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

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

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).

Study Overview

• Status: Terminated
• Conditions: Primary Biliary Cholangitis
• Intervention / Treatment: Drug: Placebo; Drug: Baricitinib

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00936
    • University of Puerto Rico, Medical Sciences Campus
  • San Juan, Puerto Rico, 00909
    • Klinical Investigations Group, LLC
• United States
  • California
    • Coronado, California, United States, 92118
      • Southern California GI and Liver Centers (SCLC)
    • Sacramento, California, United States, 95817
      • University of California, Davis - Health Systems
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado School of Medicine
  • Florida
    • Miami, Florida, United States, 33136
      • Schiff Center for Liver Diseases/University of Miami
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • The Institute for Digestive Health and Liver Disease at Mercy
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • New York
    • New York, New York, United States, 10016
      • NYU Langone
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • UH Cleveland Medical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

Helpful Links

• Click here for more information about this study: A Study of Baricitinib (LY3009104) in Participants With Primary Biliary Cholangitis Who do Not Respond or Cannot Take UDCA

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2019
• Primary Completion (Actual): September 26, 2019
• Study Completion (Actual): September 26, 2019

Study Registration Dates

• First Submitted: November 14, 2018
• First Submitted That Met QC Criteria: November 14, 2018
• First Posted (Actual): November 15, 2018

Study Record Updates

• Last Update Posted (Actual): October 14, 2020
• Last Update Submitted That Met QC Criteria: September 18, 2020
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: JAK; Janus kinase inhibitor
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Biliary Tract Diseases; Bile Duct Diseases; Cholestasis, Intrahepatic; Cholestasis; Liver Cirrhosis; Cholangitis; Liver Cirrhosis, Biliary
• Other Study ID Numbers: 17039; I4V-MC-JAIV (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• IPD Sharing Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No