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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03742973
• Date of registration: 14/11/2018
• Prospective Registration: Yes
• Primary sponsor: Eli Lilly and Company
• Public title: A Study of Baricitinib (LY3009104) in Participants With Primary Biliary Cholangitis Who do Not Respond or Cannot Take UDCA
• Scientific title: 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
• Date of first enrolment: March 28, 2019
• Target sample size: 2
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT03742973
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 2

Countries of recruitment

Italy, Puerto Rico, United Kingdom, United States

Contacts

• Name: Call 1-877-CTILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
• Affiliation: Eli Lilly and Company

Key inclusion & exclusion criteria

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
- Absolute neutrophil count (ANC)
- Lymphocyte count
- Platelet (thrombocyte) count
- 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Primary Biliary Cholangitis

Intervention(s)

Drug: Baricitinib

Drug: Placebo

Primary Outcome(s)

Change From Baseline in Alkaline Phosphatase (ALP) [Time Frame: Baseline, Week 12]

Secondary Outcome(s)

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 [Time Frame: Week 12]

Change From Baseline in Itch Numeric Rating Scale (NRS) [Time Frame: Baseline, Week 12]

Change From Baseline in Fatigue NRS [Time Frame: Baseline, Week 12]

Secondary ID(s)

17039

I4V-MC-JAIV

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 14/10/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03742973