Global Linerixibat Itch Study of Efficacy and Safety in Primary Biliary Cholangitis (PBC) (GLISTEN)

Pruritus Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04950127
• Other study ID #: 212620
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: August 27, 2021
• Est. completion date: January 8, 2025

Study information

• Verified date: May 2024
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 241
• Est. completion date: January 8, 2025
• Est. primary completion date: October 28, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cholangitis
• Liver Cirrhosis, Biliary
• Pruritus

Intervention

Drug:
• Linerixibat
Participants will receive linerixibat.
• Placebo
Participants will receive placebo.

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Caba	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	Rosario	Santa Fe
Argentina	GSK Investigational Site	San Nicolas	Buenos Aires
Argentina	GSK Investigational Site	Santa Fe
Belgium	GSK Investigational Site	Brussels
Belgium	GSK Investigational Site	Gent
Brazil	GSK Investigational Site	Botucatu	São Paulo
Brazil	GSK Investigational Site	Brasilia	Distrito Federal
Brazil	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul
Brazil	GSK Investigational Site	Salvador	Bahia
Bulgaria	GSK Investigational Site	Plovdiv
Bulgaria	GSK Investigational Site	Sofia
Bulgaria	GSK Investigational Site	Sofia
Bulgaria	GSK Investigational Site	Sofia
Canada	GSK Investigational Site	Edmonton	Alberta
Canada	GSK Investigational Site	Toronto	Ontario
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Changchun	Jilin
China	GSK Investigational Site	Chongqing	Sichuan
China	GSK Investigational Site	Guangzhou	Guangdong
China	GSK Investigational Site	Nanchang	Jiangxi
China	GSK Investigational Site	Nanjing	Jiangsu
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Tianjin
China	GSK Investigational Site	Zhanjiang	Guangdong
Czechia	GSK Investigational Site	Ostrava
Czechia	GSK Investigational Site	Plzen
Czechia	GSK Investigational Site	Praha 4
France	GSK Investigational Site	Créteil cedex
France	GSK Investigational Site	Grenoble cedex 9
France	GSK Investigational Site	Lille cedex
France	GSK Investigational Site	Paris
Germany	GSK Investigational Site	Duesseldorf	Nordrhein-Westfalen
Germany	GSK Investigational Site	Erlangen	Bayern
Germany	GSK Investigational Site	Essen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Muenster	Nordrhein-Westfalen
Greece	GSK Investigational Site	Athens
Israel	GSK Investigational Site	Beer Sheva
Israel	GSK Investigational Site	Haifa
Israel	GSK Investigational Site	Holon
Israel	GSK Investigational Site	Jerusalem
Israel	GSK Investigational Site	Nahariya
Israel	GSK Investigational Site	Rehovot
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Modena	Emilia-Romagna
Italy	GSK Investigational Site	Monza	Lombardia
Italy	GSK Investigational Site	Napoli	Campania
Italy	GSK Investigational Site	Negrar Di Valpolicella	Veneto
Italy	GSK Investigational Site	Palermo	Sicilia
Italy	GSK Investigational Site	Roma	Lazio
Italy	GSK Investigational Site	Rozzano	Lombardia
Japan	GSK Investigational Site	Ehime
Japan	GSK Investigational Site	Fukui
Japan	GSK Investigational Site	Hiroshima
Japan	GSK Investigational Site	Hiroshima
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Ibaraki
Japan	GSK Investigational Site	Kagawa
Japan	GSK Investigational Site	Kanagawa
Japan	GSK Investigational Site	Nagano
Japan	GSK Investigational Site	Nagasaki
Japan	GSK Investigational Site	Nara
Japan	GSK Investigational Site	Shizuoka
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Mexico	GSK Investigational Site	Mexico City	Ciudad De Mexico
Mexico	GSK Investigational Site	Mexico, City	Ciudad De Mexico
Mexico	GSK Investigational Site	Monterrey	Nuevo León
Poland	GSK Investigational Site	Czestochowa
Poland	GSK Investigational Site	Katowice
Poland	GSK Investigational Site	Myslowice
Poland	GSK Investigational Site	Warszawa
Poland	GSK Investigational Site	Wroclaw
Russian Federation	GSK Investigational Site	Kemerovo
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Novosibirsk
Russian Federation	GSK Investigational Site	Samara
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Santander
