Clinical Trials Register

Summary
EudraCT Number:	2022-001241-20
Sponsor's Protocol Code Number:	747-214
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:	2022-09-14
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

2022-001241-20

A.3

Full title of the trial

A Phase 2a, Double-Blind, Randomized, Active Controlled, Parallel Group Study Evaluating the Efficacy, Safety, and Tolerability of Bezafibrate Administered in Combination with Obeticholic Acid in Subjects with Primary Biliary Cholangitis

Studio di fase 2a, in doppio cieco, randomizzato, con controllo attivo, a gruppi paralleli per valutare l'efficacia, la sicurezza e la tollerabilità del bezafibrato somministrato in combinazione con acido obeticolico in soggetti con colangite biliare primitiva

A.3.1

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

Study to determine if the investigational drug obeticholic acid (also known as OCA) in combination with the investigational drug bezafibrate (BZF), has an effect on Primary Biliary Cholangitis (also known as PBC).

Studio per determinare se il farmaco sperimentale acido obeticolico (noto anche come OCA) in combinazione con il farmaco sperimentale bezafibrato (BZF) ha un effetto sulla colangite biliare primitiva (nota anche come PBC).

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

747-214

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT05239468

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	Labcorp Drug Development Limited
B.5.2	Functional name of contact point	Global Regulatory Submissions
B.5.3	Address:
B.5.3.1	Street Address	Osprey House, Maidenhead Office Park, Westacott Way
B.5.3.2	Town/ city	Maidenhead
B.5.3.3	Post code	SL6 3QH
B.5.3.4	Country	United Kingdom
B.5.6	E-mail	submissions@labcorp.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 5mg
D.2.1.1.2	Name of the Marketing Authorisation holder	Intercept Pharma International 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	Yes
D.2.5.1	Orphan drug designation number	EU/3/10/753
D.3 Description of the IMP
D.3.1	Product name	Obeticholic Acid
D.3.2	Product code	[-]
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	ACIDO OBETICOLICO
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	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	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	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	Comparator
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	Bezafibrate
D.3.2	Product code	[-]
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	Bezafibrate
D.3.9.1	CAS number	41859-67-0
D.3.9.2	Current sponsor code	-
D.3.9.3	Other descriptive name	Bezafibrate, Beza, BZF, Bezalip
D.3.9.4	EV Substance Code	SUB05810MIG
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	100
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	Comparator
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	Bezafibrate
D.3.2	Product code	[-]
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	Bezafibrate
D.3.9.1	CAS number	41859-67-0
D.3.9.2	Current sponsor code	-
D.3.9.3	Other descriptive name	Bezafibrate, Beza, BZF, Bezalip
D.3.9.4	EV Substance Code	SUB05810MIG
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	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	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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Primary Biliary Cholangitis

Colangite biliare primitiva

E.1.1.1

Medical condition in easily understood language

Primary Biliary Cholangitis

Colangite biliare primitiva

E.1.1.2

Therapeutic area

Body processes [G] - Digestive System and Oral Physiological Phenomena [G10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	PT
E.1.2	Classification code	10080429
E.1.2	Term	Primary biliary cholangitis
E.1.2	System Organ Class	10019805 - Hepatobiliary disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective is to assess the effects of the combination of OCA and BZF on alkaline phosphatase (ALP) in comparison to BZF alone in subjects with PBC

L'obiettivo primario è quello di valutare gli effetti della combinazione di OCA più BZF sulla fosfatasi alcalina (ALP) rispetto al solo BZF in soggetti con colangite biliare primitiva (PBC)

E.2.2

Secondary objectives of the trial

The secondary objectives are to assess the effects of the combination of OCA plus BZF versus BZF alone in subjects with PBC on the following:
• Biochemical disease markers, including ALP, GGT, ALT, AST, total and conjugated bilirubin, and lipid panel
• Biomarkers of bile acid synthesis and homeostasis, including 7a-hydroxy-4-cholesten-3-one (C4) and bile acids
• Safety and tolerability

