A Study to Evaluate the Safety and Tolerability of Marali... | NCT04729751

NCT04729751

ID	Type	Description	Link
2020-004628-40	EudraCT Number

Status Module

Label	Type	Description	Intervention Names
Maralixibat	Experimental	Participants will receive up to 600 μg/kg twice daily (PFIC) or up to 400 μg/kg once daily (ALGS) over 13 weeks in the core study and for the duration of the Long Term Extension (LTE) where applicable.	Drug: Maralixibat

Name	Type	Description	Arm Group Labels	Other Names
Maralixibat	Drug	Maralixibat chloride provided in the form of an oral solution (i.e., 5, 10, 15, and 20 mg/mL) 400 μg/kg maralixibat chloride is equivalent to 380 µg/kg maralixibat free base 600 μg/kg maralixibat chloride is equivalent to 570 µg/kg maralixibat free base

Measure	Description	Time Frame
Frequency of Treatment-emergent Adverse Events [TEAEs]	TEAEs = Treatment-emergent Adverse Events	From Baseline through to Week 13

Measure	Description	Time Frame
Change in Fasting Serum Bile Acid (sBA) Levels	sBA = serum bile acid	From Baseline through to Week 13
To Evaluate the Effect on Liver Enzymes (ALT)	ALT= alanine aminotransferase.

Eligibility Module

Facility	Status	City	State	ZIP	Country	Contacts
Children Hospital LA		Los Angeles	California	90027	United States
University of California - San Francisco

Label	URL
Genetics Home Reference - PFIC	View source
Mirum Pharmaceuticals homepage	View source
Genetics Home Reference - ALGS

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Maralixibat: ALGS	Includes all participants with Alagille Syndrome (ALGS) who received at least one dose of maralixibat. Participants with ALGS received maralixibat doses of either: 200 µg/kg or 400 µg/kg QD.
FG001	Maralixibat: PFIC

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_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Jun 17, 2022

Arm/Group Information

ID	Title	Description
BG000	Maralixibat :ALGS	Participants will receive up to 400 μg/kg once daily (ALGS) over 13 weeks in the core study and for the duration of the Long Term Extension (LTE) where applicable. Maralixibat: Maralixibat chloride provided in the form of an oral solution (i.e., 5, 10, 15, and 20 mg/mL) *400 μg/kg maralixibat chloride is equivalent to 380 µg/kg maralixibat free base
BG001	Maralixibat: PFIC	Participants will receive up to 600 μg/kg twice daily (PFIC) over 13 weeks in the core study and for the duration of the Long Term Extension (LTE) where applicable. Maralixibat: Maralixibat chloride provided in the form of an oral solution (i.e., 5, 10, 15, and 20 mg/mL) *600 μg/kg maralixibat chloride is equivalent to 570 µg/kg maralixibat free base
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00017 BG00110 BG00227

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

Frequency of Treatment-emergent Adverse Events [TEAEs]

TEAEs = Treatment-emergent Adverse Events

Includes all participants with Alagille Syndrome (ALGS) or Progressive Familial Intrahepatic Cholestasis (PFIC) who received at least one dose of maralixibat.

Posted

Count of Participants

Participants

From Baseline through to Week 13

ID	Title	Description
OG000	Maralixibat: ALGS	Includes all participants with Alagille Syndrome (ALGS) who received at least one dose of maralixibat. Participants with ALGS received maralixibat doses of either: 200 µg/kg or 400 µg/kg QD.
OG001	Maralixibat: PFIC	Includes all participants with Progressive Familial Intrahepatic Cholestasis (PFIC) who received at least one dose of maralixibat. Participants with PFIC received maralixibat doses of either: 300 µg/kg QD, 300 µg/kg BID, or 600 µg/kg BID.

Units	Counts
Participants	OG00017 OG00110

Title

Denominators

Categories

At least one TEAE

Title	Measurements
	OG00016 OG00110

TEAE related to study drug

Title	Measurements
	OG000

Secondary

Change in Fasting Serum Bile Acid (sBA) Levels

sBA = serum bile acid

Includes all participants with Alagille Syndrome (ALGS) or Progressive Familial Intrahepatic Cholestasis (PFIC) who received at least one dose of maralixibat.