Spain	GSK Investigational Site	Sevilla
Switzerland	GSK Investigational Site	Lugano
United Kingdom	GSK Investigational Site	Basingstoke
United Kingdom	GSK Investigational Site	Cambridge
United Kingdom	GSK Investigational Site	Durham
United Kingdom	GSK Investigational Site	Hull
United Kingdom	GSK Investigational Site	Liverpool
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	Newcastle upon Tyne
United Kingdom	GSK Investigational Site	Plymouth
United Kingdom	GSK Investigational Site	Reading
United Kingdom	GSK Investigational Site	Redhill	Surrey
United Kingdom	GSK Investigational Site	Southampton
United States	GSK Investigational Site	Boston	Massachusetts
United States	GSK Investigational Site	Colorado Springs	Colorado
United States	GSK Investigational Site	Columbus	Ohio
United States	GSK Investigational Site	Culver City	California
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Durham	North Carolina
United States	GSK Investigational Site	Hialeah	Florida
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Jackson	Mississippi
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	Novi	Michigan
United States	GSK Investigational Site	Omaha	Nebraska
United States	GSK Investigational Site	Philadelphia	Pennsylvania
United States	GSK Investigational Site	Sacramento	California
United States	GSK Investigational Site	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Bulgaria,  Canada,  China,  Czechia,  France,  Germany,  Greece,  Israel,  Italy,  Japan,  Mexico,  Poland,  Russian Federation,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline in Monthly Itch Scores over 24 weeks using Numerical Rating Scale (NRS)	Monthly Itch Score will be assessed using an NRS, ranging from 0 to 10, where 0 represents no itching and 10 the worst imaginable itching.	Baseline and up to 24 weeks
Secondary	Change from Baseline in Weekly Itch Score at Week 2	Weekly Itch Score will be assessed using an NRS, ranging from 0 to 10, where 0 represents no itching and 10 the worst imaginable itching.	Baseline and Week 2
Secondary	Change from Baseline in Monthly Sleep Score as measured by NRS over 24 weeks	Monthly Sleep Score will be assessed using an NRS scale, ranging from 0 to 10, where 0 represents no sleep interference and 10 is complete sleep interference.	Baseline and up to 24 weeks
Secondary	Change from Baseline in Primary Biliary Cholangitis-40 (PBC-40) domain scores at Week 24	PBC-40 questionnaire measure is comprised of 40 questions, each scored on a scale of 1 to 5 (where 1 = least impact, 5 = greatest impact) grouped into six domains.	Baseline and Week 24
Secondary	Number of participants achieving a >=2-point reduction from Baseline in the Monthly Itch Score at Week 24	Number of participants achieving a >=2-point reduction from Baseline in the Monthly Itch Score will be assessed.	Baseline and Week 24
Secondary	Number of participants achieving a >=3-point reduction from Baseline in the Monthly Itch Score at Week 24	Number of participants achieving a >=3-point reduction from Baseline in the Monthly Itch Score will be assessed.	Baseline and Week 24
Secondary	Number of participants as achieving a >=4-point reduction from Baseline in the Monthly Itch Score at Week 24	Number of participants as achieving a >=4-point reduction from Baseline in the Monthly Itch Score will be assessed.	Baseline and Week 24
Secondary	Change from Baseline in Patient's Global Impression of Severity (PGI-S) over 24 weeks	Participant-reported overall impression of itch severity will be assessed by PGI-S questionnaire using a 5-level response scale, ranging from absent to very severe.	Baseline and up to 24 weeks
Secondary	Patient's Global Impression of Change (PGI-C) scores over 24 weeks	Participant-reported change in itch severity will be assessed by PGI-C questionnaire using a 7-level response scale, ranging from very much improved to very much worse.	Up to 24 weeks
Secondary	Change from Baseline in alkaline phosphatase (ALP) at Week 24	Change from Baseline in ALP at Week 24 will be evaluated.	Baseline and Week 24
Secondary	Change from Baseline in bilirubin at Week 24	Change from Baseline in bilirubin at Week 24 will be evaluated.	Baseline and Week 24