AFFIRM: A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Effect of Seladelpar on Clinical Outcomes in Patients With Primary Biliary Cholangitis (PBC) and Compensated Cirrhosis
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 402
- 试验地点
- 320
- 主要终点
- Event Free Survival (EFS)
研究概览
简要总结
The goal of this clinical study is to learn more about the study drug, seladelpar, and its effects on clinical outcomes in participants with primary biliary cholangitis (PBC) and compensated cirrhosis.
The primary objective of this study is to evaluate the effect of seladelpar compared to placebo on EFS. EFS is defined as the time from start of treatment to the first occurrence of any of the following adjudicated events up to Week 156.
详细描述
To Evaluate the Effect of Seladelpar on Clinical Outcomes in Patients with Primary Biliary Cholangitis (PBC) and Compensated Cirrhosis.
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
- Double (Participant, Investigator)
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
- •Individuals must meet the following criteria to be eligible for study participation:
- •Must be at least 18 years old.
- •Must have a confirmed prior diagnosis of primary biliary cholangitis (PBC)
- •Evidence of cirrhosis
- •CP Score A or B
- •Females of reproductive potential must use at least 1 barrier contraceptive and a second effective birth control method during the study and for at least 90 days after the last dose. Male individuals who are sexually active with female partners of reproductive potential must use barrier contraception, and their female partners must use a second effective birth control method during the study and for at least 90 days after the last dose
- •Individuals must be able to comply with the instructions for study drug administration and be able to complete the study schedule of assessments (SOA)
排除标准
- •Individuals must not meet any of the following criteria to be eligible for study participation:
- •Prior exposure to seladelpar
- •A medical condition other than PBC that, in the Investigator's opinion, would preclude full participation in the study
- •History of liver transplantation or actively listed for cadaveric or planned living donor transplant.
- •Decompensated cirrhosis
- •Evidence of portal vein thrombosis based on imaging at time of Screening by Doppler ultrasound or prior evidence by CT or MRI
- •Hospitalization for liver-related complication within 12 weeks of Screening
- •Laboratory parameters at Screening:
- •Alkaline phosphatase (ALP) < 1.5× Upper limit of normal (ULN) or ≥ 10×ULN
- •Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) ≥5×ULN
- •Total bilirubin (TB) ≤ 0.6 × ULN or ≥ 5 × ULN
- •Platelet count ≤50×10^3/µL
- •Albumin ≤2.8 g/dL
- •Estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m^2
- •MELD score >
- •For individuals on anticoagulation medication, baseline International normalized ratio (INR) determination for MELD score calculation should take anticoagulant use into account, in consultation with the Medical Monitor.
- •Serum alpha-fetoprotein (AFP) >20 ng/mL
- •CP-C cirrhosis
- •History or presence of other concomitant liver diseases
研究组 & 干预措施
Placebo
Participants with CP-A or CP-B will be randomized to received placebo to match one capsule daily for up to 36 months.
干预措施: Placebo (Drug)
Open Label Extension Phase
Participants with CP-A who remained on the study drug at week 156 will receive seladelpar 10 mg daily or participants with CP-B will received seladelpar 5 mg daily for a maximum of 3 years.
干预措施: Seladelpar (Drug)
Seladelpar
Participants with Child-Pugh (CP)-A cirrhosis will receive seladelpar 10 mg orally once daily or participants with CP-B cirrhosis will receive seladelpar 5 mg orally once daily, for up to 36 months.
干预措施: Seladelpar (Drug)
结局指标
主要结局
Event Free Survival (EFS)
时间窗: 36 months
EFS is defined as measured by the time from start of treatment to the first occurrence of any of the following clinical events: 1. Death by any cause 2. Liver transplantation 3. MELD score ≥15 4. Ascites requiring treatment 5. Hospitalization for any of the following 1. Esophageal or gastric variceal bleeding 2. Hepatic encephalopathy 3. Spontaneous bacterial peritonitis
次要结局
- Time to Event Free Survival (EFS)(36 months)
- Overall survival(36 months)
- Liver transplant-free survival(36 months)
- Time to hospitalization(36 months)
- Overall Survival (OS)(36 months)
- Liver Transplant-Free Survival (LTFS)(36 months)
- Time to Hospitalization(36 months)
- Time to Each Type of Adjudicated PBC Clinical Event: Model for End-Stage Liver Disease (MELD) score ≥ 15(36 months)
- Time to Each Type of Adjudicated PBC Clinical Event: Ascites Requiring Treatment(36 months)