Primary Biliary Cholangitis MedDRA version: 20.0 Level: PT Classification code 10008604 Term: Cholangitis System Organ Class: 10019805 - Hepatobiliary disorders
Conditions
Interventions
Product Name: Olumiant
Product Code: LY3009104
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: BARICITINIB
Other descriptiv
Sponsors
Eli Lilly and Company
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects will be eligible for randomization only if they meet all of the following criteria within the screening period, which is =49 days prior to randomization, unless specifically defined: 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,
Exclusion criteria
Exclusion criteria: Medical Conditions [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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 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
| Measure | Time frame |
|---|---|
| Secondary end point(s): Proportion of patients with ALP <1.67 x ULN (and at least 15% decrease from baseline) and total bilirubin<ULN Change from baseline in itch as measured by Itch NRS Change from baseline in fatigue as measured by Fatigue NRS ;Timepoint(s) of evaluation of this end point: at Week 12 | — |
Countries
Italy, United Kingdom, United States
Contacts
Public ContactClinical Trial Registry Office
Eli Lilly
Outcome results
None listed