Clinical Trials Register

Summary
EudraCT Number:	2019-001015-23
Sponsor's Protocol Code Number:	APHP180668
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2020-06-04
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

France - ANSM

A.2

EudraCT number

2019-001015-23

A.3

Full title of the trial

Double blind, multicentric, randomized, placebo-controlled trial, evaluating the efficacy of 24-month of bezafibrate in primary sclerosing cholangitis with persistent cholestasis despite ursodeoxycholic acid therapy

A.3.1

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

Study evaluating the efficacy of bezafibrate for people suffering of primary sclerosing cholangitis

A.3.2

Name or abbreviated title of the trial where available

BEZASCLER

A.4.1

Sponsor's protocol code number

APHP180668

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	ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Ministère de la santé
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)
B.5.2	Functional name of contact point	Sophie COURTIAL-DESTEMBERT
B.5.3	Address:
B.5.3.1	Street Address	DRCI Hôpital St Louis, 1 av. Claude Vellefaux
B.5.3.2	Town/ city	Paris
B.5.3.3	Post code	75010
B.5.3.4	Country	France
B.5.4	Telephone number	+33140275591
B.5.5	Fax number	+33144841701
B.5.6	E-mail	sophie.courtial-destembert@aphp.fr

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	BEFIZAL L.P. 400 mg, comprimé enrobé à libération prolongée
D.2.1.1.2	Name of the Marketing Authorisation holder	ARROW GENERIQUES
D.2.1.2	Country which granted the Marketing Authorisation	France
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	C10AB02
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.3.9.4	EV Substance Code	SUB05810MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/g milligram(s)/gram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	400
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

Adult patients with primary sclerosing cholangitis

E.1.1.1

Medical condition in easily understood language

Primary sclerosing cholangitis

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

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

To assess the efficacy of 24-month treatment with bezafibrate (400 mg SR/d) versus placebo in addition to standard UDCA therapy in primary sclerosing cholangitis

E.2.2

Secondary objectives of the trial

1. To compare between groups:
a) Components of the primary composite outcome at M24
b) Adverse effects including IBD activity hepatic, muscular, and kidney
function.
c) Quality of life and scores for pruritus and fatigue at M12 and M24
d) Changes in liver tests between M0 and M24
e) Occurrence of clinical events and transplant-free survival
2. Exploratory objectives:
- Changes in serum markers of fibrosis (ELF score and Pro-C3) and
cholangiographic abnormalities between M0 and M24
- Course of biomarkers (including microbiota) and correlation with
observed effects between M0 and M24
- Need for endoscopic procedures between M0 and M24

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Males or females ≥ 18 and ≤ 75 years
• Large duct PSC verified by retrograde, operative, percutaneous or
magnetic resonance cholangiography (MRC) demonstrating intrahepatic
and /or extrahepatic biliary duct changes consistent with PSC
• Colonoscopy within the last 5 years (or within 3 months if IBD is
associated to PSC) with no cancer nor all-grade dysplasia
• ALP ≥ 1.5 ULN at baseline
• Treatment with UDCA (15-20 mg/kg/d) for ≥ 6 months before
inclusion.
• Using
contraceptive in women of childbearing potential. Women of childbearing potential, i.e. fertile, following menarche and until becoming post-menopaused unless permanently sterile, who are sexually active have to apply a highly effective method of birth control with a low failure rate (i.e., less than 1% per year) when used constantly and correctly.
• Affiliation to a social security system (AME excepted)
• Signed informed consent

E.4

Principal exclusion criteria

• Child-Pugh score B or C
• Ascites or digestive hemorrhage (or history of)
• Total bilirubin in the last 3 months > 50 μmole/L (3 mg/dl)
• Gilbert syndrome defined as unconjugated bilirubinemia > 12 μmol/L
• Albumin in the last 3 months < 35 g/L
• Prothrombin index in the last 3 months < 70%
• Platelets count in the last 3 months < 100000/mm3
• ALT or AST > 5 ULN in the last 3 months
• Prior liver transplantation
• Treatment with a fibrate within the last 3 months inclusion or with a
statin at inclusion

E.5 End points

E.5.1

Primary end point(s)

Proportion of patients with serum Alkaline Phosphatase < 1.5 ULN and a reduction of at least 15% from baseline at M24 and normal serum bilirubin and no increase of liver stiffness at M24 compared to Baseline (delta M24–M0 ≤ 0).

E.5.1.1

Timepoint(s) of evaluation of this end point

24 months

E.5.2

Secondary end point(s)

1. To compare between groups
a) Components of the primary composite outcome analyzed separately:
Proportion of patients with:
• serum Alkaline Phosphatase < 1.5 ULN at M24 and at least 15% of
decrease from baseline at M24
• complete normalization of s-ALP at M24 (s-ALP ≤ 1.0 ULN at M24)
• normal serum bilirubin
• no increase in liver stiffness at M24
b) Safety endpoint: Percentage of patients with clinical (including
increased IBD activity) or biological adverse events (elevated creatinine,
ALT, AST or CPK) during the study period;
c) Quality of life (QMCF questionnaire – Questionnaire de la maladie
chronique du foie) and scores for pruritus (measured by VAS and 5D
pruritus scale) and fatigue (measured by adapted PBC-40 questionnaire
(M0, M12 and M24))
d) Changes in Patient-Reported Outcomes (PRO) specific for PSC (45).
e) Changes in biochemical liver tests other than ALP, including total and
conjugated bilirubin, GGT, AST, ALT, albumin, and INR, and in platelet
count. Changes in total cholesterol, LDL, HDL and triglycerides.
f) Survival rate without liver transplantation or hepatic events (ascites,
variceal bleeding, encephalopathy, acute cholangitis,
cholangiocarcinoma, hepatocellular carcinoma or serum total bilirubin >
100 μmol/L for at least 3 months). PSC Prognostic scores including the
MELD score, the Revised PSC Mayo Risk Score, the Hannover Score and
the Amsterdam-Oxford prognostic model (M0, M12, M24)
2. Exploratory endpoints (M0, M12, M24)
• Course of:
- serum markers of liver fibrosis (ELF score and Pro-C3)
- cholangiographic abnormalities
- biological markers of liver function
- bile acids and cytokines
- microbiota (M0-M12-M24) (dietetary questionnaire and questionnaire
accompanying the stool sample)
• Need for endoscopic treatment of biliary strictures

E.5.2.1

Timepoint(s) of evaluation of this end point

24 months

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

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

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

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

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

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

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

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

104

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

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	French Network of Reference and Competence
G.4.3.4	Network Country	France

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-05-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-04-02

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

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials