Efficacy and Safety of Odevixibat in Patients With Alagil... | NCT04674761

Status Module

Label	Type	Description	Intervention Names
Odevixibat (A4250)	Experimental	Capsules for oral administration once daily for 24 weeks.	Drug: Odevixibat
Placebo	Placebo Comparator	Capsules for oral administration (to match active) once daily for 24 weeks.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Odevixibat	Drug	Odevixibat is a small molecule and selective inhibitor of IBAT.	Odevixibat (A4250)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Scratching Score	Change from baseline in average AM (measured after waking up) and PM (measured before bedtime) scratching score to Month 6 as measured by the Albireo Observer-Reported Outcome (ObsRO) Instrument. The ObsRO instrument was used to assess severity of observed scratching twice a day (AM and PM) with scores from 0 to 4 where 0 is no scratching and 4 is worst possible scratching.	Change from baseline for each four-week average pruritis score to Month 6 (Weeks 21 to 24), in which baseline was calculated based on the 14 days before the start of treatment.

Secondary Outcomes

Measure	Description	Time Frame
Serum Bile Acid Levels	Change in serum bile acid levels (μmol/L) from baseline to average of week 20 and 24	Change from baseline to average of week 20 and 24, where baseline was calculated by averaging the last two values preceding start of treatment, and average of Week 20 and Week 24 was defined as the average of Week 20 and Week 24 values.

Eligibility Module

Facility	Status	City	State	ZIP	Country	Contacts
University of California - San Francisco		San Francisco	California	94158	United States
Johns Hopkins Hospital

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
38670135	Derived	Ovchinsky N, Aumar M, Baker A, Baumann U, Bufler P, Cananzi M, Czubkowski P, Durmaz O, Fischer R, Indolfi G, Karnsakul WW, Lacaille F, Lee WS, Maggiore G, Rosenthal P, Ruiz M, Sokal E, Sturm E, van der Woerd W, Verkade HJ, Wehrman A, Clemson C, Yu Q, Ni Q, Ruvido J, Manganaro S, Mattsson JP. Efficacy and safety of odevixibat in patients with Alagille syndrome (ASSERT): a phase 3, double-blind, randomised, placebo-controlled trial. Lancet Gastroenterol Hepatol. 2024 Jul;9(7):632-645. doi: 10.1016/S2468-1253(24)00074-8. Epub 2024 Apr 23.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Odevixibat (A4250)	Capsules for oral administration once daily for 24 weeks (120 μg/kg/day). Odevixibat: Odevixibat is a small molecule and selective inhibitor of IBAT.
FG001	Placebo

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Aug 28, 2020	Sep 7, 2023

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG00035 BG00117 BG00252
Between 18 and 65 years

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG0006.73± 3.780 BG0015.40± 4.411 BG002

Age, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
< 10 years	BG00029 BG00113 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00014 BG00111 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
White	BG00030 BG00113 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG0007 BG0014 BG002

Genetic Mutation

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
JAG1	BG00032 BG00116 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in Scratching Score

Change from baseline in average AM (measured after waking up) and PM (measured before bedtime) scratching score to Month 6 as measured by the Albireo Observer-Reported Outcome (ObsRO) Instrument. The ObsRO instrument was used to assess severity of observed scratching twice a day (AM and PM) with scores from 0 to 4 where 0 is no scratching and 4 is worst possible scratching.

Posted

Least Squares Mean

Standard Error

score on a scale

Change from baseline for each four-week average pruritis score to Month 6 (Weeks 21 to 24), in which baseline was calculated based on the 14 days before the start of treatment.

ID	Title	Description
OG000	Odevixibat (A4250)	Capsules for oral administration once daily for 24 weeks. Odevixibat: Odevixibat is a small molecule and selective inhibitor of IBAT.
OG001	Placebo	Capsules for oral administration (to match active) once daily for 24 weeks. Placebo: Placebo identical in appearance to experimental drug (odevixibat).

Units	Counts
Participants	OG00035 OG00117

Title

Denominators

Categories

Title	Measurements
	OG000-1.69± 0.174 OG001-0.8± 0.233

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The analysis is based on a mixed model for repeated measures (MMRM) using a restricted maximum likelihood (REML) with baseline score as a covariate, and baseline age stratification, baseline direct bilirubin, treatment group, time (in months), and treatment-by-time interaction as fixed effects. One-sided p-value was reported.	Mixed Models Analysis		0.0012		LS mean difference	-0.88	Standard Error of the Mean	0.277	2-Sided	95	-1.44	-0.33					Superiority

Secondary

Serum Bile Acid Levels

Change in serum bile acid levels (μmol/L) from baseline to average of week 20 and 24

Posted

Least Squares Mean

Standard Error

μmol/L

Change from baseline to average of week 20 and 24, where baseline was calculated by averaging the last two values preceding start of treatment, and average of Week 20 and Week 24 was defined as the average of Week 20 and Week 24 values.