Posted

Mean

Standard Deviation

µmol/L

From Baseline through to Week 13

ID	Title	Description
OG000	Maralixibat: ALGS	Includes all participants with Alagille Syndrome (ALGS) who received at least one dose of maralixibat. Participants with ALGS received maralixibat doses of either: 200 µg/kg or 400 µg/kg QD.
OG001	Maralixibat: PFIC	Includes all participants with Progressive Familial Intrahepatic Cholestasis (PFIC) who received at least one dose of maralixibat. Participants with PFIC received maralixibat doses of either: 300 µg/kg QD, 300 µg/kg BID, or 600 µg/kg BID.

Units	Counts
Participants	OG000

Secondary

To Evaluate the Effect on Liver Enzymes (ALT)

ALT= alanine aminotransferase.

Includes all participants with Alagille Syndrome (ALGS) or Progressive Familial Intrahepatic Cholestasis (PFIC) who received at least one dose of maralixibat.

Posted

Mean

Standard Deviation

U/L

From Baseline through to Week 13

ID	Title	Description
OG000	Maralixibat: ALGS	Includes all participants with Alagille Syndrome (ALGS) who received at least one dose of maralixibat. Participants with ALGS received maralixibat doses of either: 200 µg/kg to 400 µg/kg QD.
OG001	Maralixibat: PFIC	Includes all participants with Progressive Familial Intrahepatic Cholestasis (PFIC) who received at least one dose of maralixibat. Participants with PFIC received maralixibat doses of either: 300 µg/kg QD, 300 µg/kg BID or 600 µg/kg BID.

Units	Counts
Participants	OG000

Secondary

Change From Baseline to Week 13 in Lipid-Soluble Vitamins (LSVs) - Vitamin E

Change from baseline to Week 13 in vitamin E.

Includes all participants with Alagille Syndrome (ALGS) or Progressive Familial Intrahepatic Cholestasis (PFIC) who received at least one dose of maralixibat.

Posted

Mean

Standard Deviation

mg/L

From Baseline through to Week 13

ID	Title	Description
OG000	Maralixibat: ALGS	Includes all participants with Alagille Syndrome (ALGS) who received at least one dose of maralixibat. Participants with ALGS received maralixibat doses of either: 200 µg/kg or 400 µg/kg QD.
OG001	Maralixibat: PFIC	Includes all participants with Progressive Familial Intrahepatic Cholestasis (PFIC) who received at least one dose of maralixibat. Participants with PFIC received maralixibat doses of either: 300 µg/kg QD, 300 µg/kg BID, or 600 µg/kg BID.

Units	Counts
Participants	OG000

Secondary

Maximum Level of Maralixibat Concentration in Plasma From Baseline to Week 13 for ALGS

BID=twice daily; QD=once daily.

Systemic concentrations of maralixibat in plasma were determined at the following visits:

Approximately 2.5 hours after the morning dose at Week 0/Day 1 of dosing
Before dosing and ~2.5 hours after the morning dose at Week 6, Week 10, and Week 13

Stable dosing occurred at 400 μg/kg QD for ALGS or at the highest tolerated dose.

Note: The values added in section Measured Values are for maralixibat dose of 400 µg/kg QD.

Includes all participants with Alagille Syndrome (ALGS) who received at least one dose of maralixibat.

Posted

Mean

Standard Deviation

ng/mL

At Baseline, Week 6, Week 10, Week 13 or Early Termination Visit

ID	Title	Description
OG000	Maralixibat: ALGS	Includes all participants with Alagille Syndrome (ALGS) who received at least one dose of maralixibat. Participants with ALGS received maralixibat doses of either: 200 μg/kg QD or 400 µg/kg QD.

Units	Counts
Participants	OG000

Secondary

To Evaluate the Effect on Liver Enzymes (AST)

AST= aspartate aminotransferase

Includes all participants with Alagille Syndrome (ALGS) or Progressive Familial Intrahepatic Cholestasis (PFIC) who received at least one dose of maralixibat.

Posted

Mean

Standard Deviation

U/L

From Baseline through to Week 13.

ID	Title	Description
OG000	Maralixibat: ALGS	Includes all participants with Alagille Syndrome (ALGS) who received at least one dose of maralixibat. Participants with ALGS received maralixibat doses of either: 200 µg/kg or 400 µg/kg QD.
OG001	Maralixibat: PFIC	Includes all participants with Progressive Familial Intrahepatic Cholestasis (PFIC) who received at least one dose of maralixibat. Participants with PFIC received maralixibat doses of either: 300 µg/kg QD, 300 µg/kg BID, or 600 µg/kg BID.

