Linerixibat Long-term Safety, and Tolerability Study

Cholestasis Clinical Trial

— LLSAT  

Official title:

Long-term Safety and Tolerability Study of Linerixibat for the Treatment of Cholestatic Pruritus in Participants With Primary Biliary Cholangitis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04167358
• Other study ID #: 212358
• Secondary ID: 2019-003158-10
• Status: Recruiting
• Phase: Phase 3
• Start date: July 14, 2020
• Est. completion date: February 2, 2027

Study information

• Verified date: October 2023
• Source: GlaxoSmithKline
• Contact: US GSK Clinical Trials Call Center
• Phone: 877-379-3718
• Email: GSKClinicalSupportHD[@]gsk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 305
• Est. completion date: February 2, 2027
• Est. primary completion date: February 2, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cholestasis
• Liver Cirrhosis, Biliary

Intervention

Drug:
• Linerixibat
All participants will receive linerixibat.

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	Goiás
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	Montréal	Quebec
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	Xi'an
China	GSK Investigational Site	Zhanjiang	Guangdong
China	GSK Investigational Site	Zhengzhou
Czechia	GSK Investigational Site	Ostrava
Czechia	GSK Investigational Site	Plzen
Czechia	GSK Investigational Site	Praha 4
France	GSK Investigational Site	Lille cedex
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	Haifa
Israel	GSK Investigational Site	Holon
Israel	GSK Investigational Site	Jerusalem
Israel	GSK Investigational Site	Nahariya
Israel	GSK Investigational Site	Ramat Gan
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	Negrar Di Valpolicella	Veneto
Italy	GSK Investigational Site	Padova	Veneto
Italy	GSK Investigational Site	Roma	Lazio
Italy	GSK Investigational Site	Rozzano	Lombardia
Japan	GSK Investigational Site	Chiba
Japan	GSK Investigational Site	Ehime
Japan	GSK Investigational Site	Fukui
Japan	GSK Investigational Site	Gunma
Japan	GSK Investigational Site	Hiroshima
Japan	GSK Investigational Site	Hiroshima
Japan	GSK Investigational Site	Hokkaido
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	Osaka
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Shizuoka
Japan	GSK Investigational Site	Tokyo
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	Samara
Spain	GSK Investigational Site	Valencia
Switzerland	GSK Investigational Site	Lugano
United Kingdom	GSK Investigational Site	Basingstoke
United Kingdom	GSK Investigational Site	Cambridge
United Kingdom	GSK Investigational Site	Glasgow
United Kingdom	GSK Investigational Site	Hull
United Kingdom	GSK Investigational Site	Liverpool
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	Newcastle Upon Tyne
United Kingdom	GSK Investigational Site	Nottingham
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	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	Durham	North Carolina
United States	GSK Investigational Site	Hialeah	Florida
United States	GSK Investigational Site	Los Angeles	California
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	Sacramento	California
United States	GSK Investigational Site	Seattle	Washington

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	Number of participants with non-serious adverse events (AEs) and Serious AEs (SAEs)	AEs and SAEs will be collected.	Up to 66 months
Primary	Number of participants with Severe AEs	AEs and SAEs will be collected.	Up to 66 months
Secondary	Change in domain scores of the PBC-40 over time	The PBC-40 is a participant-derived, disease specific health-related quality of life (QoL) measure with data to support its validity in PBC. The PBC-40 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 (symptoms, itch, fatigue, cognition, social, and emotional).	Baseline and up to 65 months
Secondary	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)	The EQ-5D-3L is a standardized instrument developed by the EuroQol Group as a measure of health-related quality of life that can be used in a wide range of health conditions and treatments. The EQ-5D consists of a descriptive system and the EQ Visual Analogue Scale (VAS). The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: 1=no problems, 2=some problems, and 3=extreme problems.	Baseline and up to 65 months
Secondary	Change in self-rated health by EQ VAS scores over time (Group 1 only)	The EQ-5D-3L is a standardized instrument developed by the EuroQol Group as a measure of health-related quality of life that can be used in a wide range of health conditions and treatments. The EQ-5D consists of a descriptive system and the EQ VAS. The EQ VAS records self-rated health on a vertical visual analogue scale where the endpoints are labelled 'Best imaginable health state' and 'Worst imaginable health state'.	Baseline and up to 65 months
Secondary	Change in the Beck Depression Inventory (BDI-II) scores over time	The BDI-II is a 21-item questionnaire used to assess the intensity of depression in clinical and normal participants. Each item is scored from 0 (Normal) to 3 (Severe). The total score on the BDI-II ranges from 0-63, with higher scores reflecting higher levels of depression.	Baseline and up to 65 months
Secondary	Number of participants with clinically significant changes in hematology, biochemistry (including lipid and liver parameters), and coagulation parameters	Blood samples will be collected for the analysis of hematology, biochemistry (including lipid and liver parameters) and coagulation parameters.	Baseline and up to 65 months
Secondary	Percentage of responders at Week 24 and Week 52 of continuous treatment (Group 2 only)	Monthly Itch Score (MIS) will be assessed using an numerical rating scale (NRS), ranging from 0 to 10, where 0 represents no itching and 10 the worst imaginable itching. Response thresholds of greater than or equal to (>=) 2, >=3, and >=4-point reduction in MIS will be assessed.	Week 24 and Week 52 of continuous treatment
Secondary	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)	The MIS will be assessed using an NRS, ranging from 0 to 10, where 0 represents no itching and 10 the worst imaginable itching. Maintenance of efficacy occurs when a participant is a responder (>=2, >=3, and >=4-point reduction in MIS) at Week 24 of continuous treatment and is also a responder at Week 52 of continuous treatment.	Week 52 of continuous treatment
Secondary	Change from Baseline Monthly Sleep Score (MSS) (Group 2 only)	The MSS will be assessed using an NRS, ranging from 0 to 10, where 0 represents no sleep interference and 10 is complete sleep interference. This will be assessed at Week 52 of continuous treatment.	Baseline and up to Week 52 of continuous treatment
Secondary	Change from Baseline in Monthly Fatigue Score (MFS)(Group 2 only)	The MFS will be assessed using an NRS, ranging from 0 to 10, where 0 represents no fatigue and 10 the worst possible fatigue. This will be assessed at Week 52 of continuous treatment.	Baseline and up to Week 52 of continuous treatment