ID	Title	Description
OG000	Odevixibat (A4250)	Capsules for oral administration once daily for 24 weeks. Odevixibat: Odevixibat is a small molecule and selective inhibitor of IBAT.
OG001	Placebo	Capsules for oral administration (to match active) once daily for 24 weeks. Placebo: Placebo identical in appearance to experimental drug (odevixibat).

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Odevixibat (A4250)	Capsules for oral administration once daily for 24 weeks. Odevixibat: Odevixibat is a small molecule and selective inhibitor of IBAT.	0	35	5	35	26	35
EG001	Placebo	Capsules for oral administration (to match active) once daily for 24 weeks. Placebo: Placebo identical in appearance to experimental drug (odevixibat).	0	17	2	17	12	17

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
International normalised ratio increased	Investigations	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected35 at risk EG0010 events0 affected17 at risk
Pyrexia	General disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected35 at risk EG0011 events1 affected17 at risk
Cerumen impaction	Ear and labyrinth disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected35 at risk EG0011 events1 affected17 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 25.0	Non-systematic Assessment	EG0002 events1 affected35 at risk EG0010 events0 affected17 at risk
Constipation	Gastrointestinal disorders	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected35 at risk EG0010 events0 affected17 at risk
Haematemesis	Gastrointestinal disorders	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected35 at risk EG0010 events0 affected17 at risk
Otitis media chronic	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected35 at risk EG0011 events1 affected17 at risk
Pneumonia	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected35 at risk EG0010 events0 affected17 at risk
Rhinovirus infection	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected35 at risk EG0010 events0 affected17 at risk
Subcutaneous abscess	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected35 at risk EG0011 events1 affected17 at risk
Tonsillitis	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected35 at risk EG0010 events0 affected17 at risk
Adenoidal hypertrophy	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected35 at risk EG0011 events1 affected17 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia macrocytic	Blood and lymphatic system disorders	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected35 at risk EG0010 events0 affected17 at risk
Coagulopathy	Blood and lymphatic system disorders	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected35 at risk EG0010 events0 affected17 at risk
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected35 at risk EG0010 events0 affected17 at risk
Cataract cortical	Eye disorders	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected35 at risk EG0010 events0 affected17 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 25.0	Non-systematic Assessment	EG0004 events4 affected35 at risk EG0011 events1 affected17 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 25.0	Non-systematic Assessment	EG0002 events1 affected35 at risk EG0010 events0 affected17 at risk
Aphthous ulcer	Gastrointestinal disorders	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected35 at risk EG0010 events0 affected17 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 25.0	Non-systematic Assessment	EG00011 events10 affected35 at risk EG0011 events1 affected17 at risk
Faeces discoloured	Gastrointestinal disorders	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected35 at risk EG0010 events0 affected17 at risk
Faeces soft	Gastrointestinal disorders	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected35 at risk EG0010 events0 affected17 at risk
Frequent bowel movements	Gastrointestinal disorders	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected35 at risk EG0010 events0 affected17 at risk
Nausea	Gastrointestinal disorders	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected35 at risk EG0010 events0 affected17 at risk
Vomiting	Gastrointestinal disorders	MedDRA 25.0	Non-systematic Assessment	EG0002 events2 affected35 at risk EG0011 events1 affected17 at risk
Asthenia	General disorders	MedDRA 25.0	Non-systematic Assessment	EG0002 events2 affected35 at risk EG0010 events0 affected17 at risk
Fatigue	General disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected35 at risk EG0011 events1 affected17 at risk
Pyrexia	General disorders	MedDRA 25.0	Non-systematic Assessment	EG0008 events8 affected35 at risk EG0017 events4 affected17 at risk
Jaundice	Hepatobiliary disorders	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected35 at risk EG0010 events0 affected17 at risk
Hypersensitivity	Immune system disorders	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected35 at risk EG0010 events0 affected17 at risk
Seasonal allergy	Immune system disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected35 at risk EG0011 events1 affected17 at risk
Bronchitis	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0004 events3 affected35 at risk EG0010 events0 affected17 at risk
COVID-19	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0005 events5 affected35 at risk EG0014 events4 affected17 at risk
Conjunctivitis	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0003 events2 affected35 at risk EG0010 events0 affected17 at risk
Gastroenteritis	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0002 events2 affected35 at risk EG0010 events0 affected17 at risk
Influenza	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected35 at risk EG0011 events1 affected17 at risk
Nasopharyngitis	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0004 events2 affected35 at risk EG0011 events1 affected17 at risk
Otitis externa	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected35 at risk EG0011 events1 affected17 at risk
