Clinical Trials Register

Summary
EudraCT Number:	2013-001163-24
Sponsor's Protocol Code Number:	GB28547
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-08-28
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Germany - PEI

A.2

EudraCT number

2013-001163-24

A.3

Full title of the trial

A PHASE II, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, STUDY TO ASSESS THE EFFICACY AND SAFETY OF LEBRIKIZUMAB IN PATIENTS WITH IDIOPATHIC PULMONARY FIBROSIS.

A.3.1

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

A Study of Lebrikizumab in Patients With Idiopathic Pulmonary Fibrosis.

A.4.1

Sponsor's protocol code number

GB28547

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01872689

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	F. Hoffmann-La Roche Ltd
B.1.3.4	Country	Switzerland
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	F. Hoffmann-La Roche Ltd
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	F. Hoffmann-La Roche Ltd
B.5.2	Functional name of contact point	Trial Information Support Line-TISL
B.5.3	Address:
B.5.3.1	Street Address	Grenzacherstrasse 124
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4070
B.5.3.4	Country	Switzerland
B.5.6	E-mail	global.rochegenentechtrials@roche.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	lebrikizumab
D.3.2	Product code	RO5490255/F01-02
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
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	LEBRIKIZUMAB
D.3.9.2	Current sponsor code	RO5490255
D.3.9.3	Other descriptive name	TNX-650, rhuMAb anti-IL13, aIL-13, MILR1444A
D.3.9.4	EV Substance Code	SUB31913
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	125
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	lebrikizumab is a humanized monoclonal IgG4 antibody with an Fc region modification for increased stability, that binds specifically to soluble interleukin-13 (IL-13).
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	Yes
D.2.1.1.1	Trade name	ESBRIET
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration Limited
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.3.4	Pharmaceutical form	Capsule, hard
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	PIRFENIDONE
D.3.9.1	CAS number	53179-13-8
D.3.9.2	Current sponsor code	RO0220912
D.3.9.4	EV Substance Code	SUB09907MIG
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	267
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	Solution for injection in pre-filled syringe
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

IDIOPATHIC PULMONARY FIBROSIS

E.1.1.1

Medical condition in easily understood language

IDIOPATHIC PULMONARY FIBROSIS

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

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 lebrikizumab compared with placebo as monotherapy or as combination therapy with pirfenidone background compared with placebo in patients with IPF, as measured by the annualized rate of decline in percent predicted forced vital capacity (FVC) over 52 weeks.

E.2.2

Secondary objectives of the trial

•To evaluate lebrikizumab compared with placebo as monotherapy or as combination therapy with pirfenidone background therapy compared with placebo in patients with IPF as measured by:
o Efficacy on the basis of progression free survival (PFS), pulmonary function, diffusion capacity, non elective hospitalization for any cause, acute IPF exacerbation, proportion of patients with at least 10% decline in percentage of predicted FVC or death, and all cause death
o The distance walked in 6 minutes and health-related quality of life questionnaires
•To evaluate the safety of lebrikizumab as monotherapy compared with placebo in patients with IPF
•To evaluate the safety of lebrikizumab with pirfenidone as background therapy compared with placebo with pirfenidone as background therapy
in patients with IPF

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Adult patient, >/= 40 years of age
- Have a diagnosis of IPF according to the 2011 ATS/ERS/JRS/ALAT consensus statement on IPF within the previous 5 years from time of screening and confirmed at baseline
- Forced vital capacity (FVC) >/= 40% and </=100% predicted at screening
- Stable baseline lung function as evidenced by a difference of < 10% in FVC (L) measurements between screening and Day 1, Visit 2 prior to randomization
- Diffusion capacity of the lung for carbon monoxide >/= 25% and </= 90% predicted at screening
- Ability to walk >/= 100 meters unassisted in 6 minutes.
- Cohort A (monotherapy): No background IPF therapy for >=4 weeks allowed prior to randomization and throughout the placebo controlled
study period
- Cohort B (combination therapy): Tolerated dose of pirfenidone <=2403 milligrams/once daily (mg/QD) for >=4 weeks required prior to randomization and throughout the placebo controlled study period

