Clinical Trials Register

Summary
EudraCT Number:	2019-003807-37
Sponsor's Protocol Code Number:	A4250-011
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2020-10-21
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2019-003807-37

A.3

Full title of the trial

A Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Odevixibat (A4250) in Children with Biliary Atresia Who Have Undergone a Kasai Hepatoportoenterostomy (BOLD)

Studio in doppio cieco, randomizzato, controllato con placebo volto a valutare l'efficacia e la sicurezza di odevixibat (A4250) in bambini affetti da atresia delle vie biliari che sono stati sottoposti a epatoportoenterostomia secondo Kasai (BOLD)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

This Study Will Investigate the Efficacy and Safety of Odevixibat in Children with Biliary Atresia Who Have Undergone a Kasai HPE

Questo studio esaminerà l'efficacia e la sicurezza di Odevixibat in bambini affetti da atresia delle vie biliari che sono stati sottoposti a HPE Kasai

A.3.2

Name or abbreviated title of the trial where available

BOLD

A.4.1

Sponsor's protocol code number

A4250-011

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	ALBIREO AB
B.1.3.4	Country	Sweden
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Albireo AB
B.5.2	Functional name of contact point	Clinical Operations Department
B.5.3	Address:
B.5.3.1	Street Address	Arvid Wallgrens backe 20
B.5.3.2	Town/ city	Göteborg
B.5.3.3	Post code	41346
B.5.3.4	Country	Sweden
B.5.4	Telephone number	0046317411480
B.5.5	Fax number	004631820223
B.5.6	E-mail	medinfo@albireopharma.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EMA/OD/165/18
D.3 Description of the IMP
D.3.1	Product name	Odevixibat
D.3.2	Product code	[A4250]
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	Yes
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Odevixibat
D.3.9.1	CAS number	501692-44-0
D.3.9.2	Current sponsor code	A4250
D.3.9.4	EV Substance Code	SUB126128
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	200
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EMA/OD/165/18
D.3 Description of the IMP
D.3.1	Product name	Odevixibat
D.3.2	Product code	[A4250]
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	Yes
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Odevixibat
D.3.9.1	CAS number	501692-44-0
D.3.9.2	Current sponsor code	A4250
D.3.9.4	EV Substance Code	SUB126128
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	600
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EMA/OD/165/18
D.3 Description of the IMP
D.3.1	Product name	Odevixibat
D.3.2	Product code	[A4250]
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	Yes
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Odevixibat
D.3.9.1	CAS number	501692-44-0
D.3.9.2	Current sponsor code	A4250
D.3.9.4	EV Substance Code	SUB126128
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	200
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule, hard
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Biliary Atresia

Atresia biliare

E.1.1.1

Medical condition in easily understood language

Childhood disease of the liver in which one or more bile ducts are abnormally narrow, blocked, or absent.

Malattia infantile del fegato in cui uno o più dotti biliari sono anormalmente stretti, bloccati o assenti.

E.1.1.2

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10004653
E.1.2	Term	Biliary atresia
E.1.2	System Organ Class	100000004850

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective is to evaluate the efficacy of repeated once-daily doses of odevixibat versus placebo in children with biliary atresia (BA) post Kasai hepatoportoenterostomy(HPE) based on survival with native liver after 104 weeks of study treatment.

L'obiettivo primario è valutare l'efficacia di dosi QD ripetute di odevixibat rispetto al placebo in bambini affetti da atresia delle vie biliari (AVB) successivamente a epatoportoenterostomia secondo Kasai (hepatoPortoEnterostomy, HPE) in base alla sopravvivenza con fegato nativo dopo 104 settimane di trattamento in studio.

E.2.2

Secondary objectives of the trial

- To evaluate the effect of odevixibat compared to placebo on the time to onset of sentinel events.
- To evaluate the effect of odevixibat compared to placebo on total bilirubin after 13, 26, 52, and 104 weeks of study treatment.
- To evaluate the effect of odevixibat compared to placebo on serum bile acids after 13, 26, 52, and 104 weeks of study treatment.
- To assess the long-term safety and tolerability of repeated daily doses of odevixibat compared to placebo for 104 weeks in children with BA post Kasai HPE.