Gli obiettivi secondari sono atti a valutare gli effetti della combinazione di OCA più BZF rispetto a BZF da solo in soggetti con PBC su quanto segue:
• Marcatori biochimici della malattia, inclusi ALP, GGT, alanina aminotransferasi (ALT), aspartato aminotransferasi (AST), bilirubina totale e coniugata e pannello lipidico
• Biomarcatori della sintesi e dell'omeostasi degli acidi biliari, inclusi 7a-idrossi-4 colesteno-3-one (C4) e acidi biliari
• Sicurezza e tollerabilità

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. A define or probable diagnosis of PBC
2. Qualifying ALP and/or bilirubin liver biochemistry values
3. Taking ursodeoxycholic acid (UDCA) for at least 12 months or no UDCA for 3 months before Day 1

1. Una diagnosi certa o probabile di PBC
2. Valori biochimici qualificanti di fosfatasi alcalina e/o bilirubina
3. Assunziona di acido ursodesossicolico (UDCA) per almeno 12 mesi o senza UDCA per 3 mesi prima del Giorno 1

E.4

Principal exclusion criteria

1. History or presence of other concomitant liver diseases
2. Presence of clinical complications of PBC
3. History or presence of decompensating events
4. Current or history of gallbladder disease
5. If female, known pregnancy, or has a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating
6. Treatment with commercially available OCA or participation in a previous study involving OCA within 3 months before Screening
7. Treatment with commercially available fibrates, or participation in a previous study involving fibrate within 3 months before Screening

1. Anamnesi o presenza di altre malattie epatiche concomitanti
2. Presenza di complicanze cliniche della PBC
3. Anamnesi o presenza di eventi scompensanti
4. Malattie della cistifellea passate o in corso
5. Nei soggetti di sesso femminile, gravidanza nota o test di gravidanza sulle urine positivo (confermato da test di gravidanza su siero positivo), o allattamento
6. Trattamento con OCA disponibile in commercio o partecipazione a uno studio precedente con OCA nei 3 mesi precedenti lo screening
7. Trattamento con fibrati disponibili in commercio, o partecipazione a uno studio precedente con fibrati nei 3 mesi precedenti lo screening

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy endpoint is the change in ALP from baseline to Week 12 in the DB Phase.

L'endpoint primario di efficacia è la variazione di fosfatasi alcalina (ALP) dal basale alla Settimana 12 nella fase di trattamento in doppio cieco (DB phase).

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline to Week 12

Dal basale alla Settimana 12

E.5.2

Secondary end point(s)

- Safety and tolerability
- The response rates of >=10%, >=20%, >=30%, and >=40% reduction from baseline at Week 12, and normalization rates of ALP at Week 12
- Normalization rates at Week 12 of GGT, ALT, AST, total and conjugated bilirubin, and lipid panel
- Change from baseline to Week 12 in GGT, ALT, AST, and total and conjugated bilirubin, and lipid panel
- Change from baseline to Week 12 in 7a-hydroxy-4-cholesten-3-one (C4) and bile acids

- Sicurezza e tollerabilità
- I tassi di risposta di ALP di >=10%, >=20%, >=30%, e >=40% di riduzione rispetto al basale alla Settimana 12, e i tassi di normalizzazione di ALP alla settimana 12
- I tassi di normalizzazione alla Settimana 12 di GGT, ALT, AST, bilirubina totale e coniugata e pannello lipidico
- Variazione dal basale alla settimana 12 di GGT, ALT, AST, bilirubina totale e coniugata e pannello lipidico
- Varazione dal basale alla settimana 12 di 7a-idrossi-4 colesteno-3-one (C4) e acidi biliari

E.5.2.1

Timepoint(s) of evaluation of this end point

Baseline to end of study

Dal basale fino alla fine dello studio

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

Yes

E.6.11

Pharmacogenomic

Yes

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

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)

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

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

Argentina

Canada

United States

Turkey

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

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

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:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

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)

None

Nessuno

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

2022-11-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-10-20

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

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