Linerixibat Long-term Safety, and Tolerability Study

NCT04167358 | Active Not Recruiting Phase 3 FDA Drug

• 2 other identifiers: 2123582019-003158-10
• Study Type: interventional
• Target: 242
• Locations: 17 countries
• Sites: 89

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.

Conditions

Cholestasis

Keywords

Linerixibat; Cholestasis; Cholestatic pruritus; Primary biliary cholangitis; LLSAT

Outcome Measures

Primary Outcomes (2)

• Number of participants with non-serious adverse events (AEs) and Serious AEs (SAEs)

  AEs and SAEs will be collected.

  Up to 66 months

• Number of participants with Severe AEs

  AEs and SAEs will be collected.

  Up to 66 months

Secondary Outcomes (9)

• Change in domain scores of the PBC-40 over time

  Baseline and up to 65 months

• 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)

  Baseline and up to 65 months

• Change in self-rated health by EQ VAS scores over time (Group 1 only)

  Baseline and up to 65 months

• Change in the Beck Depression Inventory (BDI-II) scores over time

  Baseline and up to 65 months

• Number of participants with clinically significant changes in hematology, biochemistry (including lipid and liver parameters), and coagulation parameters

  Baseline and up to 65 months

Study Arms (1)

Participants receiving linerixibat

EXPERIMENTAL

Participants who previously participated in the Phase 2 studies (BAT117213 and 201000 GLIMMER \[Group 1\]) and Phase 3 study (212620 GLISTEN \[Group 2\]), will receive linerixibat.

Drug: Linerixibat

Interventions

Linerixibat DRUG

All participants will receive linerixibat.

Participants receiving linerixibat

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (89)

GSK Investigational Site

Davis, California, 95817, United States

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GSK Investigational Site

West Hollywood, California, 90048, United States

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Miami, Florida, 33136, United States

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Detroit, Michigan, 48377, United States

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New York, New York, 10016, United States

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Durham, North Carolina, 27710, United States

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Morrisville, North Carolina, 27560, United States

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Philadelphia, Pennsylvania, 19104, United States

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Dallas, Texas, 75390, United States

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Houston, Texas, 77030, United States

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Seattle, Washington, 98105, United States

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Buenos Aires, C1061AAS, Argentina

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Capital Federal, C1181ACI, Argentina

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Ciudad AutOnoma de Buenos Aire, 1118, Argentina

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Ciudad Autonoma de Bueno, C1056ABI, Argentina

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Rosario, S2002KDT, Argentina

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Santa Fe, 3000, Argentina

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Porto Alegre, Rio Grande do Sul, 90035003, Brazil

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Botucatu, 18618686, Brazil

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Brasília, 70335-900, Brazil

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Salvador, 40110-160, Brazil

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Sofia, 1618, Bulgaria

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Edmonton, Alberta, T6G 2X8, Canada

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Toronto, Ontario, M5G 2C4, Canada

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Beijing, 100032, China

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Beijing, 100069, China

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Changchun, 130021, China

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Chongqing, 400042, China

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Guangzhou, 510630, China

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Nanchang, 330006, China

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Nanjing, 210003, China

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Shanghai, 200127, China

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Tianjin, 300000, China

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Pilsen, 30100, Czechia

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Prague, 140 21, Czechia

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Lille, 59037, France

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Erlangen, 91054, Germany

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Münster, 48149, Germany

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Haifa, 34362, Israel

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Holon, 58100, Israel

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Jerusalem, 91120, Israel

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Naples, 80131, Italy

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Negrar Verona, 37024, Italy

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Palermo, 90127, Italy

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Roma, 00168, Italy

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Chiba, 270-1694, Japan

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Ehime, 791-0295, Japan

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Fukui, 918-8503, Japan

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Gunma, 371-8511, Japan

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Hiroshima, 730-8619, Japan

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Hiroshima, 734-8551, Japan

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Hokkaido, 006-8555, Japan

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Kagawa, 760-8557, Japan

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Kanagawa, 259-1143, Japan

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Nagano, 390-8621, Japan

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Nagasaki, 856-8562, Japan

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Nara, 634-8522, Japan

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Osaka, 545-8586, Japan

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GSK Investigational Site

Osaka, 591-8025, Japan

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Shizuoka, 431-3192, Japan

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Tokyo, 113-8603, Japan

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Tokyo, 162-8655, Japan

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Tokyo, 173-8606, Japan

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GSK Investigational Site

Tokyo, 181-8611, Japan

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Mexico City, 06700, Mexico

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Mexico City, 14080, Mexico

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Monterrey, 64020, Mexico

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Częstochowa, 42-217, Poland

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Katowice, 40-659, Poland

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Mysłowice, 41-400, Poland

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Warsaw, 03-712, Poland

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Wroclaw, 51-162, Poland

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Kemerovo, 650000, Russia

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Moscow, 119121, Russia

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GSK Investigational Site

Samara, 443063, Russia

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GSK Investigational Site

Barcelona, 08036, Spain

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GSK Investigational Site

Madrid, 28007, Spain

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GSK Investigational Site

Madrid, 28041, Spain

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GSK Investigational Site

Seville, 41013, Spain

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GSK Investigational Site

Valencia, 46026, Spain

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GSK Investigational Site

Basingstoke, RG24 9NA, United Kingdom

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Glasgow, G31 2ER, United Kingdom

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London, NW3 2QG, United Kingdom

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Newcastle upon Tyne, NE4 5PL, United Kingdom

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Nottingham, NG7 2UH, United Kingdom

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Plymouth, PL6 8DH, United Kingdom

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GSK Investigational Site

Reading Berkshire, RG1 5AN, United Kingdom

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GSK Investigational Site

Southampton, SO16 6YD, United Kingdom

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GSK Investigational Site

Surrey, RH1 5RH, United Kingdom

Location

MeSH Terms

Conditions

Cholestasis; Liver Cirrhosis, Biliary

Condition Hierarchy (Ancestors)

Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Cholestasis, Intrahepatic; Liver Diseases; Liver Cirrhosis; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Masking Details: This is an open label non-comparator study.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Model Details: This is a non-comparator single group study.

Study Record Dates

• First Submitted: November 15, 2019
• First Posted: November 18, 2019
• Study Start: July 14, 2020
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: February 20, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

IT (4); CA (2); RU (3); PL (5); AR (6); GB (9); CN (9); ME (3); US (11); JP (19); ES (5); DE (2); BU (1); FR (1); IL (3); BR (4); CZ (2)