A 52-Week, Phase 3, Open-Label Extension Study, With a Double-blind Lead-in, to Evaluate Safety and Biomarkers of Resmetirom (MGL-3196) in Patients With Non-alcoholic Fatty Liver Disease (NAFLD), MAESTRO-NAFLD-Open-Label-Extension (MAESTRO-NAFLD-OLE)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 810
- 试验地点
- 146
- 主要终点
- The effect of once daily, oral administration of resmetirom on the incidence of adverse events.
研究概览
简要总结
A 52-Week, Multi-center, Open-label, Active Treatment Extension Study to Evaluate Safety and Tolerability of Once Daily, Oral Administration of Resmetirom (MGL-3196)
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
- Triple (Participant, Care Provider, Investigator)
盲法说明
Select patients will be randomized in 1:1 manner to a double-blind, 12-week lead-in treatment period. Only investigators, patients, and the Sponsor will be blinded to treatment assignment during the double-blind treatment period.
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
- •For patients who completed MAESTRO-NAFLD-1, completed the Week 52 visit, and completed the Week 56 visit within 90 days of the Extension Day 1 visit, and are willing to participate in MAESTRO-NAFLD-OLE and provide written informed consent.
- •For patients who screen failed MAESTRO-NASH, must provide written informed consent for MAESTRO-NAFLD-OLE and must have screened and met all eligibility requirements for MAESTRO-NASH within 90 days of the Extension Day 1 visit for MAESTRO-NAFLD-OLE and have a liver biopsy that is ineligible for MAESTRO-NASH within 6 months of the Extension Day 1 visit. Eligible liver biopsy for MAESTRO-NAFLD-OLE must have one of the following results:
- •NAS = 3, steatosis 1, ballooning 1, inflammation 1, OR NAS = 3, ballooning 0, with F1B, F2 or F3
- •NAS ≥ 4, at least 1 in all NAS components, F1A or F1C, PRO-C3 ≤ 14 (NASH, but ineligible for MAESTRO-NASH)
- •Compensated NASH cirrhosis based on biopsy at screening of MAESTRO-NASH and baseline of MAESTRO-NAFLD-OLE, including Child Pugh-A (score 5-6), MELD <12, albumin ≥3.2, and bilirubin <2
- •For patients who screen failed from MAESTRO-NASH OUTCOMES and de novo patients, must have documented CP-A/B (score <8) NASH cirrhosis (including minimal decompensation) and MELD <15 unless MELD >=15 based on non-cirrhotic parameters. MAESTRO-NASH OUTCOMES screen failures must have screened and met all eligibility requirements for MAESTRO-NASH OUTCOMES within 90 days of the Extension Day 1 visit for MAESTRO-NAFLD-OLE .
排除标准
- •A history of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to Extension Day
- •Diagnosis of hepatocellular carcinoma or other carcinomas that may prevent participation in the Extension study.
- •Chronic liver diseases
- •Has an active autoimmune disease
- •Any other condition which, in the opinion of the Investigator, would impede compliance, hinder completion of the study, compromise the well-being of the patient, or interfere with the study outcomes.
研究组 & 干预措施
Open-label
For patients assigned to open-label treatment and who completed Week 52 and 56 of MAESTRO-NAFLD-1, open-label resmetirom at same dose as MGL-3196-14 for an additional 52 weeks. NASH cirrhosis patients may receive open-label resmetirom for up to an additional 66 months (ie, 52 weeks in MGL-3196-14 and up to 66 months in MGL-3196-18).
干预措施: Resmetirom (Drug)
Open-Label 80 mg
For patients with NASH cirrhosis who were screen failures from MGL-3196-11, open-label resmetirom 80 mg for up to 66 months.
干预措施: Resmetirom (Drug)
Double-blind 100 mg Daily
For patients assigned to double-blind treatment and who completed Week 52 and 56 of MAESTRO-NAFLD-1, double-blind resmetirom 100 mg for first 12 weeks followed by open-label resmetirom 100 mg for weeks 12-52
干预措施: Resmetirom (Drug)
Double-blind 80 mg Daily
For patients assigned to double-blind treatment and who completed Week 52 and 56 of MAESTRO-NAFLD-1, double-blind resmetirom 80 mg for first 12 weeks followed by open-label resmetirom 100 mg for weeks 12-52
干预措施: Resmetirom (Drug)
Open Label 100 mg
For patients without NASH cirrhosis who were screen failures from MGL-3196-11, open-label resmetirom 100 mg for 52 weeks
干预措施: Resmetirom (Drug)
Open-Label 40 mg
For NASH cirrhosis patients who enter MGL-3196-18 directly or were screen failures from MGL-3196-19, open-label resmetirom 40 mg for up to 66 months.
干预措施: Resmetirom (Drug)
结局指标
主要结局
The effect of once daily, oral administration of resmetirom on the incidence of adverse events.
时间窗: 52 weeks
次要结局
- Percent change in LDL-C from baseline(28 weeks)
- Percent change in the hepatic fat fraction as determined by MRI-PDFF from baseline(52 weeks)