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

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03742973
• Collaborator: (none)
• Enrollment: 2
• Locations: 12
• Arms: 4
• Actual Duration (Months): 6
• Patients Per Site: 0.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Primary Biliary Cholangitis	Drug: Baricitinib; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official 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
• Actual Study Start Date: Mar 28, 2019
• Actual Primary Completion Date: Sep 26, 2019
• Actual Study Completion Date: Sep 26, 2019

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Alkaline Phosphatase (ALP) [Baseline, Week 12]

   Change from baseline in Alkaline Phosphatase (ALP)

Secondary Outcome Measures

1. 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]

   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.

2. Change From Baseline in Itch Numeric Rating Scale (NRS) [Baseline, Week 12]

   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.

3. Change From Baseline in Fatigue NRS [Baseline, Week 12]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: 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 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.

Contacts and Locations

Locations

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

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: 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), Eli Lilly and Company

Study Documents (Full-Text)

• Study Protocol - Apr 24, 2019
• Statistical Analysis Plan - May 14, 2019

More Information

Additional Information:

• 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

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT03742973
• Other Study ID Numbers: 17039; I4V-MC-JAIV
• First Posted: Nov 15, 2018
• Last Update Posted: Oct 14, 2020
• Last Verified: Oct 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Eli Lilly and Company: Janus kinase inhibitor; JAK
• Additional relevant MeSH terms: Cholangitis; Liver Cirrhosis, Biliary

Study Results

Participant Flow

Pre-assignment Detail	Zero participants reported in cohort A due to protection of personal identifiable information based on enrollment futility and cohort B is not reported due to early study termination based on enrollment futility.

Arm/Group Title	Baricitinib Cohort A	Placebo Cohort A
Arm/Group Description	Participants received 2 milligram (mg) of Baricitinib tablet orally once a day for 12 weeks.	Participants received placebo orally once a day for 12 weeks.
Period Title: Overall Study
STARTED	0	0
COMPLETED	0	0
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Placebo Cohort A	.Baricitinib Cohort A	Total
Arm/Group Description	Participants received placebo orally once a day for 12 weeks.	Participants received 2 mg of Baricitinib tablet orally once a day for 12 weeks.	Total of all reporting groups
Overall Participants	0	0	0
Age () []
<=18 years
Between 18 and 65 years
>=65 years
Sex: Female, Male () []
Female
Male
Ethnicity (NIH/OMB) () []
Hispanic or Latino
Not Hispanic or Latino
Unknown or Not Reported
Race (NIH/OMB) () []
American Indian or Alaska Native
Asian
Native Hawaiian or Other Pacific Islander
Black or African American
White
More than one race
Unknown or Not Reported
Region of Enrollment () []
Baseline in ALP (microgram/Liter (u/L)) []

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Alkaline Phosphatase (ALP)
Description	Change from baseline in Alkaline Phosphatase (ALP)
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Zero participants reported in cohort A due to protection of personal identifiable information based on enrollment futility.

Arm/Group Title	Baricitinib Cohort A	Placebo Cohort A
Arm/Group Description	Participants received 2 mg of Baricitinib tablet orally once a day for 12 weeks.	Participants received placebo orally once a day for 12 weeks.
Measure Participants	0	0

2. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

Zero participants with evaluable data was reported in cohort A due to protection of personal identifiable information based on enrollment futility.

Arm/Group Title	Baricitinib Cohort A
Arm/Group Description	Participants received 2 mg of Baricitinib tablet orally once a day for 12 weeks.
Measure Participants	0

3. Secondary Outcome

Title	Change From Baseline in Itch Numeric Rating Scale (NRS)
Description	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.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Zero participants reported in cohort A due to protection of personal identifiable information based on enrollment futility.

Arm/Group Title	Baricitinib Cohort A	Placebo Cohort A
Arm/Group Description	Participants received 2 mg of Baricitinib tablet orally once a day for 12 weeks.	Participants received placebo orally once a day for 12 weeks.
Measure Participants	0	0

4. Secondary Outcome

Title	Change From Baseline in Fatigue NRS
Description	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.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Zero participants reported in cohort A due to protection of personal identifiable information based on enrollment futility.

Arm/Group Title	Baricitinib Cohort A	Placebo Cohort A
Arm/Group Description	Participants received 2 mg of Baricitinib tablet orally once a day for 12 weeks.	Participants received placebo orally once a day for 12 weeks.
Measure Participants	0	0

Adverse Events

Time Frame	Up to 6 Months
Adverse Event Reporting Description	Zero participants reported in cohort A due to protection of personal identifiable information based on enrollment futility and cohort B is not reported due to early study termination based on enrollment futility.
Arm/Group Title	Baricitinib Cohort A		Placebo Cohort A
Arm/Group Description	Participants received 2 mg of Baricitinib tablet orally once a day for 12 weeks.		Participants received placebo orally once a day for 12 weeks.
All Cause Mortality
	Baricitinib Cohort A		Placebo Cohort A
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Serious Adverse Events
	Baricitinib Cohort A		Placebo Cohort A
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Baricitinib Cohort A		Placebo Cohort A
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

Zero participants reported in cohort A due to protection of personal identifiable information based on enrollment futility and cohort B is not reported due to early study termination based on enrollment futility.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.