Clinical Trials Register

Summary
EudraCT Number:	2017-000474-11
Sponsor's Protocol Code Number:	747-304
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2018-04-20
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

Spain - AEMPS

A.2

EudraCT number

2017-000474-11

A.3

Full title of the trial

A Phase 3, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Obeticholic Acid in Subjects with Compensated Cirrhosis due to Nonalcoholic Steatohepatitis.

Estudio de fase 3, doble ciego, aleatorizado, controlado con placebo, multicéntrico para evaluar la eficacia y la seguridad del ácido obeticólico en pacientes con cirrosis compensada debida a esteatohepatitis no alcohólica.

A.3.1

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

A clinical trial where neither the doctor, patient or sponsor know whether a placebo or active medicine is being given to the patient with compensated cirrhosis due to nonalcoholic steatohepatitis to see if the medicine is effective and safe in the treatment of that disease

Un ensayo clínico en el que ni el medico, ni el paciente ni el promotor saben si se le proporciona placebo o medicina activa al paciente con cirrosis compensada debida a esteatohepatitis no alcohólica para ver si la medicina es efectiva y segura en el tratamiento de esta enfermedad.

A.3.2

Name or abbreviated title of the trial where available

REVERSE

A.4.1

Sponsor's protocol code number

747-304

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	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	INC Research
B.5.2	Functional name of contact point	Nichole Godding
B.5.3	Address:
B.5.3.1	Street Address	4 Fleming Buidling, Edinburgh Technopole
B.5.3.2	Town/ city	Milton Brudge, Midlothian
B.5.3.3	Post code	EH26 0BE
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	0034916307447
B.5.6	E-mail	nichole.godding@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	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	Obeticholic Acid
D.3.2	Product code	INT-747, 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	6-ECDCA
D.3.9.3	Other descriptive name	6 alpha-ethylchenodeoxycholic acid (6-EDCA), OCA, INT-747
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	10
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	Obeticholic Acid
D.3.2	Product code	INT-747, 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	6-ECDCA
D.3.9.3	Other descriptive name	6 alpha-ethylchenodeoxycholic acid (6-EDCA), OCA, INT-747
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	25
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Compensated Cirrhosis due to Nonalcoholic Steatohepatitis

Cirrosis compensada debida a esteatohepatitis no alcohólica

E.1.1.1

Medical condition in easily understood language

Compensated Cirrhosis due to Nonalcoholic Steatohepatitis

Cirrosis compensada debida a esteatohepatitis no alcohólica

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the effects of OCA treatment compared with placebo on improvement in fibrosis by at least 1 stage with no worsening of Nonalcoholic Steatohepatitis (NASH), using the NASH Clinical Research Network (CRN) scoring system.

Evaluar los efectos del tratamiento con AOC en comparación con placebo en la mejoría de la fibrosis en al menos 1 estadio sin empeoramiento de la esteatohepatitis no alcohólica (EHNA), usando el sistema de puntuación de la Red de Investigación Clínica (Clinical Research Network, CRN).

E.2.2

Secondary objectives of the trial

To evaluate the effects of OCA treatment compared with placebo on improvement in fibrosis by at least 2 stages using Ishak scoring criteria and resolution of NASH using the NASH CRN scoring system.

Evaluar los efectos del tratamiento con AOC en comparación con placebo en la mejoría de la fibrosis en al menos 2 estadios mediante los criterios de puntuación de Ishak y la resolución de la EHNA usando el sistema de puntuación de CRN.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Subjects with a confirmed diagnosis of NASH and a fibrosis score of 4 based upon the NASH CRN scoring system determined by central reading.

Pacientes con un diagnóstico confirmado de EHNA y una puntuación de fibrosis de 4 en base al sistema de puntuación de la CRN para la EHNA determinado por lectura central.

E.4

Principal exclusion criteria

1. Current or past history of hepatic decompensation such as clinically significant ascites, hepatic encephalopathy (HE), or variceal bleeding.
2. Current or past history of CP score >=7 points
3. MELD score >12
4. ALT >=5× ULN
5. Calculated creatinine clearance <60 mL/min using Cockcroft-Gault method
6. Hemoglobin A1c >=9.5%
7. Evidence of other known forms of chronic liver disease such as alcoholic liver disease, hepatitis B, hepatitis C, PBC, PSC, autoimmune hepatitis, Wilson disease, iron overload, Alpha-1-antitrypsin deficiency, drug-induced liver injury, Known or suspected HCC
8. History of liver transplant, current placement on a liver transplant list

1. Antecedentes de descompensación hepática o descompensación hepática en la actualidad, tal como ascitis importante, encefalopatía hepática, sangrado de varices.
2. Antecedentes de trastorno de la función hepática o trastorno de la función hepática actual con una puntuación de CP >=7 puntos.
3. Puntuación de MELD > 12.
4. AST ≥5 veces el límite superior de la normalidad (LSN).
5. Aclaramiento de creatinina calculado < 60 ml/min mediante la fórmula de Cockcroft-Gault.
6. Hemoglobina A1c >= 9,5%
7. Evidencia de otras formas conocidas de enfermedad hepática crónica, incluidas enfermedad hepática alcohólica, hepatitis B, hepatitis C, cirrosis biliar primaria, colangitis esclerosante primaria, hepatitis autoinmunitaria, enfermedad de Wilson, sobrecarga de hierro, deficiencia en alfa-1-antitripsina, antecedentes de lesión hepática conocida inducida por medicamentos, sospecha o confirmación de CHC.

E.5 End points

E.5.1

Primary end point(s)

Improvement in fibrosis by at least 1 stage with no worsening of NASH, using NASH CRN scoring system.

Mejoría de la fibrosis en al menos 1 estadio sin empeoramiento de la EHNA usando el sistema de puntuación de la CRN para la EHNA

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline to Month 12

Desde la situación inicial hasta el mes 12.

E.5.2

Secondary end point(s)

Improvement in fibrosis by at least 2 stages using the Ishak scoring criteria and NASH resolution using the NASH CRN scoring

Mejoría de la fibrosis en al menos 2 estadios utilizando los criterios de puntuación de Ishak y el sistema de puntuación de la CRN para la EHNA

E.5.2.1

Timepoint(s) of evaluation of this end point

Baseline to Month 12

Desde la situación inicial hasta el mes 12.

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

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

Yes

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

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

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

Canada

France

Germany

New Zealand

Spain

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

Last Visit of Last Subject

Última visita del ultimo paciente

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

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)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

340

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

200

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

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

150

F.4.2.2

In the whole clinical trial

540

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)

Currently, there are no therapies approved for the treatment of NASH. Doctors may recommend lifestyle changes such as diet and exercise to help losing weight; and treatment of high blood pressure and diabetes, to try and prevent the disease from getting worse. Vitamin E or a thiazolidinedione/glitazone may also be recommended for patients with NASH who don’t have diabetes.

Actualmente no hay terapias aprobadas para el tratamiento de EHNA. Los médicos pueden recomendar cambios en el estilo de vida, tales como dieta y ejercicio para ayudar a bajar de peso; y tratamiento para presión arterial alta y diabetes, para intentar prevenir el empeoramiento de la enfermedad Vitamina E o thiazolidinedione/glitazona pueden ser también recomendados para pacientes con EHNA que no tienen diabetes.

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

2018-06-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-06-21

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

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