Ph 3a, linerixibat, Long term safety and tolerability study in pts with PBC

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Glaxosmithkline Research & Development Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

3 Jul 2020 → ongoing

Decision date (initial)

2023-08-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

GSK Pharma R&D

External identifiers

EU CT number

2023-503465-33-00

EudraCT number

2019-003158-10

ClinicalTrials.gov

NCT04124965

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

"To evaluate the safety and tolerability of long-term linerixibat treatment in participants with cholestatic pruritus in PBC "

Secondary objectives 4

1. "To characterize the effects of long-term linerixibat treatment on disease burden and health related QOL in participants with cholestatic pruritus in PBC "
2. "To characterize the effects of long-term linerixibat treatment in participants with cholestatic pruritus in PBC "
3. "To evaluate the maintenance of efficacy of linerixibat on itch over 52 weeks"
4. To evaluate the effect of linerixibat on health-related QoL

Conditions and MedDRA coding

Cholestasis

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

IPD for this study will be made available via the Clinical Study Data Request site.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. "1. Male or female participants must be 18 to 80 years of age inclusive, at the time of signing the informed consent in the participant's parent study BAT117213, GLIMMER or GLISTEN Note: if country/site age requirements for consent differ, the more stringent (e.g., higher age) restriction will be required for that country/site."
2. 2. Participants with a diagnosis of PBC and a history of associated pruritus as evidenced by randomization into a prior eligible linerixibat clinical study (BAT117213, GLIMMER or GLISTEN).
3. 3. Participants must have completed the main treatment period(s) in a prior eligible linerixibat clinical study (BAT117213, GLIMMER or GLISTEN).
4. "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, etc.). -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 10.4 Pregnancy Testing. o If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive • Additional requirements for pregnancy testing during and after study intervention are listed in Section 8.2.5 Pregnancy Testing and Section 10.4 Appendix 4: Contraceptive Guidance and Collection of Pregnancy Information. • 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. 5. Capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion criteria 16

1. "1. Screening total bilirubin >2x ULN. Note: Total bilirubin >2x ULN but <3x ULN is acceptable if bilirubin is fractionated and direct bilirubin is <35%"
2. 2. Screening ALT or aspartate aminotransferase (AST) >6x ULN
3. "3. Screening estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m² based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. "
4. 4. Group 2 Participants who meet increased liver chemistry monitoring criteria or any stopping criteria during LLSAT Screening period (GLISTEN Week 28 to Week 32 visit) or temporarily discontinue study treatment due to a drug-related adverse event during the LLSAT Screening period, which did not resolve prior to the time of the LLSAT Baseline Visit. Note: participants that meet increased liver chemistry monitoring criteria or stopping criteria at any timepoint during GLISTEN and restart of study intervention has not been approved by GSK are excluded.
5. 5. Presence of hepatic decompensation (e.g., variceal bleeding, encephalopathy, or ascites).
6. 6. Presence of viral hepatitis B (HBsAg positive) or hepatitis C (anti-HCV positive and RNA detected) infection, primary sclerosing cholangitis (PSC), alcoholic liver disease and/or confirmed hepatocellular carcinoma or biliary cancer.
7. 7. Current clinically significant diarrhea in the investigator’s medical opinion. Polish
8. "8. Current symptomatic cholelithiasis or cholecystitis. Participants with history of cholecystectomy ≥3 months before screening may be eligible for enrollment. "
9. 9. Any current malignancies (including hematologic and solid malignancies)."
10. 10. History of bariatric surgery with ileal bypass at any time, or any bariatric surgery performed in the past 3 years.
11. 11. Any current medical condition (e.g. psychiatric disorder, senility, or dementia), which may affect the participant’s ability to comply with the protocol specified procedures.
12. 12. Use of Obeticholic acid: within 8 weeks prior to the date of the Screening Visit and may not restart until after the End of Study or Early Study Withdrawal.
13. 13. Administration of any other IBAT inhibitor in the 1 month prior to screening until after the End of Study or Early Study Withdrawal.
14. 14. Current enro-llment or participation in any other clinical study (except for GLISTEN) involving an investigational study treatment within 8 weeks prior to the Screening Visit. Note: For participants coming from the GLISTEN study there is no specified waiting period before enrollment into this safety study.
15. 15. QTc >480 msec at screening (12-lead ECG). Note: The QTc is the QT interval corrected for heart rate according to Bazett’s formula (QTcB), Frederica’s formula (QTcF), and/or another method. It is either machine-read or manually over-read
16. 16. Participants with moderate (or greater) alcohol consumption defined as more than one standard drink per day for women and two drinks per day for men; whereby one standard drink is equivalent to: 12 oz beer (5% alcohol), 5 ounces of wine (12% alcohol), or 1.5 ounces of 80 proof spirits (40% alcohol).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. "Frequency and severity of adverse events - From start of treatment (Day1) to end of study or until the follow up phone call after early study withdrawal (Day 7 to 14 post-final dose of IP). Assessments are made on Day 1, Week 1, Months 1, 2, 3, 6, 9, 12, 18, 24, 30, 36, 42, 48 (Additional visits as needed) and final follow phone call on Day 7 to Day 14 post final dose of IP. "

Secondary endpoints 1

1. "1. Change in domain scores of the PBC-40 and BDI-II over time 2. Change in clinically meaningful lab values incl. liver parameters and lipids over time Group 1 only 2. Change in health-related QoL and EQ VAS (EQ-5D-3L) over time. Group 2 only (Responder=R = ≥2, ≥3 and ≥4 points reduction in MIS) 1. R at w24, at w52 of continuous treatment 2. Maintenance of efficacy at w52 for those who were R at w24 3. Change from Baseline in Monthly Sleep and Fatigue Scores over 52 w of cont. treatment"

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Glaxosmithkline Research & Development Limited

Sponsor organisation

Glaxosmithkline Research & Development Limited

Address

G S K House, 980 Great West Road 980 Great West Road

City

Brentford

Postcode

TW8 9GS

Country

United Kingdom

Scientific contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Public contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Third parties 16

Locations

9 EU/EEA countries · 30 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 141 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

13 submissions — initial application plus substantial / non-substantial modifications