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

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04950127

Collaborator

(none)

230

Enrollment

Locations

Arms

26.9

Anticipated Duration (Months)

2.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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

Study Design

Study Type:

Interventional

Anticipated 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.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 :

Aug 27, 2021

Anticipated Primary Completion Date :

Nov 23, 2023

Anticipated Study Completion Date :

Nov 23, 2023

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

Change from Baseline in Monthly Itch Scores over 24 weeks using Numerical Rating Scale (NRS) [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

Change from Baseline in Mean Worst Daily Itch score at Week 2 [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 [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 [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 [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 [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 [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 [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 [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 [Baseline and Week 24]
Change from Baseline in ALP at Week 24 will be evaluated.
Change from Baseline in bilirubin at Week 24 [Baseline and Week 24]
Change from Baseline in bilirubin at Week 24 will be evaluated.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Culver City	California	United States	90230
2	GSK Investigational Site	Los Angeles	California	United States	90033
3	GSK Investigational Site	Los Angeles	California	United States	90048
4	GSK Investigational Site	Sacramento	California	United States	95817
5	GSK Investigational Site	San Francisco	California	United States	94143
6	GSK Investigational Site	Hialeah	Florida	United States	33012
7	GSK Investigational Site	Miami	Florida	United States	33032
8	GSK Investigational Site	Miami	Florida	United States	33136
9	GSK Investigational Site	Miami	Florida	United States	33165
10	GSK Investigational Site	Orlando	Florida	United States	32825
11	GSK Investigational Site	Tamarac	Florida	United States	33321
12	GSK Investigational Site	Novi	Michigan	United States	48377
13	GSK Investigational Site	Jackson	Mississippi	United States	39216
14	GSK Investigational Site	Omaha	Nebraska	United States	68198-2000
15	GSK Investigational Site	Durham	North Carolina	United States	27710
16	GSK Investigational Site	Columbus	Ohio	United States	43210
17	GSK Investigational Site	Houston	Texas	United States	77054
18	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Buenos Aires	Argentina	C1056ABJ
19	GSK Investigational Site	San Nicolas	Buenos Aires	Argentina	B2900DMH
20	GSK Investigational Site	Rosario	Santa Fe	Argentina	S2002KDT
21	GSK Investigational Site	Santa Fe		Argentina	3000
22	GSK Investigational Site	Brussels		Belgium	1070
23	GSK Investigational Site	Gent		Belgium	9000
24	GSK Investigational Site	Salvador	Bahia	Brazil	40110-160
25	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul	Brazil	90035003
26	GSK Investigational Site	Botucatu	São Paulo	Brazil	18618686
27	GSK Investigational Site	Sofia		Bulgaria	1618
28	GSK Investigational Site	Ottawa	Ontario	Canada	K1H 8L6
29	GSK Investigational Site	Toronto	Ontario	Canada	M5G 2C4
30	GSK Investigational Site	Guangzhou	Guangdong	China	510630
31	GSK Investigational Site	Nanjing	Jiangsu	China	210003
32	GSK Investigational Site	Changchun	Jilin	China	130021
33	GSK Investigational Site	Beijing		China	100032
34	GSK Investigational Site	Shanghai		China	200127
35	GSK Investigational Site	Clichy		France	92110
36	GSK Investigational Site	Créteil cedex		France	94010
37	GSK Investigational Site	Grenoble cedex 9		France	38043
38	GSK Investigational Site	Lille cedex		France	59037
39	GSK Investigational Site	Montpellier Cedex 5		France	34295
40	GSK Investigational Site	Paris		France	75012
41	GSK Investigational Site	Erlangen	Bayern	Germany	91054
42	GSK Investigational Site	Essen	Nordrhein-Westfalen	Germany	45147
43	GSK Investigational Site	Muenster	Nordrhein-Westfalen	Germany	48149
44	GSK Investigational Site	Modena	Emilia-Romagna	Italy	41126
45	GSK Investigational Site	Milano	Lombardia	Italy	20142
46	GSK Investigational Site	Monza (MB)	Lombardia	Italy	20900
47	GSK Investigational Site	Rozzano	Lombardia	Italy	20089
48	GSK Investigational Site	Negrar Di Valpolicella	Veneto	Italy	37024
49	GSK Investigational Site	Ehime		Japan	791-0295
50	GSK Investigational Site	Fukui		Japan	918-8503
51	GSK Investigational Site	Hiroshima		Japan	730-8619
52	GSK Investigational Site	Hiroshima		Japan	734-8551
53	GSK Investigational Site	Hokkaido		Japan	006-8555
54	GSK Investigational Site	Ibaraki		Japan	300-0028
55	GSK Investigational Site	Kagawa		Japan	760-8557
56	GSK Investigational Site	Kanagawa		Japan	259-1143
57	GSK Investigational Site	Nagano		Japan	390-8621
58	GSK Investigational Site	Nagasaki		Japan	856-8562
59	GSK Investigational Site	Nara		Japan	634-8522
60	GSK Investigational Site	Shizuoka		Japan	431-3192
61	GSK Investigational Site	Tokyo		Japan	113-8603
62	GSK Investigational Site	Tokyo		Japan	162-8655
63	GSK Investigational Site	Tokyo		Japan	173-8606
64	GSK Investigational Site	Mexico, City	Ciudad De Mexico	Mexico	06700
65	GSK Investigational Site	Monterrey	Nuevo León	Mexico	64020
66	GSK Investigational Site	Czestochowa		Poland	42-217
67	GSK Investigational Site	Myslowice		Poland	41-400
68	GSK Investigational Site	Warszawa		Poland	03-712
69	GSK Investigational Site	Wroclaw		Poland	51-162
70	GSK Investigational Site	Kemerovo		Russian Federation	650000
71	GSK Investigational Site	Moscow		Russian Federation	111123
72	GSK Investigational Site	Moscow		Russian Federation	119121
73	GSK Investigational Site	Novosibirsk		Russian Federation	630005
74	GSK Investigational Site	Saint-Petersburg		Russian Federation	197110
75	GSK Investigational Site	Samara		Russian Federation	443063
76	GSK Investigational Site	Ulan-Ude		Russian Federation	670002
77	GSK Investigational Site	Redhill	Surrey	United Kingdom	RH1 5RH
78	GSK Investigational Site	Basingstoke		United Kingdom	RG24 9AA
79	GSK Investigational Site	Hull		United Kingdom	HU3 2JZ
80	GSK Investigational Site	Liverpool		United Kingdom	L9 7AL
81	GSK Investigational Site	London		United Kingdom	NW3 2QG
82	GSK Investigational Site	Plymouth		United Kingdom	PL6 8DH
83	GSK Investigational Site	Reading		United Kingdom	RG1 5AN
84	GSK Investigational Site	Southampton		United Kingdom	SO16 6YD