Units	Counts
Participants	OG000

Secondary

To Evaluate the Effect on Bilirubin

Bilirubin

Includes all participants with Alagille Syndrome (ALGS) or Progressive Familial Intrahepatic Cholestasis (PFIC) who received at least one dose of maralixibat.

Posted

Mean

Standard Deviation

µmol/L

From Baseline through to Week 13

ID	Title	Description
OG000	Maralixibat: ALGS	Includes all participants with Alagille Syndrome (ALGS) who received at least one dose of maralixibat. Participants with ALGS received maralixibat doses of either: 200 μg/kg or 400 µg/kg QD.
OG001	Maralixibat: PFIC	Includes all participants with Progressive Familial Intrahepatic Cholestasis (PFIC) who received at least one dose of maralixibat. Participants with PFIC received maralixibat doses of either: 300 μg/kg QD, 300 μg/kg BID or 600 µg/kg BID.

Units	Counts
Participants	OG000

Secondary

Change From Baseline to Week 13 in Lipid-Soluble Vitamins (LSVs) - Vitamin A

Change from baseline to Week 13 in vitamin A

Includes all participants with Alagille Syndrome (ALGS) or Progressive Familial Intrahepatic Cholestasis (PFIC) who received at least one dose of maralixibat.

Posted

Mean

Standard Deviation

umol/L

From Baseline through to Week 13

ID	Title	Description
OG000	Maralixibat: ALGS	Includes all participants with Alagille Syndrome (ALGS) who received at least one dose of maralixibat. Participants with ALGS received maralixibat doses of either: 200 µg/kg or 400 µg/kg QD.
OG001	Maralixibat: PFIC	Includes all participants with Progressive Familial Intrahepatic Cholestasis (PFIC) who received at least one dose of maralixibat. Participants with PFIC received maralixibat doses of either: 300 μg/kg QD, 300 μg/kg BID or 600 µg/kg BID.

Units	Counts
Participants	OG000

Secondary

Change From Baseline to Week 13 in Lipid-Soluble Vitamins (LSVs) - Vitamins D and K

Change from baseline to Week 13 in vitamins D and K.

Includes all participants with Alagille Syndrome (ALGS) or Progressive Familial Intrahepatic Cholestasis (PFIC) who received at least one dose of maralixibat.

Posted

Mean

Standard Deviation

nmol/L

From Baseline through to Week 13

ID	Title	Description
OG000	Maralixibat: ALGS	Includes all participants with Alagille Syndrome (ALGS) who received at least one dose of maralixibat. Participants with ALGS received maralixibat doses of either: 200 µg/kg or 400 µg/kg QD.
OG001	Maralixibat: PFIC	Includes all participants with Progressive Familial Intrahepatic Cholestasis (PFIC) who received at least one dose of maralixibat. Participants with PFIC received maralixibat doses of either: 300 μg/kg QD, 300 μg/kg BID or 600 µg/kg BID.

Units	Counts
Participants	OG000

Secondary

Maximum Level of Maralixibat Concentration in Plasma From Baseline to Week 13 for PFIC

BID=twice daily; QD=once daily.

Systemic concentrations of maralixibat in plasma were determined at the following visits:

Approximately 2.5 hours after the morning dose at Week 0/Day 1 of dosing
Before dosing and ~2.5 hours after the morning dose at Week 6, Week 10, and Week 13

Stable dosing occurred at 300 μg/kg QD, 300 μg/kg BID and 600 μg/kg BID for PFIC or at the highest tolerated dose.

Note: The values added in section Measured Values are for maralixibat dose of 600 µg/kg BID.

Includes all participants with Progressive Familial Intrahepatic Cholestasis (PFIC) who received at least one dose of maralixibat.

Posted

Mean

Standard Deviation

ng/mL

At Baseline, Week 6, Week 10, Week 13 or Early Termination Visit

ID	Title	Description
OG000	Maralixibat: PFIC	Includes all participants with Progressive Familial Intrahepatic Cholestasis (PFIC) who received at least one dose of maralixibat. Participants with PFIC received maralixibat doses of either: 300 µg/kg QD, 300 µg/kg BID, or 600 µg/kg BID.

