Clinical Trials Register

Summary
EudraCT Number:	2011-004218-41
Sponsor's Protocol Code Number:	GB27862
National Competent Authority:	Slovakia - SIDC (Slovak)
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-05-15
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

Slovakia - SIDC (Slovak)

A.2

EudraCT number

2011-004218-41

A.3

Full title of the trial

A Phase III, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of LEBRIKIZUMAB in patients with uncontrolled asthma who are on inhaled corticosteroids and second controller medication.

Fáza III randomizovanej, dvojito zaslepenej, placebom kontrolovanej štúdie na vyhodnotenie účinnosti a bezpečnosti lebrikizumabu u pacientov s nekontrolovanou astmou, ktorí užívajú inhalačné kortikosteroidy a druhý kontrolujúci liek

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

Lute

A.4.1

Sponsor's protocol code number

GB27862

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01545440

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/F01-01
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	lebrikizumab
D.3.9.1	CAS number	953400-68-5
D.3.9.2	Current sponsor code	RO5490255
D.3.9.3	Other descriptive name	TNX-650, rhuMAb anti-IL13, aIL-13, MILR1444A
D.3.10	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	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 mutated Fc 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	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
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.3.9.1	CAS number	953400-68-5
D.3.9.2	Current sponsor code	RO5490255
D.3.9.3	Other descriptive name	TNX-650, rhuMAb anti-IL13, aIL-13, MILR1444A
D.3.10	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	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 mutated Fc for increased stability that binds specifically to soluble interleukin-13 (IL-13).

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

Uncontrolled asthma despite the use of an inhaled corticosteroid
and a second controller medication.

E.1.1.1

Medical condition in easily understood language

Uncontrolled asthma despite daily therapy.

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10003553
E.1.2	Term	Asthma
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal 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 efficacy of lebrikizumab compared with placebo as measured by the rate of exacerbations
• The safety of lebrikizumab compared with placebo
• Periostin as a predictive biomarker (diagnostic)
• The efficacy and safety of different dose levels of lebrikizumab compared to placebo.

E.2.2

Secondary objectives of the trial

The efficacy of lebrikizumab compared with placebo with respect to lung function, time to first exacerbation, fractional exhaled nitric oxide (FeNO), asthma-specific health-related quality of life, rescue medication use (i.e. short-acting β-agonists [SABA]), and health care utilization.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

ECG SUBSTUDY version 2 dated 5 April 2012 - IN ASSOCIATION WITH LEBRIKIZUMAB STUDY GB27862: A PHASE III, RANDOMIZED, DOUBLE-BLIND, PLACEBOCONTROLLED STUDY TO ASSESS THE EFFICACY AND SAFETY OF LEBRIKIZUMAB IN PATIENTS WITH UNCONTROLLED ASTHMA WHO ARE ON INHALED CORTICOSTEROIDS AND A SECOND CONTROLLER MEDICATION.
The primary objective of this substudy is as follows:
• To evaluate the effect of lebrikizumab treatment on cardiac repolarization on the basis of prolongation of the QT interval in surface ECGs in patients with uncontrolled asthma.
The secondary objectives of this substudy are as follows:
• To evaluate the effect of lebrikizumab treatment on other ECG measures
• To assess the effect of lebrikizumab treatment on ECG morphology.

E.3

Principal inclusion criteria

- Ability and willingness to provide written informed consent and to comply with the study protocol
- 18–75 years old at screening
- Asthma diagnosis for ≥ 12 months prior to the start of screening
- Bronchodilator response (defined as a minimum 12% relative improvement in the volume of FEV1 after bronchodilator administration) during the screening period
- Pre-bronchodilator FEV1 40%–80% of predicted
- On ICS (500-2000 µg/day of fluticasone propionate DPI or equivalent, total daily dose) for ≥ 6 months prior to the start of screening
- On an eligible second controller medication for 6 months prior to the start of screening
- Uncontrolled asthma demonstrated during the screening period
- Chest X-ray or computed tomography (CT) scan obtained within 12 months prior to screening or chest X-ray during the screening period confirming the absence of other lung disease
- Demonstrated adherence with controller medication during the screening period.

