Purpose

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).

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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 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 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 Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Baricitinib Low Dose Cohort A
Baricitinib administered orally.
  • Drug: Baricitinib
    Administered orally.
    Other names:
    • LY3009104
Placebo Comparator
Placebo Cohort A
Placebo administered orally.
  • Drug: Placebo
    Administered orally.
Experimental
Baricitinib High Dose Cohort B
Baricitinib administered orally.
  • Drug: Baricitinib
    Administered orally.
    Other names:
    • LY3009104
Placebo Comparator
Placebo Cohort B
Placebo administered orally.
  • Drug: Placebo
    Administered orally.

Recruiting Locations

Tulane University School of Medicine
New Orleans, Louisiana 70112
Contact:
504-988-5344

More Details

NCT ID
NCT03742973
Status
Recruiting
Sponsor
Eli Lilly and Company

Study Contact

There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or
1-317-615-4559
clinicaltrials.gov@lilly.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.