Study of MGL-3196 in Patients With Heterozygous Familial Hypercholesterolemia (HeFH)

May 18, 2026 updated by: Madrigal Pharmaceuticals, Inc.

A Phase 2, Multi-Center, Double-Blind, Randomized, Placebo Controlled Study of MGL-3196 in Patients With Heterozygous Familial Hypercholesterolemia

The primary objective of this study is to determine the effect of once-daily oral MGL-3196 on the percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in participants with Heterozygous Familial Hypercholesterolemia (HeFH).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
116

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Aalborg, Denmark
        • Madrigal Research Site
      • Copenhagen, Denmark
        • Madrigal Research Site
      • Esbjerg, Denmark
        • Madrigal Research Site
      • Herlev, Denmark
        • Madrigal Research Site
      • Viborg, Denmark
        • Madrigal Research Site
  • Netherlands
      • Amsterdam, Netherlands
        • Madrigal Research Site
      • Apeldoorn, Netherlands
        • Madrigal Research Site
      • Goes, Netherlands
        • Madrigal Research Site
      • Hoorn, Netherlands
        • Madrigal Research Site
      • Nijmegen, Netherlands
        • Madrigal Research Site
      • Zwijndrecht, Netherlands
        • Madrigal Research Site
  • Norway
      • Oslo, Norway
        • Madrigal Research Site - 1
      • Oslo, Norway
        • Madrigal Research Site - 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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) test who are not breastfeeding, do not plan to become pregnant during the study, and agree to use effective birth control per locally agreed requirements; 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 either be 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 a diagnosis of HeFH by genetic testing or by having met the diagnostic criteria for definite familial hypercholesterolemia outlined by the Simon Broome Register Group or World Health Organization/Dutch Lipid Network (score >8);
  • Must have had a fasting LDL-C (low density lipoprotein cholesterol) ≥2.6 mmol/L (100 mg/dL); and
  • Must be on a stable or maximally tolerated dose (≥4 weeks prior to screening) of an approved statin (rosuvastatin ≤40 mg daily, atorvastatin ≤80 mg daily), with or without ezetimibe. Patients intolerant to statins were allowed.

Exclusion Criteria:

  • Homozygous familial hypercholesterolemia
  • LDL or plasma apheresis within 2 months prior to randomization;
  • New York Heart Association class III or IV heart failure, or known left ventricular ejection fraction <30%;
  • Uncontrolled cardiac arrhythmia, including confirmed QT interval corrected using Fridericia's formula >450 msec for males and >470 msec for females at the screening electrocardiogram assessment;
  • Myocardial infarction, unstable angina, percutaneous coronary intervention, coronary artery bypass graft, or stroke within 3 months prior to randomization;
  • Type 1 diabetes, or newly diagnosed or uncontrolled type 2 diabetes (hemoglobin A1c >8%);
  • History of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to screening; Note: Significant alcohol consumption is defined as average of >20 g/day in female participants and >30 g/day in male participants;
  • Hyperthyroidism;
  • Thyroid replacement therapy;
  • Hypothyroidism;
  • Evidence of chronic liver disease;
  • Hepatitis B, as defined by the presence of hepatitis B surface antigen;
  • Hepatitis C, as defined by the presence of hepatitis C virus (HCV) antibody (anti-HCV) and HCV ribonucleic acid (RNA). Participants with positive anti-HCV who test negative for HCV RNA at screening will be allowed to participate in the study;
  • Serum alanine aminotransferase >1.5 x upper limit of normal (ULN) (one repeat allowed);
  • Estimated glomerular filtration rate <60 mL/min;
  • Creatine kinase >3 x ULN (one repeat allowed);
  • History of biliary diversion;
  • Positive for human immunodeficiency virus infection;
  • History of malignant hypertension;
  • Systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg at screening or randomization and confirmed at an unscheduled visit;
  • Triglycerides >5.7 mmol/L (500 mg/dL) at screening and confirmed by repeat assessment;
  • Active, serious medical disease with likely life expectancy <2 years;
  • Active substance abuse, including inhaled or injection drugs within the year prior to screening;
  • Participation in an investigational new drug trial within 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, or compromise the well-being of the participants.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo
Matching Placebo
Drug: Placebo
Oral
Experimental: MGL-3196
Study Drug
Drug: MGL-3196 (resmetirom)
Oral

