Clinical Trials Register

Summary
EudraCT Number:	2014-004693-42
Sponsor's Protocol Code Number:	747-206
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2022-01-07
Trial results	View 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

France - ANSM

A.2

EudraCT number

2014-004693-42

A.3

Full title of the trial

A Multicenter, Open-Label, Single- and Multiple-Dose, Dose-Finding Study, with an Optional Open-Label Extension to Assess the Safety, Tolerability, and Pharmacokinetics of Obeticholic Acid in Pediatric Subjects with Biliary Atresia

A.3.1

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

A study to look at how the study drug Obeticholic Acid (OCA), when given as a single dose and multiple doses, is tolerated in children who have biliary atresia and to look at the effects that the study drug has on the body including an optional long-term extension.

A.3.2

Name or abbreviated title of the trial where available

ObetiCholic Acid in Pediatric Subjects with BiliaRy AtrEsia (CARE)

A.4.1

Sponsor's protocol code number

747-206

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/041/2021

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Intercept Pharmaceuticals, Inc.
B.1.3.4	Country	United States
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	Intercept Pharmaceuticals, Inc
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Syneos Health UK Limited
B.5.2	Functional name of contact point	Project Management
B.5.3	Address:
B.5.3.1	Street Address	Farnborough Business Park, 1 Pinehurst Road
B.5.3.2	Town/ city	Farnborough
B.5.3.3	Post code	GU14 7BF
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	390296199248
B.5.6	E-mail	Simona.Ripamonti@syneoshealth.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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	OCA 1.5mg
D.3.2	Product code	OCA
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
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	obeticholic acid
D.3.9.1	CAS number	459789-99-2
D.3.9.2	Current sponsor code	OCA
D.3.9.4	EV Substance Code	SUB91981
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1.5
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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	Yes
D.2.1.1.1	Trade name	Ocaliva
D.2.1.1.2	Name of the Marketing Authorisation holder	Intercept Pharma Ltd
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	OCA 5mg
D.3.2	Product code	OCA
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
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	obeticholic acid
D.3.9.1	CAS number	459789-99-2
D.3.9.2	Current sponsor code	OCA
D.3.9.4	EV Substance Code	SUB91981
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	OCA 0.1 mg
D.3.2	Product code	OCA
D.3.4	Pharmaceutical form	Tablet
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	obeticholic acid
D.3.9.1	CAS number	459789-99-2
D.3.9.2	Current sponsor code	OCA
D.3.9.3	Other descriptive name	OBETICHOLIC ACID
D.3.9.4	EV Substance Code	SUB91981
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.1
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
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	Tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 3
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
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

E.1.1.1

Medical condition in easily understood language

A rare disease of the liver and bile ducts that causes the bile to be trapped inside the liver

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

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.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10004654
E.1.2	Term	Biliary atresia, congenital
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

- Safety and tolerability
- Pharmacokinetics (PK) of OCA and its conjugates
oSingle dose (SD) PK Phase: To assess the PK of OCA and its conjugates after a single low dose of OCA on Day1 and determine subject eligibility for the Multiple-Dose (MD) Phase
oMultiple dose (MD) Phase: To assess the steady-state PK of OCA and its conjugates for a range of OCA doses

E.2.2

Secondary objectives of the trial

- Pharmacodynamics (PD) of OCA as measured by markers of farnesoid X receptor (FXR) activation and biomarkers of hepatobiliary function

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female pediatric subjects, aged ≥2 to <18 years old
2. Diagnosis of biliary atresia
3. Demonstrated successful HPE (also known as a Kasai portoenterostomy) as defined by total bilirubin <2 mg/dL (34.2 μmol/L) at least 3 months post-HPE procedure.
4. Able to swallow tablets (ie, tablet or mini-tablet formulation)

Please refer to the protocol for the entire list of inclusion criteria.

E.4

Principal exclusion criteria

1.Prior liver transplant or active status on transplant list
2.Conjugated (direct) bilirubin ≥ULN of site specific reference range
3.If conjugated bilirubin is not available: total bilirubin ≥2 mg/dL (34.2 μmol/L)
4.Platelets <150,000/μL
5.INR ≥1.5
6.Current or history of complications of decompensated chronic liver disease including:
a)High-risk gastroesophageal varices and/or varcieal bleeding
b)Clinically evident ascites related to portal hypertension
c)Hepatic encephalopathy
d)Prior placement of portosystemic shunt
e)Hepatopulmonary syndrome or portopulmonary hypertension
f)Hepatorenal syndrome
7.Current intractable pruritus or those requires systemic treatment for pruritus within 3 months of Screening (eg, with bile acid sequestrants or rifampicin)
8.Height and weight Z-score <-2 per WHO criteria
9.Acholic (pale) stools
10.AST >4x ULN
11.ALT > 4X ULN
12.GGT > 500 U/L
13.Anticoagulation therapy
14.Albumin < 3.5 g/Dl
15.Ongoing current cholangitis
16.Choledochal cystic disease
17.Renal disease defined as serum creatinine >ULN for subject's age, prior to enrollment

Please refer to the protocol for the entire list of exclusion criteria.

E.5 End points

E.5.1

Primary end point(s)

Safety and tolerability
- Treatment-emergent adverse events (TEAEs) including serious AEs (SAEs), electrocardiogram (ECG), physical exam, clinical laboratory results, vital signs.

PK
- Plasma concentrations of unconjugated OCA, its conjugates (glycine conjugate of OCA [glyco-OCA] and taurine conjugate of OCA [tauro-OCA]) and total OCA in the SD and MD Phases.

E.5.1.1

Timepoint(s) of evaluation of this end point

Safety and tolerability
- TEAEs taken in all visits, from Screening to end of study
- ECG taken at screening, day 57, week 4 of follow up (F/U) period, and ET visit.
- Physical exam taken at screening, day -1, 7, 21, 28, 42, 56, week 4 of F/U period, and ET visit
- Clinical laboratory results at screening, day 1, 2, 7, 21, 35, 42, 56, week 4 of F/U period, and ET visit
- Vital signs performed in all visits, from Screening to End of study
PK
PK sampling on days 1, 2 and 7 in SD phase; day 42, 56 and 57 in MD phase.

E.5.2

Secondary end point(s)

PD: Biomarkers of hepatobiliary function
-Alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), total and direct (conjugated) bilirubin, prothrombin time, INR, albumin, platelet count.

PD: Markers of FXR activation
-Fibroblast growth factor (FGF-19), 7-hydroxy-4-cholesten-3-one (C4), and endogenous bile acids.

E.5.2.1

Timepoint(s) of evaluation of this end point

PD: Biomarkers of hepatobiliary function indices
-ALP, AST, ALT, GGT, total and direct (conjugated) bilirubin, prothrombin time, INR, albumin, platelet count, taken at screening, day 1, 2, 7, 21, 35, 42, 56, week 4 of F/U period, and ET visit.

PD: Markers of FXR activation
-FGF-19, C4, and endogenous bile acids taken at day 1, 56, and ET visit.

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

Yes

E.6.7

Pharmacodynamic

Yes

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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)

E.8.2.2

Placebo

E.8.2.3

Other

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

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

Belgium

Germany

Netherlands

Poland

United Kingdom

France

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

LVLS

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

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)

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

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

Yes

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

All of the patients in this trial are children younger than 18 years.

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

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)

Standard care for biliary atresia

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

2022-04-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-04-25

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2023-03-09

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