Clinical trial NCT04167358: Linerixibat Long-term Safety, and Tolerability Study
Official title: Long-term Safety and Tolerability Study of Linerixibat for the Treatment of Cholestatic Pruritus in Participants With Primary Biliary Cholangitis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Cholestasis
Keywords: Linerixibat
Cholestasis
Cholestatic pruritus
Primary biliary cholangitis
LLSAT
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2019-11-18
Enrollment: 245
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a non-comparator single group study.
Primary purpose: TREATMENT

Brief summary: This is an open-label, non-comparator, global, multi-center, long-term safety study for evaluating safety and tolerability of linerixibat in participants with cholestatic pruritus in primary biliary cholangitis (PBC) who participated in a prior clinical trial with linerixibat (BAT117123 \[NCT01899703\], 201000 GLIMMER \[NCT02966834\] (group 1) or 212620 GLISTEN \[NCT00210418\]) (group 2). All participants will receive open-label linerixibat for the duration of the study. The study duration is expected to last until the study's end or until linerixibat can be lawfully made available to participants. However, the total duration of study participation will vary by participant depending upon the time of entry relative to study end in their respective country.


Eligibility criteria: Inclusion Criteria:

* Male and female participants must be 18 to 80 years of age inclusive, at the time of signing the informed consent in the participant's parent trial BAT117213, GLIMMER or GLISTEN.
* Participants with a diagnosis of PBC and a history of associated pruritus as evidenced by randomization into a prior eligible linerixibat clinical trial (BAT117213, GLIMMER or GLISTEN).
* Participants must have completed the main treatment period in a prior eligible linerixibat clinical trial (BAT117213, GLIMMER or GLISTEN).
* A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: a) is a woman of non-childbearing potential (WONCBP) or b) is a woman of childbearing potential (WOCBP) and using an acceptable contraceptive method.
* Capable of giving signed informed consent.

Exclusion Criteria:

* Screening total bilirubin \>2x upper limit of normal (ULN).
* Screening alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>6x ULN.
* Screening estimated glomerular filtration rate (eGFR) \<30 milliliters per minute per 1.73 square meter (mL/min/1.73m\^2) based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
* Presence of hepatic decompensation (e.g., variceal bleeds, encephalopathy or ascites).
* Presence of actively replicating viral hepatitis B or C (Viral Hepatitis B \[HBV\], viral Hepatitis C \[HCV\]) infection), primary sclerosing cholangitis (PSC), alcoholic liver disease and/or confirmed hepatocellular carcinoma or biliary cancer.
* Current clinically significant diarrhea in the Investigator's medical opinion.
* Current symptomatic cholelithiasis or cholecystitis.
* Current diagnosis or previous diagnosis of colorectal cancer.
* Any current malignancies (including hematologic and solid malignancies).
* History of bariatric surgery with ileal bypass at any time, or any bariatric surgery performed in the past 3 years.
* Use of Obeticholic acid: within 8 weeks prior to the date of the screening visit and may not restart until after the end of the study or early study withdrawal.
* Administration of any other ileal bile acid transporter (IBAT) inhibitor in the 1 month prior to screening until after the end of the study or early study withdrawal.
* QT interval corrected (QTc) \>480 millisecond (msec) at screening (12-lead ECG)
* Participants with moderate (or greater) alcohol consumption defined as more than one standard drink per day for women and two drinks per day for men.

