NCT03742973终止2 期
A Randomized, Double-Blind, Placebo-Controlled, Proof-of-Concept Study Evaluating the Efficacy and Safety of Baricitinib (LY3009104) in Patients With Primary Biliary Cholangitis Who Have an Inadequate Response or Are Intolerant to UDCA
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 12
- 主要终点
- Change From Baseline in Alkaline Phosphatase (ALP)
研究概览
简要总结
This study evaluates the safety and efficacy of baricitinib in participants with primary biliary cholangitis (PBC) who do not respond or are unable to take ursodeoxycholic acid (UDCA).
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
- •Have a diagnosis of PBC (consistent with American Association for the Study of Liver Disease (AASLD) and European Association for Study of the Liver (EASL) Practice Guidelines; as demonstrated by the presence of at least 2 of the following 3 diagnostic factors:
- •History of elevated Alkaline Phosphatase (ALP) levels for at least 6 months
- •Positive antimitochondrial antibodies titer
- •Liver biopsy consistent with PBC
- •Have ALP ≥1.67 x ULN but ≤6 x Upper Limit Normal (ULN).
- •Taking UDCA for at least 52 weeks (stable dose for at least 12 weeks) prior to Week 0, or have previously taken, but are intolerant (in the opinion of the investigator) to UDCA and have not received UDCA for at least 12 weeks prior to Week
- •Nonpregnant, nonbreastfeeding female participants of childbearing potential.
排除标准
- •History or presence of other concomitant liver diseases including:
- •Hepatitis C virus (HCV) infection
- •Hepatitis B virus (HBV) infection
- •Primary sclerosing cholangitis
- •Alcoholic liver disease
- •Autoimmune liver disease other than PBC, such as overlap hepatitis
- •Nonalcoholic steatohepatitis
- •Gilbert's syndrome
- •Presence of clinical complications of PBC or clinically significant hepatic decompensation, including:
- •Liver transplantation, current placement on a liver transplant list or current Model for End Stage Liver Disease (MELD) score ≥15
- •Portal hypertension with complications, including known gastric or esophageal varices, ascites, history of variceal bleeds or related therapeutic or prophylactic interventions (e.g., beta blockers, insertion of variceal bands or transjugular intrahepatic portosystemic shunt), or hepatic encephalopathy
- •Cirrhosis, including history or presence of one or more of the following:
- •spontaneous bacterial peritonitis
- •hepatocellular carcinoma
- •Hepatorenal syndrome (type I or II)
- •Have an estimated glomerular filtration rate (eGFR) based on the most recent available serum creatinine of <90 milliliters/minute/1.73 m
- •Have screening electrocardiogram (ECG) abnormalities that in the opinion of the investigator or the sponsor are clinically significant and indicate an unacceptable risk for the participant's participation in the study.
- •Have experienced any of the following within 12 weeks of screening: myocardial infarction, unstable ischemic heart disease, stroke, or New York Heart Association Stage III/IV heart failure.
- •Have a history of venous thromboembolism (VTE) (deep vein thrombosis/pulmonary embolism [DVT/PE]).
- •Have a history or presence of cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematological, neurological, or neuropsychiatric disorders or any other serious and/or unstable illness that, in the opinion of the investigator, could constitute an unacceptable risk when taking investigational product or interfere with the interpretation of data.
- •Have a current or recent (<4 weeks prior to randomization) clinically serious infection or any other active or recent infection that, in the opinion of the investigator, would pose an unacceptable risk to the participant if participating in the study.
- •Have had symptomatic herpes zoster infection within 12 weeks prior to randomization.
- •Have active tuberculosis (TB) disease determined on the basis of a positive medical history, physical examination, or chest radiography (per local standard of care) or latent TB infection (LTBI).
- •Have any of the following specific abnormalities based on screening central lab test results:
- •Hemoglobin <10 grams per deciliter (100.0 grams per liter)
- •Alanine aminotransferase (ALT) >3 x ULN
- •aspartate aminotransferase (AST) >3 x ULN
- •alkaline phosphatase (ALP) >6 x ULN
- •Total bilirubin level (TBL) >ULN
- •Creatine phosphokinase (CPK) > ULN
- •Serum albumin < lower limit of normal (LLN)
- •International Normalized Ratio of Prothrombin Time (INR) > ULN
- •Total white blood cell (WBC) count <LLN
- •Absolute neutrophil count (ANC) <LLN
- •Lymphocyte count <LLN
- •Platelet (thrombocyte) count <LLN
- •Are receiving unstable treatment for pruritus within 6 weeks prior to Week
- •Have been treated with systemic (oral or parenteral) corticosteroids within 6 weeks prior to Week
- •Have received biologic treatments for an immunologic disease within 4 weeks of screening.
- •Have received a Janus kinase (JAK) inhibitor.
- •Have received obeticholic acid.
- •Have received fenofibrate or other fibrates for the treatment of PBC.
研究组 & 干预措施
Baricitinib Cohort A
Experimental
Participants received 2 milligram (mg) of Baricitinib tablet orally once a day for 12 weeks. Cohort A is not reported due to protection of personal identifiable information based on enrollment futility.
干预措施: Baricitinib (Drug)
Placebo Cohort A
Placebo Comparator
Participants received placebo orally once a day for 12 weeks. Cohort A is not reported due to protection of personal identifiable information based on enrollment futility.
干预措施: Placebo (Drug)
Baricitinib Cohort B
Experimental
Participants received 4 mg of Baricitinib orally once a day for 12 weeks. Cohort B was planned, but due to enrollment futility, the strategic decision was made to terminate the study.
干预措施: Baricitinib (Drug)
Placebo Cohort B
Placebo Comparator
Placebo administered orally. Cohort B was planned, but due enrollment futility, the strategic decision was made to terminate the study.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in Alkaline Phosphatase (ALP)
时间窗: Baseline, Week 12
Change from baseline in Alkaline Phosphatase (ALP)
次要结局
- Percentage of Participants With Alkaline Phosphatase (ALP) <1.67 x Upper Limit of Normal (ULN) (and at Least 15% Decrease From Baseline) and Total Bilirubin Level Less Than ULN(Week 12)
- Change From Baseline in Fatigue NRS(Baseline, Week 12)
- Change From Baseline in Itch Numeric Rating Scale (NRS)(Baseline, Week 12)
研究者
研究点 (12)
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