Global Linerixibat Itch STudy of Efficacy and Safety iN PBC (GLISTEN)

Phase 1

• Conditions: Moderate to severe Cholestatic pruritus with primary biliary cholangitis (PBC).; MedDRA version: 24.1Level: PTClassification code 10064190Term: Cholestatic pruritusSystem Organ Class: 10040785 - Skin and subcutaneous tissue disorders; MedDRA version: 21.0Level: PTClassification code 10080429Term: Primary biliary cholangitisSystem Organ Class: 10019805 - Hepatobiliary disorders; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: EUCTR2021-000007-21-BE
• Lead Sponsor: GlaxoSmithKline Research & Development Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-06-02
• Last Update Posted: 3 June 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 230

Inclusion Criteria

Participants are eligible to be included in the study only if all of the following criteria apply:
Sex and Age
1. Male and female participants must be between 18 to 80 years of age inclusive, at the time of signing the informed consent.
Note: if country/site age requirements for consent differ, the more stringent (e.g., higher age) restriction will be required for that country/site.
Type of Participant and Disease Characteristics
2. Participants who have proven PBC, as demonstrated by historically having at least 2 of the following:
• Documented history of sustained increased ALP levels greater than ULN first recognized at least 6 months prior to the Screening Visit (Note: Sustained ALP elevations at the time of Screening is not required, recognizing that the ALP may have decreased after initiation of UDCA therapy).
• Documented positive anti-mitochondrial antibody (AMA) titer (>1:40 titer on immunofluorescence or M2 positive by enzyme linked immunosorbent assay [ELISA]) or PBC-specific antinuclear antibodies (antinuclear dot and/or nuclear rim positive).
• Liver biopsy (documented at any time in the past) consistent with PBC.
3. Participants who, during the Screening period, record their daily itch score by entering at least 40 of the 56 required itch entries, with an entry on at least 4 days in each week, during the 4-week period immediately preceding Randomization at Day 1 and have a Monthly Itch Score of =4 (i.e., at least 1 of the 4 weekly Itch Scores must be =4), and no Weekly Itch Score can be <3 for any other week.
Contraceptive/Barrier Requirements
4. Contraceptive/Barrier Requirements (applicable for female participants only): A female participant is eligible to participate if she is not pregnant or breastfeeding, and
one of the following conditions applies:
o Is a woman of non-childbearing potential (WONCBP)
OR
o Is a woman of childbearing potential (WOCBP) and using an acceptable contraceptive method as described in Section 10.4 during the study intervention period (at a minimum until 4 weeks after the last dose of study intervention).
The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated in relationship to the first dose of study intervention.
• A WOCBP must have a negative highly sensitive urine pregnancy test (or serum as required by local regulations) within 7 days before the first dose of study intervention, see Section 8.2.5 Pregnancy Testing.
Note: If a serum pregnancy test is required by local regulations, sample collection must be arranged before Visit 3 to ensure the result confirming eligibility can be available before randomization.
• Additional requirements for pregnancy testing during and after study intervention are located in Section 8.2.5.
• The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy
Note: Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Full requirements for pregnancy testing during and after study intervention are located in Section 10.4 Appendix 4.
Informed Consent
5. Capable of giving signed informed consent as described in Section 10.1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Are the trial subjects u

Exclusion Criteria

Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
1. Total bilirubin >2.0 x ULN using the average of two baseline measures. Note: Total bilirubin > 2x ULN but < 3x ULN is acceptable if bilirubin is fractionated and direct bilirubin is < 35%
2. Screening ALT > 6x ULN in a single baseline measure or ALT > 5x ULN using the average of two baseline measures.
3. Participants with abnormal liver biochemistry (ALT, aspartate aminotransferase [AST], ALP, or total bilirubin) during the Screening period (at Visit 1 or Visit 2) and the variance between these two samples for the abnormal parameter is >40%.
Note: Variance will be calculated as the absolute value of [(Sample 1- Sample 2)/average of Sample 1 and Sample 2) x100]. Sample 1 and Sample 2 must be collected at least 4 weeks apart. If variance of >40% is seen between Visit 1 and 2 samples, an additional sample may be taken and the variance between the additional sample (third sample) and the Screening (Visit 1) sample must be = 40%
4. Screening estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2 based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
5. History or presence of hepatic decompensation (e.g., variceal bleeding, hepatic encephalopathy or ascites).
6. Presence of viral hepatitis B (HBsAg positive) or C (anti-HCV positive and RNA detected) infection, primary sclerosing cholangitis (PSC), alcoholic liver disease and/or confirmed hepatocellular carcinoma or biliary cancer.
7. Infection with human immunodeficiency virus (HIV)
8. Current clinically significant diarrhea in the Investigator’s medical opinion.
9. Active inflammatory ileal disease according to Investigator´s clinical judgment.
10. Current symptomatic cholelithiasis or cholecystitis. (Participants with history of cholecystectomy =12 weeks before screening may be eligible for enrolment at the discretion of the investigator.)
11. Current diagnosis of primary skin disorders with itch as a characteristic feature (e.g., atopic dermatitis, psoriasis).
12. Primary sleep disorders such as but are not limited to sleep apnea, narcolepsy, hypersomnia
13. Any current malignancies (including hematologic and solid malignancies).
14. History of bariatric surgery with ileal bypass at any time, or any bariatric surgery performed in the past 3 years
15. Any current uncontrolled psychiatric condition
16. Any current medical condition (e.g. senility or dementia), which may affect the participant’s ability to comply with the protocol specified procedures.
Prior/Concomitant Therapy
17. Initiation, discontinuation or change in dose of UDCA in the 8 weeks prior to Screening. (Participants may join the study on stable doses of UDCA, but no initiation, discontinuation, or change in dose is permitted until completion of the
Treatment Periods.)
18. Use of obeticholic acid: within 8 weeks prior to Screening. (Participants may not initiate or restart during the study, please see Section 6.8.2)
19. Initiation, discontinuation or change in dose of fibrates at any time during the 8 weeks prior to Screening. (Participants may join the study on stable doses of these medications, but no initiation, discontinuation, or change in dose is permitted until completion of the Treatment Periods.)
20. 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, pre

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified