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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04950127
Recruitment Status : Recruiting
First Posted : July 6, 2021
Last Update Posted : August 4, 2022
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

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.

Condition or disease Intervention/treatment Phase
Pruritus Drug: Linerixibat Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 230 participants
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
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)
Actual Study Start Date : August 27, 2021
Estimated Primary Completion Date : November 23, 2023
Estimated Study Completion Date : November 23, 2023


Arm Intervention/treatment
Experimental: Participants receiving linerixibat Drug: Linerixibat
Participants will receive linerixibat.

Experimental: Participants receiving linerixibat followed by placebo Drug: Linerixibat
Participants will receive linerixibat.

Drug: Placebo
Participants will receive placebo.

Placebo Comparator: Participants receiving placebo Drug: Placebo
Participants will receive placebo.

Experimental: Participants receiving placebo followed by linerixibat Drug: Linerixibat
Participants will receive linerixibat.

Drug: Placebo
Participants will receive placebo.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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:

  • Symptoms suggestive of active coronavirus disease 2019 (COVID-19) infection whilst symptoms persist or known COVID-19 positive contacts within the past 14 days should be excluded for at least 14 days from the exposure.
  • 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 actively replicating viral hepatitis B or C (HBV, HCV) 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 symptoms (e.g., atopic dermatitis, psoriasis).
  • Primary sleep disorders such as but are not limited to sleep apnea, narcolepsy, hypersomnia.
  • Current/previous diagnosis of colorectal cancer.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04950127


Contacts
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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

Locations
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Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT04950127    
Other Study ID Numbers: 212620
First Posted: July 6, 2021    Key Record Dates
Last Update Posted: August 4, 2022
Last Verified: August 2022
Individual Participant Data (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
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
Cholestasis
GLISTEN
GSK2330672
Itch
Primary biliary cholangitis
Pruritus
Additional relevant MeSH terms:
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Cholangitis
Liver Cirrhosis, Biliary
Pruritus
Skin Diseases
Skin Manifestations
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases
Cholestasis, Intrahepatic
Cholestasis
Liver Diseases
Liver Cirrhosis
Fibrosis
Pathologic Processes