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

Primary Purpose

Heterozygous Familial Hypercholesterolemia

Status
Completed
Phase
Phase 2
Locations
Denmark
Study Type
Interventional
Intervention
MGL-3196
Placebo
Sponsored by
Madrigal Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heterozygous Familial Hypercholesterolemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Must be willing to participate in the study and provide written informed consent;
  • Male and female adults ≥18 years of age;
  • Female patients 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 (ie, condoms, diaphragm, non-hormonal intrauterine device [IUD], or sexual abstinence [only if this is in line with the patient'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 (eg, condoms); OR female patients of non-child bearing potential (ie, surgically [bilateral oophorectomy, hysterectomy, or tubal ligation] or naturally sterile [>12 consecutive months without menses]); male patients 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 patients 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 WHO/Dutch Lipid Network (score >8);
  • Must have a fasting LDL-C ≥ 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 ≤ 20 mg daily, atorvastatin ≤ 80 mg daily), with or without ezetimibe.

Exclusion Criteria:

  • Homozygous familial hypercholesterolemia
  • Low-density lipoprotein (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 (QTcF) >450 msec for males and >470 msec for females at the screening electrocardiogram (ECG) 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 [HbA1c] >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 patients and >30 g/day in male patients;
  • Thyroid replacement therapy;
  • 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). Patients with positive anti-HCV who test negative for HCV RNA at screening will be allowed to participate in the study;
  • Serum alanine aminotransferase (ALT) >1.5 × ULN (one repeat allowed);
  • Estimated glomerular filtration rate <60 mL/min;
  • Creatine kinase >3 × 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 patient.

Sites / Locations

  • Madrigal Research Site
  • Madrigal Research Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

MGL-3196

Placebo

Arm Description

Study Drug

Matching Placebo

Outcomes

Primary Outcome Measures

Mean percent change from baseline in low-density lipoprotein cholesterol (LDL-C)

Secondary Outcome Measures

Safety and tolerability of MGL-3196 based on Adverse Events and Changes in Laboratory Values
Mean percent change from baseline on selected lipid parameters
Non-high-density lipoprotein cholesterol (non-HDL-C),Apolipoprotein B (ApoB), Total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio, Triglycerides,Lipoprotein(a), Apolipoprotein A1 (ApoA1)/ApoB ratio, and Lipoprotein particle assessment

Full Information

First Posted
January 30, 2017
Last Updated
January 23, 2018
Sponsor
Madrigal Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03038022
Brief Title
Study of MGL-3196 in Patients With Heterozygous Familial Hypercholesterolemia (HeFH)
Official Title
A Phase 2, Multi-Center, Double-Blind, Randomized, Placebo Controlled Study of MGL-3196 in Patients With Heterozygous Familial Hypercholesterolemia
Study Type
Interventional

2. Study Status

Record Verification Date
January 2018
Overall Recruitment Status
Completed
Study Start Date
February 9, 2017 (Actual)
Primary Completion Date
December 18, 2017 (Actual)
Study Completion Date
January 15, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Madrigal Pharmaceuticals, Inc.

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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 patients with Heterozygous Familial Hypercholesterolemia (HeFH).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heterozygous Familial Hypercholesterolemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
116 (Actual)

8. Arms, Groups, and Interventions

Arm Title
MGL-3196
Arm Type
Experimental
Arm Description
Study Drug
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matching Placebo
Intervention Type
Drug
Intervention Name(s)
MGL-3196
Intervention Description
Oral
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Oral
Primary Outcome Measure Information:
Title
Mean percent change from baseline in low-density lipoprotein cholesterol (LDL-C)
Time Frame
12 Weeks
Secondary Outcome Measure Information:
Title
Safety and tolerability of MGL-3196 based on Adverse Events and Changes in Laboratory Values
Time Frame
12 Weeks
Title
Mean percent change from baseline on selected lipid parameters
Description
Non-high-density lipoprotein cholesterol (non-HDL-C),Apolipoprotein B (ApoB), Total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio, Triglycerides,Lipoprotein(a), Apolipoprotein A1 (ApoA1)/ApoB ratio, and Lipoprotein particle assessment
Time Frame
12 Weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Must be willing to participate in the study and provide written informed consent; Male and female adults ≥18 years of age; Female patients 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 (ie, condoms, diaphragm, non-hormonal intrauterine device [IUD], or sexual abstinence [only if this is in line with the patient'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 (eg, condoms); OR female patients of non-child bearing potential (ie, surgically [bilateral oophorectomy, hysterectomy, or tubal ligation] or naturally sterile [>12 consecutive months without menses]); male patients 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 patients 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 WHO/Dutch Lipid Network (score >8); Must have a fasting LDL-C ≥ 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 ≤ 20 mg daily, atorvastatin ≤ 80 mg daily), with or without ezetimibe. Exclusion Criteria: Homozygous familial hypercholesterolemia Low-density lipoprotein (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 (QTcF) >450 msec for males and >470 msec for females at the screening electrocardiogram (ECG) 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 [HbA1c] >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 patients and >30 g/day in male patients; Thyroid replacement therapy; 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). Patients with positive anti-HCV who test negative for HCV RNA at screening will be allowed to participate in the study; Serum alanine aminotransferase (ALT) >1.5 × ULN (one repeat allowed); Estimated glomerular filtration rate <60 mL/min; Creatine kinase >3 × 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 patient.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rebecca Taub, MD
Organizational Affiliation
Madrigal Pharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Madrigal Research Site
City
Aalborg
Country
Denmark
Facility Name
Madrigal Research Site
City
Viborg
Country
Denmark

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35331419
Citation
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.
Results Reference
derived

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

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