Clinical Trials Register

Summary
EudraCT Number:	2011-000554-31
Sponsor's Protocol Code Number:	CNTO1275PBC2001
National Competent Authority:	Sweden - MPA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-08-16
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

Sweden - MPA

A.2

EudraCT number

2011-000554-31

A.3

Full title of the trial

A Phase 2, Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel-group Study Evaluating the Efficacy and Safety of Ustekinumab in Subjects with Primary Biliary Cirrhosis Who had an Inadequate Response to Ursodeoxycholic Acid (UDCA)

A.3.1

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

A Study of Efficacy and Safety of Ustekinumab in Patients with Primary Biliary Cirrhosis (PBC) Who had an Inadequate Response to Ursodeoxycholic Acid

A.3.2

Name or abbreviated title of the trial where available

PURIFI

A.4.1

Sponsor's protocol code number

CNTO1275PBC2001

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	Janssen-Cilag International N.V.
B.1.3.4	Country	Belgium
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	Janssen Research & Development, a division of JJPRD, LLC
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	Janssen-Cilag International N.V.
B.5.2	Functional name of contact point	Clinical Registry Group
B.5.3	Address:
B.5.3.1	Street Address	Archimedesweg 29
B.5.3.2	Town/ city	Leiden
B.5.3.3	Post code	2333 CM
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+31715242166
B.5.5	Fax number	+31715242110
B.5.6	E-mail	ClinicalTrialsEU@its.jnj.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	Ustekinumab
D.3.2	Product code	CNTO1275
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Ustekinumab
D.3.9.1	CAS number	815610-63-0
D.3.9.2	Current sponsor code	CNTO1275
D.3.9.3	Other descriptive name	N/A
D.3.9.4	EV Substance Code	SUB27761
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	90
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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	Yes
D.3.11.13.1	Other medicinal product type	Monoclonal Antibody

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	Solution for injection
D.8.4	Route of administration of the placebo	Subcutaneous 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 Cirrhosis

E.1.1.1

Medical condition in easily understood language

Primary Biliary Cirrhosis

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10036680
E.1.2	Term	Primary biliary cirrhosis
E.1.2	System Organ Class	100000004871

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

This is a Phase 2 study that is divided into 2 parts. Part 1 is an open-label, proof-of-concept study. Part 2 is a multi-center, randomized, double-blind, placebo-controlled, parallel-group study evaluating the efficacy and safety of ustekinumab in subjects with PBC who had an inadequate response to UDCA.

PART 1: Open Label
Primary Objectives:
• To evaluate the efficacy of ustekinumab in reducing alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin in subjects with PBC.
• To determine the ustekinumab regimen(s), based on safety and efficacy, for development in Part 2.

PART 2: Double-blind
Primary Objectives:
• To evaluate the efficacy of ustekinumab in achieving ALP response (a decrease from baseline of > 40% in ALP) in subjects with PBC who had an inadequate response to UCDA.
• To evaluate the safety of ustekinumab in subjects with PBC.

E.2.2

Secondary objectives of the trial

PART 2: Double-blind
Secondary Objectives:
• To evaluate the efficacy of ustekinumab in reducing ALP, ALT, AST, and total bilirubin.
• To evaluate improvement in liver fibrosis as measured by the Enhanced Liver Fibrosis (ELF) test.
• To evaluate improvement in liver histology as measured by the modified Hepatic Activity Index (HAI).
• To evaluate the efficacy of ustekinumab in reducing cholestasis as measured by serum bile acid concentrations.
• To evaluate pharmacokinetics, immune response (IR), and pharmacodynamics of ustekinumab.
• To evaluate ustekinumab in improving fatigue, pruritus, and quality of life.
• To evaluate the effect ustekinumab has on long-term disease progression (death, transplant, cirrhosis, doubling of bilirubin).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Have proven or are likely to have PBC; Be on a stable dose of ursodeoxycholic acid for at least 6 months prior to Week 0;Have screening ALP level > 1.67 ULN; Have screening laboratory test results within protocol-specified limits; Have no history of latent or active TB prior to screening and no signs or symptoms suggestive of active TB upon medical history and/or physical examination.

E.4

Principal exclusion criteria

Has history of gastrointestinal bleeding, secondary to portal hypertension, hepatic encephalopathy, or ascites requiring treatment with diuretics; Has a screening direct bilirubin > 1.0 mg/dL; Has a previous liver histology with a diagnosis of steatohepatitis or has a high risk of nonalcoholic steatohepatitis; Has a previous liver histology with a diagnosis of chronic autoimmune hepatitis or has a high risk of autoimmune hepatitis overlap syndrome; Testing positive for surface antigen (HBsAg+), regardless of the results of other hepatitis B tests; Have used colchicine, methotrexate (MTX), azathioprine (AZA), or systemic corticosteroids within 3 months prior to the first administration of study drug.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is ALP response at Week 28 as defined by a decrease from baseline of > 40% in ALP.

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 28

E.5.2

Secondary end point(s)

The major secondary endpoints by order of importance are:

1. Modified Corpechot Response at Week 28 as defined by ALP ≤ 3 x ULN, AST ≤ 2 x ULN, total bilirubin ≤ 1 mg/dL for subjects with a total bilirubin ≤ 1 mg/dL at baseline, and > 40% decrease from baseline in ALP. Subjects with total bilirubin >1 mg/dL at baseline will only be considered responders provided that the direct bilirubin value does not increase;

2. Change from baseline in ELF score at Week 28;

3. Change from baseline in the modified HAI at Week 28, in subjects with biopsies;

4. Change from baseline in the total serum bile acid concentrations at Week 28.

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 28

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

E.6.10

Pharmacogenetic

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)

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

Canada

France

Germany

Italy

Sweden

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

The study is considered completed with the last visit for the last subject participating in the study. The final data from the investigational site will be sent to the sponsor (or designee) after completion of the final subject visit at that site, in the time frame specified in the Clinical Trial Agreement.

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	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.2.1	Number of subjects for this age range:	96
F.1.3	Elderly (>=65 years)	Yes
F.1.3.1	Number of subjects for this age range:	32
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	6
F.4.2	For a multinational trial
F.4.2.1	In the EEA	42
F.4.2.2	In the whole clinical trial	128

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

2011-09-30

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-10-26

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-06-28

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