mississippi, 39202

  • Madrigal Research Site

    Kansas City, Kansas

  • Madrigal Research Site

    Lakewood Rch, Florida

  • Madrigal Research Site

    Lauderdale Lakes, Florida

  • Madrigal Research Site

    Live Oak, Texas, 78233

  • Madrigal Research Site

    Los Angeles, California, 90057

  • Madrigal Research Site

    Miami, Florida

  • Madrigal Research Site

    Monroe, Louisiana

  • Madrigal Research Site

    New Port Richey, Florida

  • Madrigal Research Site

    New York, New York

  • Madrigal Research Site

    Rapid City, South Dakota

  • Madrigal Research Site

    Rialto, California

  • Madrigal Research Site

    San Antonio, Texas

  • Madrigal Research Site

    San Diego, California

  • Madrigal Research Site

    Seattle, Washington

  • Madrigal Research Site

    St Louis, Missouri

  • Madrigal Research Site

    Tucson, Arizona

  • Madrigal Research Site

    Ventura, California

Other trials in United States

About this study

Official title: A Phase 2, Multi-Center, Double-Blind, Randomized, Placebo-controlled Study of MGL-3196 in Patients With Non-alcoholic Steatohepatitis

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).

Being tested
MGL-3196, Placebo
Medical subject headings
Non-alcoholic Fatty Liver Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MGL-3196Drug

  • PlaceboDrug

Study groups in NCT02912260
Study groupRoleWhat they receive
MGL-3196ExperimentalStudy Drug
Receives: Drug: MGL-3196
PlaceboPlacebo comparatorMatching Placebo
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Week 12

Secondary outcomes (41)

  1. Percentage Of Participants With Adverse Events (AEs)

    An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with the treatment. A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

    Measured: Week 12 and Week 36

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

    The endpoint was relative change assessed hepatic fat fraction compared with placebo at Week 36. LS mean was provided for the statistical comparison of MGL-3196 versus placebo.

    Measured: Week 36

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

    The endpoint was change in MRI-PDFF assessed absolute hepatic fat fraction compared with placebo at Week 12. LS mean was provided for the comparison of MGL-3196 versus placebo.

    Measured: Week 12

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

    The endpoint was change in assessed absolute hepatic fat fraction compared with placebo at Week 36. LS mean was provided for the comparison of MGL-3196 versus placebo.

    Measured: Week 36

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

    The endpoint presented the percentage of participants achieving a relative fat reduction of ≥30% at Week 12.

    Measured: Week 12

  6. Percentage Of Participants With At Least 30% Relative Fat Reduction At Week 36

    The endpoint presented the percentage of participants achieving a relative fat reduction of ≥30% at Week 36.

    Measured: Week 36

  7. Percentage Of Participants Achieving A 1-Point Reduction In Non-alcoholic Fatty Liver Disease Activity Score (NAS) At Week 36

    The NAS is a histologic scale for non-alcoholic steatohepatitis (NASH) activity, which combines into a single score steatosis (Grade 0 to 3), ballooning (Grade 0 to 2), and lobular inflammation (Grade 0 to 3). The endpoint presented the percentage of participants with a 1-point or greater reduction in NAS.

    Measured: Week 36

  8. Percentage Of Participants Achieving A 2-Point Reduction In NAS At Week 36

    The NAS is a histologic scale for NASH activity, which combines into a single score steatosis (Grade 0 to 3), ballooning (Grade 0 to 2), and lobular inflammation (Grade 0 to 3). The endpoint presented the percentage of participants with a 2-point or greater reduction in NAS.

    Measured: Week 36

  9. Percentage Of Participants Achieving A 2-Point Reduction In NAS And Either A ≥1-Point Reduction In Lobular Inflammation Or Hepatocellular Ballooning At Week 36

    The NAS is a histologic scale for NASH activity, which combines into a single score steatosis (Grade 0 to 3), ballooning (Grade 0 to 2), and lobular inflammation (Grade 0 to 3). The endpoint presented the percentage of participants with a 2-point or greater reduction in NAS and a 1-point or greater reduction in lobular inflammation or hepatocellular ballooning.

    Measured: Week 36

  10. Percentage Of Participants Achieving A 2-Point Reduction In NAS Without Fibrosis Worsening At Week 36

    The NAS is a histologic scale for NASH activity, which combines into a single score steatosis (Grade 0 to 3), ballooning (Grade 0 to 2), and lobular inflammation (Grade 0 to 3). Fibrosis stage (0 to 3) was also included in the assessment. The endpoint presented the percentage of participants with a 2-point or greater reduction in NAS without worsening fibrosis.

