A Study of Baricitinib (LY3009104) in Participants With Primary Biliary Cholangitis Who do Not Respond or Cannot Take UDCA

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Primary Biliary Cholangitis

Intervention / Treatment
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* Drug: Baricitinib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 0. Nonpregnant, nonbreastfeeding female participants of childbearing potential. Exclusion Criteria: 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 m2. 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 0. Have been treated with systemic (oral or parenteral) corticosteroids within 6 weeks prior to Week 0. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Baricitinib Cohort A<br>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. | Drug: Baricitinib<br>* Administered orally.<br>* Other names: LY3009104;|
| Placebo Comparator: Placebo Cohort A<br>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. | Drug: Placebo<br>* Administered orally.<br>|
| Experimental: Baricitinib Cohort B<br>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. | Drug: Baricitinib<br>* Administered orally.<br>* Other names: LY3009104;|
| Placebo Comparator: Placebo Cohort B<br>Placebo administered orally. Cohort B was planned, but due enrollment futility, the strategic decision was made to terminate the study. | Drug: Placebo<br>* Administered orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Alkaline Phosphatase (ALP) | Change from baseline in Alkaline Phosphatase (ALP) | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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 Itch Numeric Rating Scale (NRS) | Change from baseline in itch NRS. The Itch NRS is a participant-administered, 11-point horizontal scale anchored at 0 and 10, with 0 representing no itch and 10 representing worst itch imaginable. Overall severity of a participant's itching is indicated by circling the number that best describes the worst level of itching in the past 7 days. | Baseline, Week 12 | 
| Change From Baseline in Fatigue NRS | Change from baseline in fatigue NRS. The Fatigue NRS is a single-item, patient-administered, 11-point horizontal scale anchored at 0 and 10, with 0 representing no fatigue and 10 representing as bad as you can imagine. Overall severity of a participant's fatigue is indicated by selecting the number that describes the worst level of fatigue during the past 7 days. | Baseline, Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Janus kinase inhibitor, JAK