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

NCT04950127 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: 212620
• Study Type: interventional
• Target: 238
• Locations: 19 countries
• Sites: 114

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.

Conditions

Pruritus

Keywords

Cholestasis; GLISTEN; GSK2330672; Itch; Primary biliary cholangitis; Pruritus

Outcome Measures

Primary Outcomes (1)

• Part A: Mean Change From Baseline in Monthly Itch Scores Over 24 Weeks Using Numerical Rating Scale (NRS)

  Itch Scores were assessed using a NRS twice daily, ranging from 0 to 10, where 0 represents no itching and 10 the worst imaginable itching. The worst daily itch score was defined as the worst of the two scores recorded daily. The weekly itch score was defined as the average of the worst daily itch scores in one week. The monthly itch score was defined as the worst weekly itch score for the month (4 weeks). Higher monthly itch scores indicate worse itching. Baseline is the worst weekly itch score in the 28 days prior to randomization (Day 1). Change from Baseline is defined as the post dose value minus baseline value. Least-squares (LS) means and the corresponding 95% confidence intervals are reported by taking average of LS means of change from baseline in monthly itch scores obtained over 24 weeks using equal weighting for all time points. Analyzed using Mixed Model Repeated Measures (MMRM) method.

  Baseline and up to Week 24

Secondary Outcomes (10)

• Part A: Mean Change From Baseline in Weekly Itch Score at Week 2 Using NRS

  Baseline and at Week 2

• Part A: Mean Change From Baseline in Monthly Sleep Score Over 24 Weeks Using NRS

  Baseline up to Week 24

• Part A: Percentage of Responders Defined as Achieving More Than or Equal to (>=) 2-point Reduction From Baseline in the Monthly Itch Score at Week 24

  At Week 24

• Part A: Percentage of Responders Achieving >=3-point Reduction From Baseline in the Monthly Itch Score at Week 24

  At Week 24

• Part A: Percentage of Responders as Achieving a >=4-point Reduction From Baseline in the Monthly Itch Score at Week 24

  At Week 24

Study Arms (6)

Part A: Linerixibat 40 milligrams (mg)

EXPERIMENTAL

Participants were randomized to receive linerixibat 40 mg tablet orally twice a day (BID) in Part A (up to Week 24).

Drug: Linerixibat

Part A: Placebo

EXPERIMENTAL

Participants were randomized to receive Placebo orally twice a day (BID) in Part A (up to Week 24).

Drug: Linerixibat; Drug: Placebo

Part B: Placebo in Part A and Part B

PLACEBO COMPARATOR

Participants who were randomized to receive Placebo (up to Week 24) orally twice a day (BID) in Part A, continued to receive Placebo (from Week 24 to Week 32) orally twice a day (BID) in Part B.

Drug: Placebo

Part B: Placebo in Part A and Linerixibat 40 mg in Part B

EXPERIMENTAL

Participants who were randomized to receive Placebo (up to Week 24) orally twice a day (BID) in Part A, switched to receive linerixibat 40 mg tablet orally twice a day (BID) (from Week 24 to Week 32) in Part B.

Drug: Linerixibat; Drug: Placebo

Part B: Linerixibat 40 mg in Part A and Placebo in Part B

EXPERIMENTAL

Participants who were randomized to receive linerixibat 40 mg tablet orally BID (up to Week 24) in Part A, switched to receive Placebo (from Week 24 to Week 32) orally twice a day (BID) in Part B.

Drug: Linerixibat; Drug: Placebo

Part B: Linerixibat 40 mg in Part A and Part B

EXPERIMENTAL

Participants who were randomized to receive linerixibat 40 mg tablet orally twice a day (BID) (up to Week 24) in Part A, continued to receive linerixibat 40 mg twice a day (BID) (from Week 24 to Week 32) in Part B.

Drug: Linerixibat

Interventions

Linerixibat DRUG

Participants will receive linerixibat.

Part A: Linerixibat 40 milligrams (mg); Part A: Placebo; Part B: Linerixibat 40 mg in Part A and Part B; Part B: Linerixibat 40 mg in Part A and Placebo in Part B; Part B: Placebo in Part A and Linerixibat 40 mg in Part B

Placebo DRUG

Participants will receive placebo.

