Clinical trial NCT04950127: Global Linerixibat Itch Study of Efficacy and Safety in Primary Biliary Cholangitis (PBC) (GLISTEN)
Official title: A Two-part, Randomized, Placebo Controlled, Double Blind, Multicenter, Phase 3 Study to Evaluate the Efficacy and Safety of Linerixibat for the Treatment of Cholestatic Pruritus in Participants With Primary Biliary Cholangitis (PBC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pruritus
Keywords: Cholestasis
GLISTEN
GSK2330672
Itch
Primary biliary cholangitis
Pruritus
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2021-07-06
Enrollment: 238
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized to receive linerixibat and/or placebo during the study.
Primary purpose: TREATMENT

Brief summary: This is a 2-part study in PBC participants with cholestatic pruritus and will evaluate the efficacy, safety and impact on health-related quality of life of linerixibat compared with placebo.


Eligibility criteria: Inclusion Criteria:

* Male and female participants must be between 18 to 80 years of age inclusive, at the time of signing the informed consent.
* Participants who have documented PBC.
* Participants who have moderate to severe itch.

Exclusion Criteria:

* Total bilirubin \>2.0 times Upper Limit of Normal (ULN) using the average of two Baseline measures.
* Screening Alanine Aminotransferase (ALT) \> 6 times ULN in a single Baseline measure or ALT \> 5 times ULN using the average of two Baseline measures.
* Screening estimated glomerular filtration rate (eGFR) \<30 milliliter per minute per 1.73 square meter (mL/min/1.73m\^2).
* History or presence of hepatic decompensation (e.g., variceal bleeding, hepatic encephalopathy or ascites).
* Presence of HBsAg positive hepatitis B or hepatitis C (HCV) (anti-HCV and Ribonucleic acid \[RNA\] detected) infection, primary sclerosing cholangitis (PSC), alcoholic liver disease and/or confirmed hepatocellular carcinoma or biliary cancer.
* Current clinically significant diarrhea or active inflammatory ileal disease according to Investigator´s clinical judgment.
* Current symptomatic cholelithiasis or cholecystitis.
* Current diagnosis of primary skin disorders with itch as a characteristic feature (e.g., atopic dermatitis, psoriasis).
* Primary sleep disorders such as but are not limited to sleep apnea, narcolepsy, hypersomnia.
* Initiation, discontinuation or change in dose of ursodeoxycholic acid (UDCA), bezafibrate or fenofibrate in the 8 weeks prior to Screening.
* Use of obeticholic acid: within 8 weeks prior to Screening. (Participants may not initiate or restart during the study).
* Initiation, discontinuation, or change in dose of any of the following in the 8 weeks prior to Screening: bile acid binding resins, rifampicin, naltrexone, naloxone, nalfurafine, pregabalin, gabapentin, sertraline or other selective serotonin reuptake inhibitor (SSRIs), antihistamines used for the treatment of itching.
* Administration of any other human ileal bile acid transporter (IBAT) inhibitor in the 12 weeks prior to screening.
* Any planned procedures intended to treat cholestatic pruritus such as nasobiliary drainage or ultraviolet light therapy from Screening and throughout the study.
* History of sensitivity or intolerance to the study treatment.

Primary outcomes:
measure: Change from Baseline in Monthly Itch Scores over 24 weeks using Numerical Rating Scale (NRS)
timeFrame: Baseline and up to 24 weeks
Secondary outcomes:
measure: Change from Baseline in Weekly Itch Score at Week 2
timeFrame: Baseline and Week 2
measure: Change from Baseline in Monthly Sleep Score as measured by NRS over 24 weeks
timeFrame: Baseline and up to 24 weeks
measure: Number of participants achieving a >=2-point reduction from Baseline in the Monthly Itch Score at Week 24
timeFrame: Baseline and Week 24
measure: Number of participants achieving a >=3-point reduction from Baseline in the Monthly Itch Score at Week 24
timeFrame: Baseline and Week 24
measure: Number of participants as achieving a >=4-point reduction from Baseline in the Monthly Itch Score at Week 24
timeFrame: Baseline and Week 24
measure: Change from Baseline in Patient's Global Impression of Severity (PGI-S) over 24 weeks
timeFrame: Baseline and up to 24 weeks
measure: Patient's Global Impression of Change (PGI-C) scores over 24 weeks
timeFrame: Up to 24 weeks
measure: Change from Baseline in Primary Biliary Cholangitis-40 (PBC-40) domain scores at Week 24
timeFrame: Baseline and Week 24
measure: Change from Baseline in alkaline phosphatase (ALP) at Week 24
timeFrame: Baseline and Week 24
measure: Change from Baseline in bilirubin at Week 24
timeFrame: Baseline and Week 24
Other outcomes:
Locations:
city: Davis
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: San Francisco
country: United States
facility: GSK Investigational Site
state: California
city: Colorado Springs
country: United States
facility: GSK Investigational Site
state: Colorado
city: Hialeah
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Detroit
country: United States
facility: GSK Investigational Site
state: Michigan
city: Jackson
country: United States
facility: GSK Investigational Site
state: Mississippi
city: Omaha
country: United States
facility: GSK Investigational Site
state: Nebraska
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: Columbus
country: United States
facility: GSK Investigational Site
state: Ohio
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
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: San Nicolas
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city: Santa Fe
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facility: GSK Investigational Site
city: Gent
country: Belgium
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: Plovdiv
country: Bulgaria
facility: GSK Investigational Site
city: Sofia
country: Bulgaria
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: Zhanjiang
country: China
facility: GSK Investigational Site
city: Ostrava
country: Czechia
facility: GSK Investigational Site
city: Plzen
country: Czechia
facility: GSK Investigational Site
city: Praha 4
country: Czechia
facility: GSK Investigational Site
city: CrEteil Cedex
country: France
facility: GSK Investigational Site
city: Grenoble Cedex 9
country: France
facility: GSK Investigational Site
city: Lille
country: France
facility: GSK Investigational Site
city: Paris
country: France
facility: GSK Investigational Site
city: Erlangen
country: Germany
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city: Essen
country: Germany
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city: Muenster
country: Germany
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city: Athens
country: Greece
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city: Beer-Sheva
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city: Haifa
country: Israel
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city: Holon
country: Israel
facility: GSK Investigational Site
city: Jerusalem
country: Israel
facility: GSK Investigational Site
city: Nahariya
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: Palermo
country: Italy
facility: GSK Investigational Site
city: Roma
country: Italy
facility: GSK Investigational Site
city: Rozzano MI
country: Italy
facility: GSK Investigational Site
city: Ehime
country: Japan
facility: GSK Investigational Site
city: Fukui
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: Ibaraki
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: 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: 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: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Novosibirsk
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: Basingstoke
country: United Kingdom
facility: GSK Investigational Site
city: Cambridge
country: United Kingdom
facility: GSK Investigational Site
city: Durham
country: United Kingdom
facility: GSK Investigational Site
city: Hull
country: United Kingdom
facility: GSK Investigational Site
city: Liverpool
country: United Kingdom
facility: GSK Investigational Site
city: London
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: 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: