A Multicenter, Randomized, Double blind, Parallel Group, Placebo Controlled, Phase III Clinical Study to Evaluate the Efficacy, Safety and Tolerability of Resmetirom Tablets versus Placebo Tablets in adult participants in conjunction with diet and exercise for the treatment in Non-cirrhotic Non-alcoholic Steatohepatitis (NASH) with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis).
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 210
- 试验地点
- 25
- 主要终点
- Proportion with resolution of NASH (ballooning 0, inflammation 0,1) associated with at least 2-point reduction in NAFLD Activity Score (NAS) without worsening of fibrosis stage from baseline to end of study visit (Week 52).
研究概览
简要总结
A Multicenter, Randomized, Double Blind, Parallel Group, Placebo Controlled, Phase III Clinical Study to Evaluate the Efficacy, Safety and Tolerability of Resmetirom Tablets versus Placebo Tablets in adult participants in conjunction with diet and exercise for the treatment in Non-cirrhotic Non-alcoholic Steatohepatitis (NASH) with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis).
Primary objective:
To evaluate the efficacy of Resmetirom Tablets in adult participants in conjunction with diet and exercise for the treatment in Non cirrhotic Non-alcoholic Steatohepatitis (NASH) with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis).
Secondary objective:
To evaluate the safety and tolerability of Resmetirom Tablets in adult participants in conjunction with diet and exercise for the treatment in Non-cirrhotic Non-alcoholic Steatohepatitis (NASH) with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis).
Lifestyle modification with diet and exercise is to be followed for all the three cohorts.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- All
入选标准
- •Male or Female participants greater than or equal to 18 years to less than or equal to 65 years.
- •Confirmed diagnosis of NASH fibrosis in participants who meet one of the following criteria that is consistent with NASH liver fibrosis: Historical biochemical test for fibrosis: N-terminal pro-peptide of type III collagen (PRO-C3) greater than 14 ng/mL or Enhanced liver fibrosis (ELF) greater than or equal to 9 or Fibroscan with transient elastography greater than or equal to 8.5 kPa and controlled attenuation parameter grater than or equal to 280 dB.m-
- •Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) greater than or equal to 8% obtained during the screening period.
- •Biopsy-proven NASH (baseline liver biopsy), based on a liver biopsy obtained within 3 months of randomization with fibrosis stage, F2 or F3 on liver biopsy and NAS of greater than or equal to 4 with a score of at least 1 in each of the following NAS components: -Steatosis (scored 0 to 3) -Ballooning degeneration (scored 0 to 2) -Lobular inflammation (scored 0 to 3)
- •Participants who are willing to give informed consent for participation in the study and willing to adhere to all protocol procedures.
- •Cohort specific Inclusion Criteria: Cohort I: Participants with a body weight of less than 60 kg.
- •Cohort II: Participants with a body weight between 60 to less than 100 kg.
- •Cohort III: Participants with a body weight of greater than or equal to 100 kg.
排除标准
- •1.Participants with a history of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to screening.
- •Participants with regular use of drugs historically associated with NAFLD.
- •Participants with presence of cirrhosis on liver biopsy defined as stage 4 fibrosis (F4).
- •Participants with diagnosis of hepatocellular carcinoma (HCC).
- •Participants with hepatic decompensation.
- •Participants with chronic liver diseases other than NASH.
- •Participants whose Serum ALT greater than 250 U/L.
- •Participants with a diagnosis of type 2 diabetes mellitus with glycosylated hemoglobin (HbA1c) greater than or equal to 11.0%.
- •Participants with Estimated glomerular filtration rate (eGFR)less than 60 mL/min/1.73 m2 [using the Modification of Diet in Renal Disease (MDRD) equation] at screening.
- •Participants with Thyroid diseases:.
- •Active hyperthyroidism.
- •Untreated clinical hypothyroidism defined by thyroid stimulating hormone (TSH) greater than 7 IU/L with symptoms of hypothyroidism or greater than 10 IU/L without symptoms.
- •Participants who have had a thyroidectomy and are on replacement thyroxine doses greater than 75 µg per day are allowed.
- •Participants with known history of HIV, Hepatitis B and Hepatitis C.
- •Participants with history of any active autoimmune disease.
- •Participants with significant cardiovascular history defined as: myocardial infarction, unstable angina pectoris, transient ischemic attack, unstable or previously undiagnosed arrhythmia, cardiac surgery or revascularization (coronary angioplasty or bypass grafts), or cerebrovascular accident.
- •Participants with clinically relevant current or past history of severe, unstable, or uncontrolled pulmonary, hepatic and renal diseases.
- •Participants with history of bariatric surgery or intestinal bypass surgery within the 5 years prior to screening or planned during the conduct of the study.
- •Currently taking prohibited concomitant medications listed and inability/unwillingness to discontinue them for the entire study period.
- •Participants with active, serious medical disease with a likely life expectancy less than 2 years.
- •Any other health or mental condition or any significant laboratory parameters that in the investigators opinion may adversely affect the participants ability to complete the study or its measures or that may pose significant risk to the participant.
- •Concurrent participation in another clinical trial or any investigational therapy within 30 days prior to signing informed consent.
- •Female participants who are pregnant or lactating or planning to become pregnant during the study period. Females or males who are not ready to use acceptable contraceptive methods during the course of study.
结局指标
主要结局
Proportion with resolution of NASH (ballooning 0, inflammation 0,1) associated with at least 2-point reduction in NAFLD Activity Score (NAS) without worsening of fibrosis stage from baseline to end of study visit (Week 52).
时间窗: 52 Weeks (364 Days)
Proportion with at least a 1-point improvement in fibrosis stage with no worsening of NAS from baseline to end of study visit (Week 52).
时间窗: 52 Weeks (364 Days)
次要结局
- Percentage change in the low-density lipoprotein from baseline to end of study visit (Week 52).
- Safety Parameter:(The assessment of safety will be based on the frequency of Adverse Events and Changes in laboratory parameters.)
研究者
Dr Dawesh Prakash Yadav
Institute of Medical Sciences, Banaras Hindu University