- Valutare l'effetto di odevixibat rispetto al placebo sul tempo all'insorgenza di eventi sentinella.
- Valutare l'effetto di odevixibat rispetto al placebo sulla bilirubina totale dopo 13, 26, 52 e 104 settimane di trattamento in studio.
- Valutare l'effetto di odevixibat rispetto al placebo sugli acidi biliari nel siero dopo 13, 26, 52 e 104 settimane di trattamento in studio.
- Valutare la sicurezza e la tollerabilità a lungo termine di dosi giornaliere ripetute di odevixibat rispetto al placebo per 104 settimane in bambini affetti da AVB, che sono stati sottoposti a HPE secondo Kasai.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. A male or female patient with a clinical diagnosis of BA
2. Age at Kasai HPE =90 days
3. Eligible to start study treatment within 3 weeks post-Kasai HPE

1. Paziente maschio o femmina con diagnosi clinica di AVB
2. Età all'HPE secondo Kasai =90 giorni
3. Eleggibilità a iniziare il trattamento in studio entro 3 settimane dall'HPE secondo Kasai

E.4

Principal exclusion criteria

1. Patients with intractable ascites
2. Ileal resection surgery
3. ALT =10× upper limit of normal (ULN) at screening
4. Patient on total parenteral nutrition at randomization
5. Acute ascending cholangitis (patients may be randomized after resolution of acute ascending cholangitis)
6. Choledochal cystic disease

1. Pazienti con ascite intrattabile
2. Chirurgia di resezione ileale
3. ALT =10 × limite superiore del normale (ULN) allo screening
4. Paziente su nutrizione parenterale totale alla randomizzazione
5. Colangite acuta ascendente (i pazienti possono essere randomizzati dopo la risoluzione della colangite acuta ascendente)
6. Malattia cistica coledocica

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is the proportion of patients who are alive and have not undergone a liver transplant after 104 weeks of study treatment.

L'endpoint primario di efficacia consiste nella percentuale di pazienti vivi e che non hanno subito un trapianto di fegato dopo 104 settimane di trattamento in studio.

E.5.1.1

Timepoint(s) of evaluation of this end point

104 weeks

104 settimane

E.5.2

Secondary end point(s)

1. Time to onset of any sentinel events.
2. Total bilirubin level after 13, 26, 52, and 104 weeks of study
treatment.
3. Serum bile acid level after 13, 26, 52, and 104 weeks of study
treatment.
4. Safety parameters including AEs, SAEs, findings on physical
examination, laboratory assessments and abdominal ultrasound, and
stool frequency.

1. Tempo all'insorgenza di qualsiasi evento sentinella.
2. Livello di bilirubina totale dopo 13, 26, 52 e 104 settimane di trattamento in studio.
3. Livello degli acidi biliari nel siero dopo 13, 26, 52 e 104 settimane di trattamento in studio.
4. Parametri di sicurezza, tra cui AE, eventi avversi seri (SAE), reperti all'esame obiettivo, valutazioni di laboratorio, ecografia addominale e frequenza di evacuazione.

E.5.2.1

Timepoint(s) of evaluation of this end point

13, 26, 52 and 104 weeks.

13, 26, 52 e 104 settimane.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Belgium

Canada

China

Denmark

France

Germany

Hungary

Israel

Italy

Korea, Republic of

Malaysia

Netherlands

New Zealand

Poland

Spain

Taiwan

Turkey

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The end of the study is defined as follows:
• End of study in one country: last patient last visit (LPLV) in the country and sites in the country are closed
• End of study globally: LPLV globally and all study sites closed

La fine dello studio è definita come segue:
• Fine dello studio in un paese: ultima visita dell'ultimo paziente (LPLV) nel
paese e centri nel paese chiusi
• Fine dello studio a livello globale: LPLV a livello globale e tutti i centri di studio chiusi

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

Yes

F.1.1.4.1

Number of subjects for this age range:

200

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Subjects under age incapable of giving consent personally.

Soggetti minorenni incapaci di dare il consenso personalmente.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

200

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Following completion of this study, patients will be eligible to receive open-label odevixibat 120 µg/kg/day through an open-label extension study.

Dopo il completamento di questo studio, i pazienti avranno diritto a ricevere odevixibat in aperto 120 µg / kg / giorno attraverso uno studio di estensione in aperto.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-09-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-05-25

P. End of Trial
P.	End of Trial Status	Ongoing

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