Primary outcomes:
measure: Number of participants with non-serious adverse events (AEs) and Serious AEs (SAEs)
timeFrame: Up to 66 months
measure: Number of participants with Severe AEs
timeFrame: Up to 66 months
Secondary outcomes:
measure: Change in domain scores of the PBC-40 over time
timeFrame: Baseline and up to 65 months
measure: Change in health-related quality of life (QoL) by the Euro Quality-5 dimension-3 level (EQ-5D-3L) scores over time (Group 1 only)
timeFrame: Baseline and up to 65 months
measure: Change in self-rated health by EQ VAS scores over time (Group 1 only)
timeFrame: Baseline and up to 65 months
measure: Change in the Beck Depression Inventory (BDI-II) scores over time
timeFrame: Baseline and up to 65 months
measure: Number of participants with clinically significant changes in hematology, biochemistry (including lipid and liver parameters), and coagulation parameters
timeFrame: Baseline and up to 65 months
measure: Percentage of responders at Week 24 and Week 52 of continuous treatment (Group 2 only)
timeFrame: Week 24 and Week 52 of continuous treatment
measure: Percentage of participants with maintenance of efficacy at Week 52 of continuous treatment in those that were responders at Week 24 of continuous treatment (Group 2 only)
timeFrame: Week 52 of continuous treatment
measure: Change from Baseline Monthly Sleep Score (MSS) (Group 2 only)
timeFrame: Baseline and up to Week 52 of continuous treatment
measure: Change from Baseline in Monthly Fatigue Score (MFS)(Group 2 only)
timeFrame: Baseline and up to Week 52 of continuous treatment
Other outcomes:
Locations:
city: Davis
country: United States
facility: GSK Investigational Site
state: California
city: West Hollywood
country: United States
facility: GSK Investigational Site
state: California
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Detroit
country: United States
facility: GSK Investigational Site
state: Michigan
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Durham
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Morrisville
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Seattle
country: United States
facility: GSK Investigational Site
state: Washington
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Capital Federal
country: Argentina
facility: GSK Investigational Site
city: Ciudad AutOnoma de Buenos Aire
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autonoma De Bueno
country: Argentina
facility: GSK Investigational Site
city: Rosario
country: Argentina
facility: GSK Investigational Site
city: Santa Fe
country: Argentina
facility: GSK Investigational Site
city: Botucatu
country: Brazil
facility: GSK Investigational Site
city: Brasilia
country: Brazil
facility: GSK Investigational Site
city: Porto Alegre
country: Brazil
facility: GSK Investigational Site
city: Salvador
country: Brazil
facility: GSK Investigational Site
city: Sofia
country: Bulgaria
facility: GSK Investigational Site
city: Edmonton
country: Canada
facility: GSK Investigational Site
state: Alberta
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Beijing
country: China
facility: GSK Investigational Site
city: Beijing
country: China
facility: GSK Investigational Site
city: Changchun
country: China
facility: GSK Investigational Site
city: Chongqing
country: China
facility: GSK Investigational Site
city: Guangzhou
country: China
facility: GSK Investigational Site
city: Nanchang
country: China
facility: GSK Investigational Site
city: Nanjing
country: China
facility: GSK Investigational Site
city: Shanghai
country: China
facility: GSK Investigational Site
city: Tianjin
country: China
facility: GSK Investigational Site
city: Plzen
country: Czechia
facility: GSK Investigational Site
city: Praha 4
country: Czechia
facility: GSK Investigational Site
city: Lille
country: France
facility: GSK Investigational Site
city: Erlangen
country: Germany
facility: GSK Investigational Site
city: Muenster
country: Germany
facility: GSK Investigational Site
city: Haifa
country: Israel
facility: GSK Investigational Site
city: Holon
country: Israel
facility: GSK Investigational Site
city: Jerusalem
country: Israel
facility: GSK Investigational Site
city: Rehovot
country: Israel
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
city: Modena
country: Italy
facility: GSK Investigational Site
city: Monza
country: Italy
facility: GSK Investigational Site
city: Napoli
country: Italy
facility: GSK Investigational Site
city: Negrar Verona
country: Italy
facility: GSK Investigational Site
city: Padova
country: Italy
facility: GSK Investigational Site
city: Palermo
country: Italy
facility: GSK Investigational Site
city: Roma
country: Italy
facility: GSK Investigational Site
city: Chiba
country: Japan
facility: GSK Investigational Site
city: Ehime
country: Japan
facility: GSK Investigational Site
city: Fukui
country: Japan
facility: GSK Investigational Site
city: Gunma
country: Japan
facility: GSK Investigational Site
city: Hiroshima
country: Japan
facility: GSK Investigational Site
city: Hiroshima
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Kagawa
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Nagano
country: Japan
facility: GSK Investigational Site
city: Nagasaki
country: Japan
facility: GSK Investigational Site
city: Nara
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Shizuoka
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Ciudad de MExico
country: Mexico
facility: GSK Investigational Site
city: Mexico City
country: Mexico
facility: GSK Investigational Site
city: Monterrey
country: Mexico
facility: GSK Investigational Site
city: Czestochowa
country: Poland
facility: GSK Investigational Site
city: Katowice
country: Poland
facility: GSK Investigational Site
city: Myslowice
country: Poland
facility: GSK Investigational Site
city: Warszawa
country: Poland
facility: GSK Investigational Site
city: Wroclaw
country: Poland
facility: GSK Investigational Site
city: Kemerovo
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Samara
country: Russian Federation
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Sevilla
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Basingstoke
country: United Kingdom
facility: GSK Investigational Site
city: Glasgow
country: United Kingdom
facility: GSK Investigational Site
city: Hull
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: Newcastle Upon Tyne
country: United Kingdom
facility: GSK Investigational Site
city: Nottingham
country: United Kingdom
facility: GSK Investigational Site
city: Plymouth
country: United Kingdom
facility: GSK Investigational Site
city: Reading Berkshire
country: United Kingdom
facility: GSK Investigational Site
city: Southampton
country: United Kingdom
facility: GSK Investigational Site
city: Surrey
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: