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

NCT03038022 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: MGL-3196-062016-002315-17
• Study Type: interventional
• Target: 116
• Locations: 3 countries
• Sites: 13

Brief Summary

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).

Conditions

Heterozygous Familial Hypercholesterolemia

Outcome Measures

Primary Outcomes (1)

• Mean Percent Change in LDL-C From Baseline 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 Outcomes (24)

• Mean Change From Baseline to Week 12 of Free Thyroxine (T4)

  Baseline up to Week 12

• Mean Change From Baseline to Week 12 of Free Triiodothyronine (T3)

  Baseline up to Week 12

• Mean Change From Baseline to Week 12 of Thyrotropin (TSH)

  Baseline up to Week 12

• Mean Change From Baseline to Week 12 of Thyroxine Binding Globulin (TBG)

  Baseline up to Week 12

• Mean Change From Baseline to Week 12 of Reverse Triiodothyronine (T3)

  Baseline up to Week 12

Study Arms (2)

MGL-3196

EXPERIMENTAL

Study Drug

Drug: MGL-3196 (resmetirom)

Placebo

PLACEBO COMPARATOR

Matching Placebo

Drug: Placebo

Interventions

MGL-3196 (resmetirom) DRUG

Oral

MGL-3196

Placebo DRUG

Oral

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) 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Madrigal Pharmaceuticals, Inc.: lead

Study Sites (13)

Madrigal Research Site

Aalborg, Denmark

Location

Madrigal Research Site

Copenhagen, Denmark

Location

Madrigal Research Site

Esbjerg, Denmark

Location

Madrigal Research Site

Herlev, Denmark

Location

Madrigal Research Site

Viborg, Denmark

Location

Madrigal Research Site

Amsterdam, Netherlands

Location

Madrigal Research Site

Apeldoorn, Netherlands

Location

Madrigal Research Site

Goes, Netherlands

Location

Madrigal Research Site

Hoorn, Netherlands

Location

Madrigal Research Site

Nijmegen, Netherlands

Location

Madrigal Research Site

Zwijndrecht, Netherlands

Location

Madrigal Research Site - 1

Oslo, Norway

Location

Madrigal Research Site - 2

Oslo, Norway

Location

Related Publications (1)

• Hovingh GK, Klausen IC, Heggen E, McCarty K, Zhou R, Isaac BF, Taub R, Langslet G, Kastelein JJP. Resmetirom (MGL-3196) in Patients With Heterozygous Familial Hypercholesterolemia. J Am Coll Cardiol. 2022 Mar 29;79(12):1220-1222. doi: 10.1016/j.jacc.2022.01.023. No abstract available.

  PMID: 35331419 DERIVED

MeSH Terms

Interventions

resmetirom

Results Point of Contact

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

thare@madrigalpharma.com

267-268-7800

Study Officials

• Rebecca Taub, MD

  Madrigal Pharmaceuticals, Inc.

  STUDY DIRECTOR

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: January 30, 2017
• First Posted: January 31, 2017
• Study Start: February 23, 2017
• Primary Completion: January 15, 2018
• Study Completion: January 15, 2018
• Last Updated: December 23, 2025
• Results First Posted: December 23, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

NL (6); NO (2); DK (5)