NCT03038022已完成2 期
A Phase 2, Multi-Center, Double-Blind, Randomized, Placebo Controlled Study of MGL-3196 in Patients With Heterozygous Familial Hypercholesterolemia
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 116
- 试验地点
- 13
- 主要终点
- Mean Percent Change in LDL-C From Baseline To Week 12
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
MGL-3196
Experimental
Study Drug
干预措施: MGL-3196 (resmetirom) (Drug)
Placebo
Placebo Comparator
Matching Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Mean Percent Change in LDL-C From Baseline To Week 12
时间窗: 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.
次要结局
- 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)
- Mean Percent Change in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 12(Baseline up to Week 12)
- Mean Percent Change In Triglycerides From Baseline To Week 12(Baseline up to Week 12)
- Mean Percent Change In Lipoprotein(a) (Lp[a]) From Baseline To Week 12(Baseline up to Week 12)
- Mean Percent Change in Apolipoprotein CIII From Baseline to Week 12(Baseline up to Week 12)
- Mean Percent Change In Apolipoprotein B (ApoB) From Baseline To Week 12(Baseline up to Week 12)
- Mean Percent Change in Apolipoprotein B/Apolipoprotein A1 (ApoB/ApoA1) Ratio From Baseline to Week 12(Baseline up to Week 12)
- Mean Percent Change In Cholesterol/HDL-C Ratio From Baseline to Week 12(Baseline up to Week 12)
- Absolute Change in LDL-C From Baseline to Week 12(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(Baseline to Week 2 and Week 4)
- Percent Change in LDL-C From Baseline to Week 12 by Systemic Exposure Category(Baseline to Week 12)
- Mean Change in Lipid Particle Concentration From Baseline To Week 12: Total LDL Particles(Baseline up to Week 12)
- Mean Change in Lipid Particle Concentration From Baseline To Week 12: Small LDL Particles(Baseline up to Week 12)
- Mean Change in Lipid Particle Concentration From Baseline To Week 12: Intermediate LDL Particles(Baseline up to Week 12)
- Mean Change in Lipid Particle Concentration From Baseline To Week 12: 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(Baseline up to Week 12)
- Mean Change in Lipid Particle Concentration From Baseline To Week 12: Total HDL Particles(Baseline up to Week 12)
- Mean Change in Lipid Particle Concentration From Baseline To Week 12: LDL Particle Size(Baseline up to Week 12)
- Mean Change in Lipid Particle Concentration From Baseline To Week 12: VLDL Particle Size(Baseline up to Week 12)
- Mean Change in Lipid Particle Concentration From Baseline To Week 12: HDL Particle Size(Baseline up to Week 12)
研究者
研究点 (13)
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