Part A: Placebo; Part B: Linerixibat 40 mg in Part A and Placebo in Part B; Part B: Placebo in Part A and Linerixibat 40 mg in Part B; Part B: Placebo in Part A and Part B

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 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (114)

GSK Investigational Site

Davis, California, 95817, United States

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Los Angeles, California, 90048, United States

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San Francisco, California, 94143, United States

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Colorado Springs, Colorado, 80907, United States

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Hialeah, Florida, 33012, United States

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Miami, Florida, 33032, United States

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Miami, Florida, 33136, United States

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Detroit, Michigan, 48377, United States

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Jackson, Mississippi, 39216, United States

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Omaha, Nebraska, 68198-2000, 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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Columbus, Ohio, 43210, United States

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Philadelphia, Pennsylvania, 19104, United States

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Dallas, Texas, 75203, United States

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Dallas, Texas, 75390, United States

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Houston, Texas, 77030, 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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San Nicolás, B2900DMH, Argentina

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Santa Fe, 3000, Argentina

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Ghent, 9000, Belgium

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Porto Alegre, Rio Grande do Sul, 90035003, Brazil

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Botucatu, 18618686, Brazil

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Brasília, 70.335-900, Brazil

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Salvador, 40110-160, Brazil

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Plovdiv, 4004, Bulgaria

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Sofia, 1618, Bulgaria

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Sofia, 1797, 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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Zhanjiang, 524000, China

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Ostrava, 708 52, Czechia

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Pilsen, 30100, Czechia

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Prague, 140 21, Czechia

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Créteil, 94010, France

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Grenoble, 38043, France

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Lille, 59037, France

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Paris, 75012, France

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Erlangen, 91054, Germany

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Essen, 45147, Germany

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Münster, 48149, Germany

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Athens, 115 27, Greece

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Beersheba, 84101, Israel

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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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Nahariya, 22100, Israel

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Rehovot, 76100, Israel

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Milan, 20142, Italy

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Modena, 41126, Italy

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Monza, 20900, Italy

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Napoli, 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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Rozzano MI, 20089, Italy

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Ehime, 791-0295, Japan

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Fukui, 918-8503, 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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Ibaraki, 300-0028, 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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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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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, 111123, Russia

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Moscow, 119121, Russia

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Novosibirsk, 630005, Russia

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Samara, 443063, Russia

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Barcelona, 08036, Spain

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Madrid, 28007, Spain

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Madrid, 28041, Spain

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Seville, 41013, Spain

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Basingstoke, RG24 9AA, United Kingdom

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Cambridge, CB2 0QQ, United Kingdom

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Durham, DH1 5TW, United Kingdom

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Hull, HU3 2JZ, United Kingdom

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Liverpool, L9 7AL, United Kingdom

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London, E1 1FR, United Kingdom

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London, NW3 2QG, United Kingdom

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Newcastle upon Tyne, NE4 6BE, United Kingdom

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Plymouth, PL6 8DH, United Kingdom

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Reading Berkshire, RG1 5AN, United Kingdom

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Southampton, SO16 6YD, United Kingdom

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Surrey, RH1 5RH, United Kingdom

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Related Publications (2)

• Hirschfield GM, Bowlus CL, Jones DEJ, Kremer AE, Mayo MJ, Tanaka A, Andreone P, Jia J, Jin Q, Macias-Rodriguez RU, Cobitz AR, Currie BM, Gorey C, Lazic I, Podmore D, Ribeiro A, Shannon JB, Swift B, McLaughlin MM, Levy C; GLISTEN Study Group. Linerixibat in patients with primary biliary cholangitis and cholestatic pruritus (GLISTEN): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial. Lancet Gastroenterol Hepatol. 2026 Jan;11(1):22-33. doi: 10.1016/S2468-1253(25)00192-X. Epub 2025 Oct 28.

  PMID: 41173016 DERIVED

• Carreno F, Karatza E, Mehta R, Collins J, Austin D, Swift B. Population Dose-Response-Time Analysis of Itch Reduction and Patient-Reported Tolerability Supports Phase III Dose Selection for Linerixibat. Clin Pharmacol Ther. 2024 Feb;115(2):288-298. doi: 10.1002/cpt.3103. Epub 2023 Dec 3.

  PMID: 37953500 DERIVED

MeSH Terms

Conditions

Pruritus; Cholestasis; Liver Cirrhosis, Biliary

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Participants and investigator will be blinded to the study treatment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Model Details: Participants will be randomized to receive linerixibat and/or placebo during the study.

Study Record Dates

• First Submitted: June 25, 2021
• First Posted: July 6, 2021
• Study Start: August 27, 2021
• Primary Completion: October 28, 2024
• Study Completion: December 20, 2024
• Last Updated: July 22, 2025
• Results First Posted: July 22, 2025

Record last verified: 2025-07

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, a 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

IL (6); JP (15); GR (1); BE (1); CA (2); GB (12); ES (4); AR (7); IT (8); ME (3); BR (4); BU (3); CZ (3); DE (3); US (18); CN (10); FR (4); RU (5); PL (5)