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Phase 3 N=238 Randomized Double-blind Treatment

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

Pruritus

Enrolled (actual)
238
Serious AEs
4.6%
Results posted
Jul 2025
Primary outcome: Primary: Part A: Mean Change From Baseline in Monthly Itch Scores Over 24 Weeks Using Numerical Rating Scale (NRS) — -2.86; -2.15 Scores on a scale — p=0.001

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
Linerixibat (Drug); Placebo (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
GlaxoSmithKline
Primary completion
Oct 2024

Outcome Measures

OutcomeResultp-value
PRIMARY
Part A: Mean Change From Baseline in Monthly Itch Scores Over 24 Weeks Using Numerical Rating Scale (NRS)
-2.86; -2.15 0.001 sig
SECONDARY
Part A: Mean Change From Baseline in Weekly Itch Score at Week 2 Using NRS
-1.78; -1.07 <0.001 sig
SECONDARY
Part A: Mean Change From Baseline in Monthly Sleep Score Over 24 Weeks Using NRS
-2.77; -2.24 0.024 sig
SECONDARY
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
68.0; 64.0 0.539
SECONDARY
Part A: Percentage of Responders Achieving >=3-point Reduction From Baseline in the Monthly Itch Score at Week 24
56.0; 43.0 0.043 sig
SECONDARY
Part A: Percentage of Responders as Achieving a >=4-point Reduction From Baseline in the Monthly Itch Score at Week 24
41.0; 29.0 0.058
SECONDARY
Part A: Mean Change From Baseline in Primary Biliary Cholangitis-40 (PBC-40) Domain Scores at Week 24
-0.71; -1.47; -1.07; -1.34; -2.94; -4.54 0.176
SECONDARY
Part A: Mean Change From Baseline in Patient's Global Impression of Severity (PGI-S) Over 24 Weeks
-1.22; -0.84 <0.001 sig
SECONDARY
Part A: Patient's Global Impression of Change (PGI-C) Scores Over 24 Weeks
1.97; 2.46 <0.001 sig
SECONDARY
Part A: Mean Change From Baseline in Alkaline Phosphatase (ALP) at Week 24
10.61; -8.03
SECONDARY
Part A: Mean Change From Baseline in Bilirubin at Week 24
1.77; -0.31

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.
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT04950127). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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