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Mean Percent Change in LDL-C From Baseline To Week 12
Time Frame: Baseline up to Week 12
LDL-C was determined by ultracentrifugation or direct measure. Least-squares (LS) mean was provided for the comparison of MGL-3196 versus placebo and it used a linear model with percent change from baseline as the dependent variable and treatment as a factor.
Baseline up to Week 12

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Mean Change From Baseline to Week 12 of Free Thyroxine (T4)
Time Frame: Baseline up to Week 12
T4 was assessed at each study visit.
Baseline up to Week 12
Mean Change From Baseline to Week 12 of Free Triiodothyronine (T3)
Time Frame: Baseline up to Week 12
Free T3 was assessed at each study visit.
Baseline up to Week 12
Mean Change From Baseline to Week 12 of Thyrotropin (TSH)
Time Frame: Baseline up to Week 12
TSH was assessed at each study visit.
Baseline up to Week 12
Mean Change From Baseline to Week 12 of Thyroxine Binding Globulin (TBG)
Time Frame: Baseline up to Week 12
TBG was assessed at all study visits except the Screening Visit.
Baseline up to Week 12
Mean Change From Baseline to Week 12 of Reverse Triiodothyronine (T3)
Time Frame: Baseline up to Week 12
Reverse T3 was assessed at each study visit.
Baseline up to Week 12
Mean Percent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 12
Time Frame: Baseline up to Week 12
Non-HDL-C were determined by ultracentrifugation. LS mean was provided for the comparison of MGL-3196 versus placebo and it used a linear model with percent change from baseline as the dependent variable and treatment as a factor
Baseline up to Week 12
Mean Percent Change In Triglycerides From Baseline To Week 12
Time Frame: Baseline up to Week 12
Triglycerides were determined by ultracentrifugation. LS mean was provided for the comparison of MGL-3196 versus placebo and it used a linear model with percent change from baseline as the dependent variable and treatment as a factor.
Baseline up to Week 12
Mean Percent Change In Lipoprotein(a) (Lp[a]) From Baseline To Week 12
Time Frame: Baseline up to Week 12
Lp(a) was determined by ultracentrifugation. LS mean was provided for the comparison of MGL-3196 versus placebo and it used a linear model with percent change from baseline as the dependent variable and treatment as a factor.
Baseline up to Week 12
Mean Percent Change in Apolipoprotein CIII From Baseline to Week 12
Time Frame: Baseline up to Week 12
Apolipoprotein CIII was determined by ultracentrifugation. LS mean was provided for the comparison of MGL-3196 versus placebo and it used a linear model with percent change from baseline as the dependent variable and treatment as a factor.
Baseline up to Week 12
Mean Percent Change In Apolipoprotein B (ApoB) From Baseline To Week 12
Time Frame: Baseline up to Week 12
ApoB was determined by ultracentrifugation. LS mean was provided for the comparison of MGL-3196 versus placebo and it used a linear model with percent change from baseline as the dependent variable and treatment as a factor.
Baseline up to Week 12
Mean Percent Change in Apolipoprotein B/Apolipoprotein A1 (ApoB/ApoA1) Ratio From Baseline to Week 12
Time Frame: Baseline up to Week 12
The ApoB/ApoA1 ratio was determined by ultracentrifugation. LS mean was provided for the comparison of MGL-3196 versus placebo and it used a linear model with percent change from baseline as the dependent variable and treatment as a factor.
Baseline up to Week 12
Mean Percent Change In Cholesterol/HDL-C Ratio From Baseline to Week 12
Time Frame: Baseline up to Week 12
The Cholesterol/HDL-C Ratio was determined by ultracentrifugation. LS mean was provided for the comparison of MGL-3196 versus placebo and it used a linear model with percent change from baseline as the dependent variable and treatment as a factor.
Baseline up to Week 12
Absolute Change in LDL-C From Baseline to Week 12
Time Frame: Baseline up to Week 12
LDL-C was determined by ultracentrifugation or direct measure . Least-squares (LS) mean was provided for the comparison of MGL-3196 versus placebo and it used a linear model with percent change from baseline as the dependent variable and treatment as a factor.
Baseline up to Week 12
Percent Change From Baseline in LDL-C at Week 2 and Week 4 in Patients in the 100 mg and the 60 mg Groups
Time Frame: Baseline to Week 2 and Week 4
