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: 21.1Level: 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-IT
• Lead Sponsor: GLAXOSMITHKLINE RESEARCH AND DEVELOPMENT

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-08-17
• Last Update Posted: 24 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• 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 Mean Worst Daily Itch Scores must be =4), and no Mean Worst Daily 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 not a woman of non-childbearing potential
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.
• 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 under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 175
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Numbe

Exclusion Criteria

1. Participants with symptoms suggestive of active COVID-19 infection (i.e. fever,cough, loss of taste or smell etc.) are excluded whilst symptoms persist.
2. Total bilirubin >2.0 x ULN using the average of two baseline measures.
3. Screening ALT > 6x ULN in a single baseline measure or ALT > 5x ULN using the average of two baseline measures.
4. 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%.
5. Screening estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2 based on CKD-EPI equation.
6. History or presence of hepatic decompensation (e.g., variceal bleeding, hepatic encephalopathy or ascites).
7. 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.
8. Infection with human immunodeficiency virus (HIV)
9. Current clinically significant diarrhea in the Investigator's medical opinion.
10. Active inflammatory ileal disease according to Investigator´s clinical judgment.
11. Current symptomatic cholelithiasis or cholecystitis.
12. Current diagnosis of primary skin disorders with itch symptoms (e.g.,atopic dermatitis, psoriasis).
13. Primary sleep disorders such as but are not limited to sleep apnea,narcoleptsy,hypersomnia
14. Any current malignancies (including hematologic and solid malignancies).
15. Current/previous diagnosis of colorectal cancer.
16. History of bariatric surgery with ileal bypass at any time, or any bariatric surgery performed in the past 3 years
17. Any current uncontrolled psychiatric condition
18. 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
19. Initiation, discontinuation or change in dose of UDCA in the 8 weeks prior to Screening
20. Use of obeticholic acid: within 8 weeks prior to Screening
21. Initiation, discontinuation or change in dose of bezafibrate or fenofibrate at any time during the 8 weeks prior to Screening.
22. 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 SSRIs.
23. Initiation, discontinuation or change in dose of opioids, regardless of indication, in the 8 weeks prior to Screening.
24. Initiation, discontinuation or change in dose of colchicine, methotrexate ,azathioprine, or systemic corticosteroids in the 8 weeks prior to Screening
25. Initiation, discontinuation, or change in dose of antihistamines used for the treatment of itching the 8 weeks prior to Screening.

Study & Design

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