Otitis media	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected35 at risk EG0010 events0 affected17 at risk
Pharyngitis	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected35 at risk EG0010 events0 affected17 at risk
Respiratory tract infection	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0003 events3 affected35 at risk EG0011 events1 affected17 at risk
Subcutaneous abscess	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected35 at risk EG0011 events1 affected17 at risk
Tonsillitis	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected35 at risk EG0010 events0 affected17 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0003 events3 affected35 at risk EG0012 events2 affected17 at risk
Viral infection	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected35 at risk EG0011 events1 affected17 at risk
Viral rash	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected35 at risk EG0011 events1 affected17 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected35 at risk EG0011 events1 affected17 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected35 at risk EG0010 events0 affected17 at risk
Ligament sprain	Injury, poisoning and procedural complications	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected35 at risk EG0010 events0 affected17 at risk
Vaccination complication	Injury, poisoning and procedural complications	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected35 at risk EG0011 events1 affected17 at risk
Alanine aminotransferase increased	Investigations	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected35 at risk EG0010 events0 affected17 at risk
Blood pressure diastolic increased	Investigations	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected35 at risk EG0011 events1 affected17 at risk
Blood triglycerides increased	Investigations	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected35 at risk EG0010 events0 affected17 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected35 at risk EG0010 events0 affected17 at risk
Hepatic enzyme increased	Investigations	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected35 at risk EG0011 events1 affected17 at risk
International normalised ratio increased	Investigations	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected35 at risk EG0012 events2 affected17 at risk
Platelet count decreased	Investigations	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected35 at risk EG0010 events0 affected17 at risk
Vitamin A decreased	Investigations	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected35 at risk EG0010 events0 affected17 at risk
Vitamin E decreased	Investigations	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected35 at risk EG0010 events0 affected17 at risk
Weight decreased	Investigations	MedDRA 25.0	Non-systematic Assessment	EG0002 events2 affected35 at risk EG0010 events0 affected17 at risk
Hypophagia	Metabolism and nutrition disorders	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected35 at risk EG0010 events0 affected17 at risk
Vitamin D deficiency	Metabolism and nutrition disorders	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected35 at risk EG0011 events1 affected17 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected35 at risk EG0010 events0 affected17 at risk
Bell's palsy	Nervous system disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected35 at risk EG0011 events1 affected17 at risk
Headache	Nervous system disorders	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected35 at risk EG0010 events0 affected17 at risk
Proteinuria	Renal and urinary disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected35 at risk EG0011 events1 affected17 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected35 at risk EG0010 events0 affected17 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Non-systematic Assessment	EG0004 events3 affected35 at risk EG0011 events1 affected17 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected35 at risk EG0012 events2 affected17 at risk
Nasal turbinate hypertrophy	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Non-systematic Assessment	EG0000 events0 affected35 at risk EG0011 events1 affected17 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected35 at risk EG0010 events0 affected17 at risk
Pharyngeal inflammation	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected35 at risk EG0010 events0 affected17 at risk
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Non-systematic Assessment	EG0002 events1 affected35 at risk EG0010 events0 affected17 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected35 at risk EG0011 events1 affected17 at risk
Skin lesion	Skin and subcutaneous tissue disorders	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected35 at risk EG0010 events0 affected17 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 25.0	Non-systematic Assessment	EG0001 events1 affected35 at risk EG0010 events0 affected17 at risk
Haematoma	Vascular disorders	MedDRA 25.0	Non-systematic Assessment	EG0003 events3 affected35 at risk EG0010 events0 affected17 at risk

ID	Term
D002780	Cholestasis, Intrahepatic
D002779	Cholestasis
D001649	Bile Duct Diseases
D001660	Biliary Tract Diseases
D004066	Digestive System Diseases
D008107	Liver Diseases
D006330	Heart Defects, Congenital
D018376	Cardiovascular Abnormalities
D002318	Cardiovascular Diseases
D000015	Abnormalities, Multiple
D000013	Congenital Abnormalities
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D030342	Genetic Diseases, Inborn

ID	Title	Description
BG000	Odevixibat (A4250)	Capsules for oral administration once daily for 24 weeks (120 μg/kg/day). Odevixibat: Odevixibat is a small molecule and selective inhibitor of IBAT.
BG001	Placebo	Capsules for oral administration (to match active) once daily for 24 weeks. Placebo: Placebo identical in appearance to experimental drug (odevixibat).
BG002	Total	Total of all reporting groups