A Prospective, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Resmetirom for the Treatment of Patients with Non-Alcoholic Steatohepatitis with Moderate to Advanced Liver Fibrosis
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 206
- 试验地点
- 14
- 主要终点
- Proportion of patients achieving NASH resolution with no worsening of fibrosis
研究概览
简要总结
This will be a phase III, Prospective, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Efficacy and Safety of Resmetirom for the Treatment of Patients with Non-Alcoholic Steatohepatitis with Moderate to Advanced Liver Fibrosis. Approximately 206 patients (103 patients in each arm) will be enrolled in the study from various parts of India. The study will be initiated only after the receipt of Regulatory and Ethics committee (EC) approvals. The patients, investigators who will assess the patients for efficacy and safety, and the Pathologists who will assess the Liver Biopsy Specimens will be blinded to treatment allocation. After signing the informed consent document (ICD), patients will be screened by undergoing various assessments as mentioned in Schedule of Assessments,
Total screening period is up to 5 weeks (Step 1- Up to 1 week, Step 2 Up to 4 weeks). Patients will be provided the screening diary at Step 1 Screening visit to record details of any adverse events or any medications taken. Patients will be required to bring completed visit diary at Step 2 Screening visit. If patient is eligible for Step 2, the screening diary will be returned to the patients and will be retrieved at the Baseline/Randomization Visit.
After confirming eligibility at Visit 3 (Baseline / randomization visit), The randomization will be stratified by type-2 diabetes status (presence/absence) and fibrosis stage (2, or 3) on liver biopsy at screening visit. Patients will receive either Resmetirom 60 mg, 80 mg or 100 mg Tablets, once daily for 52 Weeks as a test product or Placebo of Resmetirom 60 mg, 80 mg or 100 mg Tablets, once daily for 52 Weeks as a comparator product. Test product will be administered once daily (preferably at the evening time), with or without meals. Patients will be advised to take the medication preferably at same time
At each visit, from Visit 3 to Visit 12, participants will be given diaries to record details of study medication administration (to be recorded only till Visit 11), AEs, concomitant medications, and diet/exercise control. Participants will be required to bring completed visit diaries at each visit, Liver biopsies will be performed for all eligible patients at Screening Visit (Step 2) and at EOT (Week 52) visit.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Double
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- All
入选标准
- •Patients of either gender with age between 18 to 65 years (both inclusive) and willing to provide written informed consent.
- •Who do not have any history of significant alcohol consumption
- •Have at least 3 metabolic risk factors
- •Biopsy-proven Diagnosis of NASH based on a liver biopsy with fibrosis stage 2, or 3 on liver biopsy and NAS of greater than or equal to 4
- •Women of childbearing potential must have a negative urine pregnancy test at Screening and Randomization and agree to use highly effective methods of contraception to prevent pregnancy from study entry till end of study
- •Male patients must have had a successful vasectomy (confirmed azoospermia) or they and their female partners should be practicing highly effective contraception throughout the study period.
排除标准
- •History of significant alcohol consumption 2) Regular use of drugs historically associated with NAFLD 3) Thyroid diseases 4) History of bariatric surgery or intestinal bypass surgery within the 5 years prior to randomization or planned during the conduct of the study.
- •Weight gain or loss of greater than or equal to 5% total body weight within 12 weeks prior to randomization.
- •Type 2 diabetes patients with HbA1c greater than or equal to 9.0%.
- •Glucagon-like peptide 1 [GLP-1] agonist therapy.
- •Use of high dose vitamin E 9) Presence of cirrhosis on liver biopsy defined as stage 4 fibrosis.
- •Diagnosis of hepatocellular carcinoma (HCC).
- •Hepatic decompensation 12) Patients with other chronic liver diseases 13) Patients having an active autoimmune disease, 14) Inability to safely obtain a liver biopsy.
- •Hypersensitivity to Resmetirom or to any of the excipients in study medications.
结局指标
主要结局
Proportion of patients achieving NASH resolution with no worsening of fibrosis
时间窗: [Timeframe: Week 52] | week 52
次要结局
- Efficacy(Proportion of MRI-PDFF Responders (patients achieving greater than or equal to 30% relative reduction in hepatic)
- Additional NAS and Fibrosis endpoints on Liver biopsy
- Change from baseline in Serum ALT, AST, GGT and ALP([Timeframe: Baseline, Weeks 24,52])
- Change from baseline in Serum total cholesterol, LDL Cholesterol, HDL Cholesterol, VLDL cholesterol and triglycerides([Timeframe: Baseline, Weeks 24, 52])
- Change from baseline in FibroScan LSM score([Timeframe: Baseline, Weeks 24 and 52])
- Change from baseline in FibroScan CAP score([Timeframe: Baseline, Weeks 24 and 52])
- Proportion of patients with a greater than or equal to30% reduction in FibroScan LSM score([Timeframe: Weeks 24 and 52])
- Change from baseline in SF-36 score([Timeframe: Baseline, Weeks 24 and 52])
- Safety:(Number and proportion of patients with treatment emergent adverse events (TEAEs) and Serious Adverse Events (SAEs))
研究者
Dr Pravin Ghadge
Sun Pharma Laboratories Limited