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

• ClinicalTrials.gov Identifier: NCT04950127
• Recruitment Status: Recruiting
• First Posted: July 6, 2021
• Last Update Posted: April 3, 2024
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Tracking Information

• First Submitted Date: June 25, 2021
• First Posted Date: July 6, 2021
• Last Update Posted Date: April 3, 2024
• Actual Study Start Date: August 27, 2021
• Estimated Primary Completion Date: October 30, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 25, 2021)

Change from Baseline in Monthly Itch Scores over 24 weeks using Numerical Rating Scale (NRS) [ Time Frame: Baseline and up to 24 weeks ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 13, 2024)

• Change from Baseline in Weekly Itch Score at Week 2 [ Time Frame: Baseline and 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.
• Change from Baseline in Monthly Sleep Score as measured by NRS over 24 weeks [ Time Frame: Baseline and up to 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.
• Change from Baseline in Primary Biliary Cholangitis-40 (PBC-40) domain scores at Week 24 [ Time Frame: Baseline and 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.
• Number of participants achieving a >=2-point reduction from Baseline in the Monthly Itch Score at Week 24 [ Time Frame: Baseline and Week 24 ]
  Number of participants achieving a >=2-point reduction from Baseline in the Monthly Itch Score will be assessed.
• Number of participants achieving a >=3-point reduction from Baseline in the Monthly Itch Score at Week 24 [ Time Frame: Baseline and Week 24 ]
  Number of participants achieving a >=3-point reduction from Baseline in the Monthly Itch Score will be assessed.
• Number of participants as achieving a >=4-point reduction from Baseline in the Monthly Itch Score at Week 24 [ Time Frame: Baseline and Week 24 ]
  Number of participants as achieving a >=4-point reduction from Baseline in the Monthly Itch Score will be assessed.
• Change from Baseline in Patient's Global Impression of Severity (PGI-S) over 24 weeks [ Time Frame: Baseline and up to 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.
• Patient's Global Impression of Change (PGI-C) scores over 24 weeks [ Time Frame: Up to 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.
• Change from Baseline in alkaline phosphatase (ALP) at Week 24 [ Time Frame: Baseline and Week 24 ]
  Change from Baseline in ALP at Week 24 will be evaluated.
• Change from Baseline in bilirubin at Week 24 [ Time Frame: Baseline and Week 24 ]
  Change from Baseline in bilirubin at Week 24 will be evaluated.

Original Secondary Outcome Measures (submitted: June 25, 2021)

• Change from Baseline in Mean Worst Daily Itch score at Week 2 [ Time Frame: Baseline and Week 2 ]
  Mean Worst Daily Itch score will be assessed using an NRS, ranging from 0 to 10, where 0 represents no itching and 10 the worst imaginable itching.
• Change from Baseline in Monthly Sleep Score as measured by NRS over 24 weeks [ Time Frame: Baseline and up to 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.
• Change from Baseline in Primary Biliary Cholangitis-40 (PBC-40) domain scores at Week 24 [ Time Frame: Baseline and 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.
• Number of participants achieving a >=2-point reduction from Baseline in the Monthly Itch Score at Week 24 [ Time Frame: Baseline and Week 24 ]
  Number of participants achieving a >=2-point reduction from Baseline in the Monthly Itch Score will be assessed.
• Number of participants achieving a >=3-point reduction from Baseline in the Monthly Itch Score at Week 24 [ Time Frame: Baseline and Week 24 ]
  Number of participants achieving a >=3-point reduction from Baseline in the Monthly Itch Score will be assessed.
• Number of participants as achieving a >=4-point reduction from Baseline in the Monthly Itch Score at Week 24 [ Time Frame: Baseline and Week 24 ]
  Number of participants as achieving a >=4-point reduction from Baseline in the Monthly Itch Score will be assessed.
• Change from Baseline in Patient's Global Impression of Severity (PGI-S) over 24 weeks [ Time Frame: Baseline and up to 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.
• Patient's Global Impression of Change (PGI-C) scores over 24 weeks [ Time Frame: Up to 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.
• Change from Baseline in alkaline phosphatase (ALP) at Week 24 [ Time Frame: Baseline and Week 24 ]
  Change from Baseline in ALP at Week 24 will be evaluated.
• Change from Baseline in bilirubin at Week 24 [ Time Frame: Baseline and Week 24 ]
  Change from Baseline in bilirubin at Week 24 will be evaluated.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Global Linerixibat Itch Study of Efficacy and Safety in Primary Biliary Cholangitis (PBC) (GLISTEN)
• 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)
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

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

Masking: Double (Participant, Investigator)
Masking Description:

Participants and investigator will be blinded to the study treatment.

Primary Purpose: Treatment

• Condition: Pruritus

Intervention

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

Study Arms

• Experimental: Participants receiving linerixibat
  Intervention: Drug: Linerixibat
• Experimental: Participants receiving linerixibat followed by placebo
  Interventions:

  • Drug: Linerixibat
  • Drug: Placebo
• Placebo Comparator: Participants receiving placebo
  Intervention: Drug: Placebo
• Experimental: Participants receiving placebo followed by linerixibat
  Interventions:

  • Drug: Linerixibat
  • Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 25, 2021): 230
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 8, 2025
• Estimated Primary Completion Date: October 30, 2024 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: US GSK Clinical Trials Call Center; 877-379-3718; GSKClinicalSupportHD@gsk.com

Contact: EU GSK Clinical Trials Call Center; +44 (0) 20 89904466; GSKClinicalSupportHD@gsk.com

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

Administrative Information

• NCT Number: NCT04950127
• Other Study ID Numbers: 212620
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (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.
• URL: http://clinicalstudydatarequest.com

• Current Responsible Party: GlaxoSmithKline
• Original Responsible Party: Same as current
• Current Study Sponsor: GlaxoSmithKline
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

• PRS Account: GlaxoSmithKline
• Verification Date: April 2024