    Measured: Week 36

  11. Percentage Of Participants With A Reduction In Hepatocellular Steatosis At Week 36

    The NAS is a histologic scale for NASH activity, which combines into a single score steatosis (Grade 0 to 3), ballooning (Grade 0 to 2), and lobular inflammation (Grade 0 to 3). The endpoint presented the percentage of participants with a reduction in hepatocellular steatosis.

    Measured: Week 36

  12. Percentage Of Participants With A Reduction In Lobular Inflammation At Week 36

    The NAS is a histologic scale for NASH activity, which combines into a single score steatosis (Grade 0 to 3), ballooning (Grade 0 to 2), and lobular inflammation (Grade 0 to 3). The endpoint presented the percentage of participants with a reduction in lobular inflammation.

    Measured: Week 36

  13. Percentage Of Participants With A Reduction In Hepatocellular Ballooning At Week 36

    The NAS is a histologic scale for NASH activity, which combines into a single score steatosis (Grade 0 to 3), ballooning (Grade 0 to 2), and lobular inflammation (Grade 0 to 3). The endpoint presented the percentage of participants with a reduction in hepatocellular ballooning.

    Measured: Week 36

  14. Percentage Of Participants Achieving NASH Resolution With At Least 2-Point Reduction In NAS At Week 36

    The endpoint presented the percentage of participants achieving NASH resolution with a 2-point reduction at Week 36.

    Measured: Week 36

  15. Percent Change From Baseline To Week 12 In High-sensitivity C-reactive Protein (hsCRP)

    hsCRP was used as a non-invasive inflammation marker for this study. Blood samples were collected to determine the effect of MGL-3196 on hsCRP.

    Measured: Week 12

  16. Percent Change From Baseline To Week 36 In hsCRP

    hsCRP was used as a non-invasive inflammation marker for this study. Blood samples were collected to determine the effect of MGL-3196 on hsCRP.

    Measured: Week 36

  17. Change From Baseline To Week 12 In Serum Alanine Aminotransferase (ALT)

    Blood samples were collected to determine the effect of MGL-3196 on serum ALT.

    Measured: Week 12

  18. Change From Baseline To Week 36 In ALT

    Blood samples were collected to determine the effect of MGL-3196 on serum ALT.

    Measured: Week 36

  19. Change From Baseline To Week 12 In Serum Aspartate Aminotransferase (AST)

    Blood samples were collected to determine the effect of MGL-3196 on serum AST.

    Measured: Week 12

  20. Change From Baseline To Week 36 In AST

    Blood samples were collected to determine the effect of MGL-3196 on serum AST.

    Measured: Week 36

  21. Percent Change From Baseline To Week 12 In Lipid Parameters

    Blood samples were collected to determine the effect of MGL-3196 on lipid parameters including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, total cholesterol (TC), triglycerides (TG), apolipoprotein B (ApoB), and Apolipoprotein CIII (ApoCIII).

    Measured: Week 12

  22. Percent Change From Baseline To Week 36 In Lipid Parameters

    Blood samples were collected to determine the effect of MGL-3196 on lipid parameters including LDL-C, HDL-C, non-HDL-C, TC, TG, ApoB, and ApoCIII.

    Measured: Week 36

  23. Percent Change From Baseline To Week 12 In Lipid Parameter Lipoprotein(a) (Lp[a])

    Blood samples were collected to determine the effect of MGL-3196 on lipid parameter Lp(a).

    Measured: Week 12

  24. Percent Change From Baseline To Week 36 In Lipid Parameter Lp[a]

    Blood samples were collected to determine the effect of MGL-3196 on lipid parameter Lp(a).

    Measured: Week 36

  25. Change From Baseline To Week 12 And Week 36 In Cytokeratin-18 (CK-18)

    Serum CK-18 fragments, detected using the M30 antibody, is a non-invasive biomarker for NASH that may reflect hepatocyte apoptosis.

