Clinical Trials Register

Summary
EudraCT Number:	2014-004693-42
Sponsor's Protocol Code Number:	747-206
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2015-09-09
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

Netherlands - Competent Authority

A.2

EudraCT number

2014-004693-42

A.3

Full title of the trial

A Multicenter, Randomized, Open Label, Single- and Multiple-Dose, Dose Finding Study and Open-Label Extension to Assess the Effects 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.

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/175/2014

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	Wainwright Associates Limited
B.5.2	Functional name of contact point	Associate Director, RA
B.5.3	Address:
B.5.3.1	Street Address	Wessex House, Marlow Road
B.5.3.2	Town/ city	Bourne End
B.5.3.3	Post code	SL8 5SP
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	4401628530554
B.5.6	E-mail	enquiries@wainwrightassociates.co.uk

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	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 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.8 Information on Placebo

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

liver condition with abnormal bile flow

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	18.0
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	18.0
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

Single-Dose, Multiple-Dose (SD MD) Phase
To assess the effects of OCA in eligible pediatric subjects with biliary atresia on:
•Safety and tolerability
•PK of OCA and its conjugates

Open-Label Extension (OLE)
To assess the effects of long-term OCA treatment in eligible pediatric subjects with biliary atresia on:
•Long-term safety and tolerability

E.2.2

Secondary objectives of the trial

Single-Dose, Multiple-Dose (SD MD) Phase
To assess the effects of OCA in eligible pediatric subjects with biliary atresia on:
•Efficacy of OCA as measured by hepatobiliary indices of liver function
•PD of OCA as measured by appropriate biomarkers
•Exposure-response (PK/PD) and exposure-tolerability relationships

Open-Label Extension (OLE)
To assess the effects of long-term OCA treatment in eligible pediatric subjects with biliary atresia on:
•Durability of efficacy as measured by hepatobiliary indices of liver function
•PK, PD as measured by appropriate biomarkers

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Male or female pediatric subjects, aged <18 years
2.Diagnosis of biliary atresia, with successful HPE (also known as Kasai portoenterostomy) as defined by total bilirubin <2 mg/dL (34.2 μmol/L) at least 3 months post-HPE procedure.
3.Gamma-glutamyl transferase (GGT) ≥2x ULN
4.Able to take medications orally (ie, prior to the availability of the suspension formulation, able to swallow tablet(s) whole)
5.Prior to the availability of the suspension formulation, this study will initially restrict subject enrollment by weight into the 3 OCA dose groups as follows (ie, subjects must meet these restrictions at Screening and Day 0):
- Low Dose Group: ≥42 kg
- Medium Dose Group: ≥20 kg
- High Dose Group: ≥21 kg

E.4

Principal exclusion criteria

Subjects with or experiencing:
1. Prior liver transplant or active status on transplant list
2.Complications of decompensated cirrhosis including:
a. Total bilirubin ≥2 mg/dL (34.2 μmol/L)
b. Platelets <40,000/µL
c. INR ≥2
d. Presence of known or large esophageal varices
e. Uncontrolled ascites (diuretic resistant)
f. Prior placement of portosystemic shunt
g. Diagnosis of hepatopulmonary syndrome or portopulmonary hypertension
3.Current intractable pruritus or those requiring systemic treatment for pruritus within 3 months (eg, with bile acid sequestrants or rifampicin)

E.5 End points

E.5.1

Primary end point(s)

SAFETY. Adverse events and laboratory values

PK. Plasma concentrations of OCA and its conjugates (glycine 6α-ethyl-chenodeoxycholic acid [glyco-OCA] and taurine 6α-ethyl-chenodeoxycholic acid [tauro-OCA]) after single- and multiple-doses

E.5.1.1

Timepoint(s) of evaluation of this end point

PK sampling on days 1, 2, 7, 42, 63, and 64 in the single dose and multi dose phases.

E.5.2

Secondary end point(s)

EFFICACY. Alkaline phosphatase [ALP], aspartate aminotransferase [AST], alanine aminotransferase [ALT], gamma-glutamyl transferase [GGT], total and conjugated bilirubin, albumin, and international normalized ratio [INR]).

PD. 7-hydroxy-4-cholesten-3-one [C4], and endogenous bile acids.

PK/PD. Relationship of total OCA exposure to PD parameters, efficacy measures, Child-Pugh Score and adverse events

E.5.2.1

Timepoint(s) of evaluation of this end point

C4 and endogenous bile acids taken on Days 1, 42 and 63.

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

Yes

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

Yes

E.8.1.1

Randomised

Yes

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

Yes

E.8.2.3.1

Comparator description

standard care

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the 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

Canada

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

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)

Information not present in EudraCT

F.1.1.4

Infants and toddlers (28 days-23 months)

Yes

F.1.1.4.1

Number of subjects for this age range:

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

2015-08-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-01-05

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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