LDL-C was determined by ultracentrifugation or direct measure. Least-squares (LS) mean was provided for the comparison of MGL-3196 versus placebo and it used a linear model with percent change from baseline as the dependent variable and treatment as a factor.
Baseline to Week 2 and Week 4
Percent Change in LDL-C From Baseline to Week 12 by Systemic Exposure Category
Time Frame: Baseline to Week 12
The effect on percent change in LDL-C from baseline to Week 12 was determined by patient exposure category (higher/lower). Patients taking MGL-3196 were categorized into lower and higher exposure groups. Patients in the higher exposure group must either have had estimated Week 2 AUC ≥5,000 mg∙h/L, or if Week 2 AUC <5,000 mg∙h/L but Week 4 pre-dose concentration >1.5 ng/mL (if on 60 mg MGL-3196). All other patients were in the lower exposure group.
Baseline to Week 12
Mean Change in Lipid Particle Concentration From Baseline To Week 12: Total LDL Particles
Time Frame: Baseline up to Week 12
The effect of once-daily oral dosing of MGL-3196 versus placebo for 12 weeks in terms of change from baseline was assessed for LDL Particles.
Baseline up to Week 12
Mean Change in Lipid Particle Concentration From Baseline To Week 12: Small LDL Particles
Time Frame: Baseline up to Week 12
The effect of once-daily oral dosing of MGL-3196 versus placebo for 12 weeks in terms of change from baseline was assessed for Small LDL Particles.
Baseline up to Week 12
Mean Change in Lipid Particle Concentration From Baseline To Week 12: Intermediate LDL Particles
Time Frame: Baseline up to Week 12
The effect of once-daily oral dosing of MGL-3196 versus placebo for 12 weeks in terms of change from baseline was assessed for Intermediate LDL Particles.
Baseline up to Week 12
Mean Change in Lipid Particle Concentration From Baseline To Week 12: Large LDL Particles
Time Frame: Baseline up to Week 12
The effect of once-daily oral dosing of MGL-3196 versus placebo for 12 weeks in terms of change from baseline was assessed for Large LDL Particles.
Baseline up to Week 12
Mean Change in Lipid Particle Concentration From Baseline To Week 12:Total Very Low-Density Lipoprotein (VLDL) and Chylomicron Particles
Time Frame: Baseline up to Week 12
The effect of once-daily oral dosing of MGL-3196 versus placebo for 12 weeks in terms of change from baseline was assessed for VLDL and Chylomicron Particles.
Baseline up to Week 12
Mean Change in Lipid Particle Concentration From Baseline To Week 12: Total HDL Particles
Time Frame: Baseline up to Week 12
The effect of once-daily oral dosing of MGL-3196 versus placebo for 12 weeks in terms of change from baseline was assessed for Total HDL Particles.
Baseline up to Week 12
Mean Change in Lipid Particle Concentration From Baseline To Week 12: LDL Particle Size
Time Frame: Baseline up to Week 12
The effect of once-daily oral dosing of MGL-3196 versus placebo for 12 weeks in terms of change from baseline was assessed for LDL Particle size.
Baseline up to Week 12
Mean Change in Lipid Particle Concentration From Baseline To Week 12: VLDL Particle Size
Time Frame: Baseline up to Week 12
The effect of once-daily oral dosing of MGL-3196 versus placebo for 12 weeks in terms of change from baseline was assessed for VLDL Particle Size.
Baseline up to Week 12
Mean Change in Lipid Particle Concentration From Baseline To Week 12: HDL Particle Size
Time Frame: Baseline up to Week 12
The effect of once-daily oral dosing of MGL-3196 versus placebo for 12 weeks in terms of change from baseline was assessed for HDL Particle Size.
Baseline up to Week 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Madrigal Pharmaceuticals, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Rebecca Taub, MD, Madrigal Pharmaceuticals, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 23, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 15, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 15, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 30, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 30, 2017

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 31, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 4, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 18, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MGL-3196-06
  • 2016-002315-17 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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