    Measured: Week 12 and Week 36

  26. Change From Baseline To Week 12 And Week 36 In Enhanced Liver Fibrosis (ELF) Test

    The ELF Test is a non-invasive blood test that provides a simple, unitless numeric score that is used as a marker of collagen formation and fibrogenic activity and can be used to assess the risk of progression to cirrhosis. Scores below 9.8 indicate low risk of disease progression, and scores above 11.29 indicate high risk. The ELF score is derived from values of three serum biomarkers: hyaluronic acid (HA), procollagen III N-terminal peptide (PIIINP), and tissue inhibitor of metalloproteinase-1 (TIMP-1). The formula is 2.278 + 0.851 × ln(HA) + 0.751 × ln(PIIINP) + 0.394 × ln(TIMP-1); there are no minimum or maximum values.

    Measured: Week 12 and Week 36

  27. Change From Baseline To Week 12 And Week 36 In Fibrosis-4 (Fib-4) Score

    The Fib-4 score is a scoring system used to estimate the amount of scarring in the liver. It is based on common clinical parameters (age, AST, ALT, and platelets) and has been shown to have the best diagnostic accuracy for advanced fibrosis when compared with other noninvasive clinical scores. Scores are categorized into low (<1.30), indeterminate (1.30-2.67), or high (>2.67) risk of fibrosis. The formula for Fib-4 is: (Age [yr] x AST [U/L]) / ((PLT [109/L]) x (ALT [U/L])½); there are no minimum or maximum values

    Measured: Week 12 and Week 36

  28. Change From Baseline of Thyrotropin at Week 12

    Thyrotropin (TSH) was assessed at each study visit.

    Measured: Baseline up to Week 12

  29. Change From Baseline of Total Thyroxine at Week 12

    Total thyroxine (FT4) was assessed at each study visit.

    Measured: Baseline up to Week 12

  30. Change From Baseline of Free Thyroxine at Week 12

    Free thyroxine (FT4) was assessed at each study visit.

    Measured: Baseline up to Week 12

  31. Change From Baseline of Total Triiodothyronine at Week 12

    Total Triiodothyronine (T3) was assessed at each study visit.

    Measured: Baseline up to Week 12

  32. Change From Baseline of Free Triiodothyronine at Week 12

    Free triiodothyronine (T3) was assessed at each study visit.

    Measured: Baseline up to Week 12

  33. Change From Baseline of Thyroxine Binding Globulin at Week 12

    Thyroxine Binding Globulin was assessed at each study visit.

    Measured: Baseline up to Week 12

  34. Change From Baseline of Reverse Triiodothyronine Globulin at Week 12

    Reverse Triiodothyronine (T3) was assessed at each study visit.

    Measured: Baseline up to Week 12

  35. Change From Baseline of Thyrotropin at Week 36

    Tyrotropin (TSH) was assessed at each study visit.

    Measured: Baseline up to Week 36

  36. Change From Baseline of Total Thyroxine at Week 36

    Total thyroxine (FT4), thyrotropin (TSH) was assessed at each study visit.

    Measured: Baseline up to Week 36

  37. Change From Baseline of Free Thyroxine Week 36

    Total free thyroxine (FT4) was assessed at each study visit.

    Measured: Baseline up to Week 36

  38. Change From Baseline of Total Triiodothyronine at Week 36

    Total triiodothyronine (T3) was assessed at each study visit.

    Measured: Baseline up to Week 36

  39. Change From Baseline of Free Triiodothyronine at Week 36

    Free triiodothyronine (T3) was assessed at each study visit.

    Measured: Baseline up to Week 36

  40. Change From Baseline of Thyroxine-Binding Globulin at Week 36

    Thyroxine-binding globulin (TBG) was assessed at each study visit.

    Measured: Baseline up to Week 36

  41. Change From Baseline of Reverse Triiodothyronine at Week 36

    Reverse triiodothyronine (T3) was assessed at each study visit.

    Measured: Baseline up to Week 36

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Sep 2016 (estimated)
  2. Study start18 Oct 2016
  3. Primary completion25 Oct 2017
  4. Study completion23 Nov 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
125 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02912260
Sponsor's protocol ID
MGL-3196-05
Status last verified
Sep 2025
First submitted
19 Sep 2016
Last updated
23 Dec 2025
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • 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.

    PubMed 37786277

  • 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.

    PubMed 34329774

  • 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.

    PubMed 33860116

  • 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.

    PubMed 31727409

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing MGL-3196 in people with Non-alcoholic Steatohepatitis, run by Madrigal Pharmaceuticals, Inc. at 26 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent Change From Baseline To Week 12 In Hepatic Fat Fraction Assessed By Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) (time frame: Week 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02912260, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Dec 2025.

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