A Phase 2a, Multicenter, Open-label, Multiple Ascending Dose Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Resmetirom in Pediatric Subjects Ages 6-17 Years With MASH With Fibrosis Stage F1-F3
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 61
- 试验地点
- 2
- 主要终点
- Safety and tolerability of multiple ascending doses of resmetirom
研究概览
简要总结
This study will evaluate the safety, pharmacokinetics (how the body absorbs, distributes, metabolizes, and eliminates the drug), and pharmacodynamics (how the drug affects the body) of resmetirom in children and adolescents with metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis. Participants will receive oral resmetirom once daily for approximately 14 days at one of several dose levels. The information from this study will help determine appropriate dosing and further evaluate the safety and biological effects of resmetirom in pediatric participants with MASH.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female participants 6 to 17 years of age, inclusive.
- •Parent(s) or legal guardian(s) able to provide written informed consent (as required by local regulations), with participant assent obtained as applicable.
- •Diagnose of MASH with fibrosis stage F1-F3 based on a liver biopsy obtained within 24 months before Screening.
- •Hepatic fat fraction ≥8% by magnetic resonance imaging-proton density fat fraction (MRI-PDFF) obtained during the Screening period.
- •Able to swallow study tablets.
- •Females of childbearing potential must have a negative pregnancy test at screening, must not be pregnant or breastfeeding, and must agree to use a highly effective method of contraception during the study and for at least 30 days after the last dose of study drug. Premenarchal participants and those not of childbearing potential are eligible without contraception.
排除标准
- •Previous exposure to resmetirom.
- •Clinically significant liver disease other than MASH or evidence of cirrhosis (F4), decompensated liver disease, or other hepatic conditions that may interfere with study participation or interpretation of results.
- •Clinically significant thyroid disease or use of thyroid replacement therapy, triiodothyronine, thyroxine, or other prohibited thyroid medications.
- •Use of prohibited concomitant medications, including medications known to affect hepatic steatosis or liver function, lipid-lowering therapies, CYP2C8 inhibitors, OATP1B1/OATP1B3/BCRP inhibitors, protease inhibitors, St. John's Wort, or other medications prohibited by the protocol.
- •Use of glucagon-like peptide-1 (GLP-1) receptor agonists unless on a stable dose for at least 24 weeks before screening.
- •Clinically significant alcohol or substance abuse, or regular use of tobacco/nicotine products within 6 months before screening.
- •Active or clinically significant infection, including chronic hepatitis B or hepatitis C infection, HIV infection, or other immunocompromising conditions.
- •History or presence of clinically significant cardiovascular, pulmonary, renal, gastrointestinal, neurologic, hematologic, endocrine, psychiatric, or other medical conditions that, in the opinion of the Investigator, could interfere with study participation or interpretation of study results.
- •History of malignancy within the past 5 years (except adequately treated non-melanoma skin cancer or other protocol-permitted exceptions).
- •History of organ transplantation or known immunocompromised status.
- •Participation in another investigational study within 60 days or 5 half-lives (whichever is longer) before screening, unless permitted by the protocol.
- •Major surgery within 6 weeks before screening.
- •Known hypersensitivity to resmetirom or any excipient.
- •Females who are pregnant or breastfeeding.
- •Any condition that, in the opinion of the Investigator, would compromise participant safety, compliance, or the integrity of the study.
研究组 & 干预措施
Adolescent Dose-Escalation Cohort 1
Adolescents participants 12 to 17 years of age receive the first planned dose level of oral resmetirom once daily for approximately 14 days
干预措施: Resmetirom (Drug)
Adolescent Dose-Escalation Cohort 2
Adolescent participants 12 to 17 years of age receive the second planned dose level of oral resmetirom once daily for approximately 14 days following review of safety and PK data.
干预措施: Resmetirom (Drug)
Child Dose-Escalation Cohort 7
Children participants 6 to 11 years of age receive the second planned dose level of oral resmetirom once daily for approximately 14 days following review of safety and PK data.
干预措施: Resmetirom (Drug)
Child Dose-Escalation Cohort 8
Children participants 6 to 11 years of age receive the third planned dose level of oral resmetirom once daily for approximately 14 days following review of safety and PK data.
干预措施: Resmetirom (Drug)
Adolescent Dose-Escalation Cohort 5
Adolescent participants 12 to 17 years of age receive the fifth planned dose level of oral resmetirom once daily for approximately 14 days following review of safety and PK data.
干预措施: Resmetirom (Drug)
Adolescent Dose-Escalation Cohort 3
Adolescent participants 12 to 17 years of age receive the third planned dose level of oral resmetirom once daily for approximately 14 days following review of safety and PK data.
干预措施: Resmetirom (Drug)
Adolescent Dose-Escalation Cohort 4
Adolescent participants 12 to 17 years of age receive the fourth planned dose level of oral resmetirom once daily for approximately 14 days following review of safety and PK data.
干预措施: Resmetirom (Drug)
Child Dose-Escalation Cohort 6
Children participants 6 to 11 years of age receive the first planned dose level of oral resmetirom once daily for approximately 14 days.
干预措施: Resmetirom (Drug)
Child Dose-Escalation Cohort 9
Children participants 6 to 11 years of age receive the fourth planned dose level of oral resmetirom once daily for approximately 14 days following review of safety and PK data.
干预措施: Resmetirom (Drug)
结局指标
主要结局
Safety and tolerability of multiple ascending doses of resmetirom
时间窗: Baseline through approximately Day 21 (or the protocol-defined safety follow-up period)
Safety and tolerability will be assessed by the incidence and severity of adverse events, serious adverse events, clinical laboratory evaluations, vital signs, 12-lead electrocardiograms, physical examinations, and other protocol-defined safety assessments.
次要结局
- Pharmacokinetic parameters of resmetirom (MGL-3196) and its metabolite (MGL-3623)(Day 1 through Day 14)
- Pharmacodynamic biomarkers associated with resmetirom exposure(Baseline through Day 21)