E.4

Principal exclusion criteria

- History of severe allergic reaction or anaphylactic reaction to a biologic
agent or known hypersensitivity to any component of the lebrikizumab
injection
- Evidence of other known causes of interstitial lung disease (ILD)
- Lung transplant expected within 12 months of screening
- Evidence of clinically significant lung disease other than IPF
- Post bronchodilator forced expiratory volume in 1 second (FEV1)/FVC
ratio < 0.7 at screening
- Positive bronchodilator response, evidenced by an increase of >/=
12% predicted and 200 mL increase in FEV1 or FVC
- Class IV New York Heart Association chronic heart failure or historical
evidence of left ventricular ejection fraction < 35%
- Hospitalization due to an exacerbation of IPF within 4 weeks prior to or
during screening
- Known current malignancy or current evaluation for potential
malignancy
- An active upper or lower respiratory tract infection occurring at any
time within the screening period prior to the randomization visit
- Listeria monocytogenes infection or active parasitic infections within 6
months prior to Day 1, Visit 2.
- Active tuberculosis requiring treatment within 12 months of screening
- Known immunodeficiency, including but not limited to HIV infection
- Past use of any anti-IL-13 or anti-IL-14/IL-13 therapy, including
lebrikizumab
- Evidence of acute or chronic hepatitis or known liver cirrhosis
- Chronic treatment with pirfenidone within 4 weeks or five half lives
prior to screening (whichever is longer) to the end of the placebocontrolled
period (Day 365/Visit 16) (limited to Cohort A)
- For Cohort B: Known achalasia, esophageal stricture, or esophageal
dysfunction sufficient to limit the ability to swallow oral medication;
Tobacco smoking or use of tobacco-related products within 3 months of
screening or unwillingness to avoid smoking throughout the study; any
condition that, as assessed by the investigator, might be significantly
exacerbated by the known side effects associated with pirfenidone;
known or suspected peptic ulcer; use of strong CYP1A2 inhibitors (eg,
fluvoxamine or enoxacin) or moderate CYP1A2 inducers (limited to
tobacco smoking and tobacco related products) within 4 weeks of
randomization or during the study

E.5 End points

E.5.1

Primary end point(s)

Annualized rate of decrease in percent predicted FVC over 52 weeks (% FVC/year)

E.5.1.1

Timepoint(s) of evaluation of this end point

Up to Week 52

E.5.2

Secondary end point(s)

1. Progression-free survival
2. Annualized rate of decrease in pulmonary function (FVC) over a 52 week period (mL/year)
3. Time from randomization to first occurrence of a of >= 10% absolute decline in percent predicted FVC or death from any cause
4. Annualized rate of decrease in percent predicted in diffusion capacity of the lung for carbon monoxide over 52 weeks
5. Annualized rate of decrease in ATAQ IPF total score over a 52 week period
6. Time from randomization to non-elective hospitalization or death from any cause
7. Annualized rate of decline in six minute walk test distance over 52 weeks
8. Time from randomization to first event of acute IPF exacerbation
9. Time from randomization to first occurrence of the St. George's Respiratory Questionnaire (SGRQ) worsening
10. Safety: Incidence of adverse events

E.5.2.1

Timepoint(s) of evaluation of this end point

1-9. Up to Week 52
10. Up to 2.9 years

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)

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

Yes

E.8.1.7.1

Other trial design description

pirfenidone titration run-in period for cohort B/ combination therapy

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

Belgium

Canada

France

Germany

Italy

Japan

Mexico

Peru

Poland

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

'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:

105

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

372

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

155

F.4.2.2

In the whole clinical trial

480

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)

The Sponsor will offer post-study access to the study drug lebrikizumab and/or pirfenidone free of charge to eligible patients in accordance with the Roche Global Policy on Continued Access to Investigational Medicinal Product.

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

2013-09-05

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-11-04

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-09-13

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