E.4

Principal exclusion criteria

- History of a severe allergic reaction or anaphylactic reaction to a biologic agent
- Daily or alternate day oral corticosteroid maintenance therapy within the 3 months prior to screening
- Treatment with systemic corticosteroids within the 4 weeks prior to, or at anytime during the screening period
- Recent major episode of infection
- Active parasitic infection or Listeria monocytogenes infection within the 6 months prior to screening
- Active tuberculosis requiring treatment within the 12 months prior to screening
- Known immunodeficiency, including, but not limited to, HIV infection
- Evidence of acute or chronic hepatitis or known liver cirrhosis
- History of cystic fibrosis, chronic obstructive pulmonary disease, and/or other clinically significant lung disease other than asthma
- Known current malignancy or current evaluation for a potential malignancy
- Other clinically significant medical disease that is uncontrolled despite treatment or that is likely, in the opinion of the investigator, to require a change in therapy or impact the ability to participate in the study
- History of alcohol, drug, or chemical abuse
- Current smoker (cigarettes, pipe, cigar, or marijuana) or former smoker with a smoking history of > 10 pack-years
- Current use of an immunomodulatory/immunosuppressive therapy or past use within 3 months or 5 drug half-lives (whichever is longer) prior to screening
- Use of a biologic therapy including omalizumab (Xolair) at any time during the 6 months prior to screening
- Use of zileuton (ZYFLO) or roflumilast (Daxas, Daliresp) at any time during the 6 months prior to screening
- Treatment with an investigational agent within 30 days of screening (or 5 half lives of the investigational agent, whichever is longer)
- Receipt of a live/attenuated vaccine within the 4 weeks prior to sreening
- Female patients who are pregnant or lactating or unwilling to use a highly effective method of contraception
- Body mass index > 38 kg/m2
- Body weight < 40 kg.

E.5 End points

E.5.1

Primary end point(s)

Rate of asthma exacerbations.

E.5.1.1

Timepoint(s) of evaluation of this end point

52 weeks

E.5.2

Secondary end point(s)

• Frequency of adverse events during the 52-week placebo-controlled period
• Severity of adverse events during the 52-week placebo-controlled period
• Incidence of anti-therapeutic antibodies during the study relative to the incidence at baseline
• Frequency and severity of adverse events during the 52-week active-treatment extension and during the 24-week safety follow-up period.

E.5.2.1

Timepoint(s) of evaluation of this end point

52 weeks

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

Argentina

Australia

Brazil

Bulgaria

Canada

Chile

China

Colombia

Czech Republic

France

Germany

Hungary

India

Israel

Italy

Japan

Korea, Republic of

Mexico

Peru

Poland

Russian Federation

Slovakia

South Africa

Spain

Turkey

Ukraine

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 end of the study is defined as the date when the last patient, last visit (LPLV) occurs. The LPLV is expected to occur a maximum of 124 weeks after the last patient is enrolled and
randomized into the study. This timeframe includes the 52-week placebo-controlled period and a maximum of an additional 52-week active-treatment extension followed by the safety follow-up
period. All patients will be followed for safety for 24 weeks after the last dose of study treatment.

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:

1300

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

100

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

271

F.4.2.2

In the whole clinical trial

1400

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 study drug lebrikizumab is for experimental use only and it will not yet be approved for use at the time of the completion of this study. There are other therapies available to treat asthma. There are no plans for continued treatment with lebrikizumab or medical supervision of the patients after the end of the trial. Decisions concerning the care of the patient will be left with the patients’ treating physician after completion of the trial.

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

2012-06-06

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-06-06

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2012-10-01

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