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

Phase 1

Conditions: Primary Biliary Cholangitis
MedDRA version: 20.0Level: PTClassification code 10008604Term: CholangitisSystem Organ Class: 10019805 - Hepatobiliary disorders
Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Registration Number: EUCTR2018-003365-34-IT

Lead Sponsor: ELI LILLY & COMPANY, LILLY CORPORATE CENTER

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 2

Inclusion Criteria

Type of Patient and Disease Characteristics
[1] Male or female patients who are at least 18 years of age.
[2] 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; [Lindor 2009; EASL 2017]), 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
[3] Have ALP =1.67 x ULN but <6 x ULN
[4] Taking UDCA for at least 52 weeks (stable dose for at least 12
weeks) prior to Visit 3
(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 Visit 3 (Week 0).
Patient Characteristics
[5] Nonpregnant, nonbreastfeeding female patients of childbearing
potential:
a. Patients who are abstinent (if this is complete abstinence, as their
preferred and usual lifestyle) or in a same-sex relationship (as part of
their
preferred and usual lifestyle) must agree to either remain abstinent or
stay in a same-sex relationship without sexual relationships with the
opposite sex during the entirety of the study and for at least 1 week
following the last dose of investigational product.
Total abstinence is defined as refraining from intercourse during the
entirety of the study and for at least 1 week following the last dose of
investigational product. Periodic abstinence such as calendar, ovulation,
symptothermal, postovulation methods, and withdrawal are not
acceptable methods of contraception b. Otherwise, patients must agree
to use for the entirety of the study and for at least 1 week following the
last dose of investigational product, 2
effective methods of contraception, where at least 1 form is highly
effective (such as combination oral contraceptives, implanted
contraceptives or
intrauterine devices). Effective contraception (such as male or female
condoms with
spermicide, diaphragms with spermicide or cervical sponges) may be
used as the second therapy. Barrier protection methods without
concomitant
use of a spermicide are not a reliable or acceptable method.
Female patients of nonchildbearing potential may participate without
requirements for contraception. This includes female patients who are:
a. Infertile due to surgical sterilization (hysterectomy, bilateral
oophorectomy,
or tubal ligation), congenital anomaly such as mullerian agenesis; or
b. Postmenopausal – defined as either
i. A woman at least 50 years of age with an intact uterus, not on
hormone therapy, who has had either
1. Cessation of menses for at least 1 year, or
2. At least 6 months of spontaneous amenorrhea with a
follicle-stimulating hormone (FSH) >40 mIU/mL; or
ii. A woman 55 years of age or older not on hormone therapy, who
has had at least 6 months of spontaneous amenorrhea; or
iii. A woman at least 55 years of age with a diagnosis of menopause
prior to starting hormone replacement therapy.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 52
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

[7] History or presence of other concomitant liver diseases including:
a. Hepatitis C virus (HCV) infection (hepatitis C antibody-positive and
HCV ribonucleic acid [RNA] positive). ¿ Note: Patients who have
documented anti-HCV treatment for a past HCV infection AND are HCV
RNA-negative with a sustained viral response may be enrolled in the
study.
b. Hepatitis B virus (HBV) infection defined as:
¿ positive for hepatitis B surface antigen (HBsAg), or
¿ positive for hepatitis B core antibody (HBcAb)
c. Primary sclerosing cholangitis
d. Alcoholic liver disease
e. Autoimmune liver disease other than PBC, such as overlap hepatitis
f. Nonalcoholic steatohepatitis
g. Gilbert's syndrome
[8] Presence of clinical complications of PBC or clinically significant
hepatic decompensation, including:
a. Liver transplantation, current placement on a liver transplant list or
current Model for End Stage Liver Disease (MELD) score = 15
b. 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
c. Cirrhosis, including history or presence of one or more of the
following: spontaneous bacterial peritonitis, hepatocellular carcinoma
d. Hepatorenal syndrome (type I or II)
[9] Have an estimated glomerular filtration rate (eGFR) based on the
most recent available serum creatinine of <90 mL/min/1.73 m2.
[10] 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 patient's participation in the study.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the effect of baricitinib 4-mg QD compared to placebo on PBC disease;Secondary Objective: To evaluate the effect of baricitinib 2-mg QD compared to placebo on PBC disease<br>To evaluate the effect of baricitinib 4-mg and 2-mg QD compared to placebo on PBC symptoms;Primary end point(s): Change from baseline in ALP;Timepoint(s) of evaluation of this end point: at Week 12

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Proportion of patients with ALP <1.67 x ULN (and at least 15% decrease from baseline) and total bilirubin<ULN<br>Change from baseline in itch as measured by Itch NRS<br>Change from baseline in fatigue as measured by Fatigue NRS;Timepoint(s) of evaluation of this end point: Week 12

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