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	Maralixibat: ALGS	Includes all participants with Alagille Syndrome (ALGS) who received at least one dose of maralixibat. Participants with ALGS received maralixibat doses of either: 200 µg/kg or 400 µg/kg QD.	0	17	6	17	16	17
EG001	Maralixibat: PFIC	Includes all participants with Progressive Familial Intrahepatic Cholestasis (PFIC) who received at least one dose of maralixibat. Participants with PFIC received maralixibat doses of either: 300 μg/kg QD, 300 μg/kg BID or 600 µg/kg BID.	0	10	2	10	10	10

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Crying	General disorders	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected10 at risk
Pyrexia	General disorders	MedDRA 22.1	Systematic Assessment	EG0002 events1 affected17 at risk EG0010 events0 affected10 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected10 at risk
Infantile colic	General disorders	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected10 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected17 at risk EG0011 events1 affected10 at risk
Abdominal sepsis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected17 at risk EG0011 events1 affected10 at risk
Adenovirus infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected17 at risk EG0011 events1 affected10 at risk
Appendicitis perforated	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected17 at risk EG0011 events1 affected10 at risk
Corona virus infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected10 at risk
Gastroenteritis adenovirus	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected17 at risk EG0011 events1 affected10 at risk
Influenza	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected17 at risk EG0011 events1 affected10 at risk
Otitis media acute	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected10 at risk
Pneumonia	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0002 events1 affected17 at risk EG0010 events0 affected10 at risk
Sepsis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected10 at risk
Varicella	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected10 at risk
Viral infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0002 events1 affected17 at risk EG0010 events0 affected10 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Investigations	Investigations	MedDRA 22.1	Systematic Assessment	EG0005 events3 affected17 at risk EG0016 events3 affected10 at risk
Injury, poisoning and procedural complications	Injury, poisoning and procedural complications	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected17 at risk EG0014 events2 affected10 at risk
Nervous system disorders	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0002 events2 affected17 at risk EG0012 events2 affected10 at risk
Coagulopathy	Blood and lymphatic system disorders	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected17 at risk EG0016 events3 affected10 at risk
Pyrexia	General disorders	MedDRA 22.1	Systematic Assessment	EG0008 events3 affected17 at risk EG0012 events2 affected10 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG00015 events7 affected17 at risk EG0018 events4 affected10 at risk
Vomiting	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0005 events2 affected17 at risk EG0018 events5 affected10 at risk
Teething	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0007 events3 affected17 at risk EG0013 events2 affected10 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0004 events3 affected17 at risk EG0011 events1 affected10 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0005 events4 affected17 at risk EG0012 events2 affected10 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0003 events2 affected17 at risk EG0014 events3 affected10 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0002 events2 affected17 at risk EG0010 events0 affected10 at risk
Skin and subcutaneous tissue disorders	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0005 events4 affected17 at risk EG0012 events2 affected10 at risk
Nasopharyngitis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0009 events6 affected17 at risk EG0016 events4 affected10 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG00012 events4 affected17 at risk EG0015 events4 affected10 at risk
Viral infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0004 events4 affected17 at risk EG0017 events4 affected10 at risk
Corona virus infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0003 events3 affected17 at risk EG0012 events2 affected10 at risk
Rhinitis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0003 events3 affected17 at risk EG0012 events2 affected10 at risk
Ear infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0008 events4 affected17 at risk EG0010 events0 affected10 at risk
Gastroenteritis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0002 events2 affected17 at risk EG0011 events1 affected10 at risk
Influenza	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected17 at risk EG0012 events1 affected10 at risk
Conjunctivitis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0002 events2 affected17 at risk EG0010 events0 affected10 at risk
Otitis media	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0002 events2 affected17 at risk EG0010 events0 affected10 at risk
Respiratory tract infection viral	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0002 events2 affected17 at risk EG0010 events0 affected10 at risk
Hypervitaminosis D	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0002 events2 affected17 at risk EG0010 events0 affected10 at risk

ID	Term
C535933	Cholestasis, progressive familial intrahepatic 1
D016738	Alagille Syndrome
D001649	Bile Duct Diseases
D008107	Liver Diseases
D001660	Biliary Tract Diseases

ID	Term
D002780	Cholestasis, Intrahepatic
D002779	Cholestasis
D004066	Digestive System 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