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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01987492




Registration number
NCT01987492
Ethics application status
Date submitted
12/11/2013
Date registered
19/11/2013
Date last updated
22/05/2017

Titles & IDs
Public title
A Study of Lebrikizumab (RO5490255) in Participants With Severe Oral Corticosteroids (OCS) Dependent Asthma
Scientific title
A Phase II, Randomized, Double-Blind, Placebo Controlled, Multicenter Trial to Assess the Oral Corticosteroid-Sparing Effect of Lebrikizumab in Patients With Severe Corticosteroid Dependent Asthma
Secondary ID [1] 0 0
2012-000190-24
Secondary ID [2] 0 0
WB28182
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Asthma 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Asthma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Lebrikizumab
Treatment: Drugs - Placebo

Experimental: Lebrikizumab High Dose - Participants will receive lebrikizumab at high dose level as subcutaneous (SC) injection every 4 weeks during the 44-week DBPC period, followed by a 32-week ATE period, and during the LTE period.

Experimental: Lebrikizumab Low Dose - Participants will receive lebrikizumab at low dose level as SC injection every 4 weeks during the 44-week DBPC period, followed by a 32-week ATE period, and during the LTE period.

Placebo Comparator: Placebo - Participants will receive placebo matching to lebrikizumab SC injection every 4 weeks during the 44-week DBPC period. Participants will then be randomized to receive either high- or low-dose lebrikizumab every 4 weeks during the 32-week ATE period and will continue same treatment in the LTE period.


Treatment: Drugs: Lebrikizumab
Lebrikizumab will be administered as SC injections every 4 weeks at dose and schedule described in arm description.

Treatment: Drugs: Placebo
Placebo matching to lebrikizumab will be administered as SC injections every 4 weeks as per schedule described in arm description.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Relative Change From Baseline in Daily OCS Dose at Week 44
Timepoint [1] 0 0
Baseline, Week 44
Secondary outcome [1] 0 0
Absolute Change From Baseline in Daily OCS Dose at Week 44
Timepoint [1] 0 0
Baseline, Week 44
Secondary outcome [2] 0 0
Relative Change From Week 12 in Average OCS Dose at Week 44
Timepoint [2] 0 0
Week 12, Week 44
Secondary outcome [3] 0 0
Percentage of Participants Achieving at Least a 50 percent (%) Reduction in Their Daily OCS Dose at Week 44 Relative to Baseline
Timepoint [3] 0 0
Baseline, Week 44
Secondary outcome [4] 0 0
Percentage of Participants Discontinuing OCS Therapy or Having Achieved an Adrenal Maintenance Dose at Week 44 - Percentage of participants discontinuing OCS therapy or having achieved adrenal maintenance dose (cortisol level less than or equal to 100 nanomoles per liter) will be reported.
Timepoint [4] 0 0
Week 44
Secondary outcome [5] 0 0
Percentage of Participants With Asthma Exacerbations - An asthma exacerbation is defined as new or increased asthma symptoms (including wheeze, cough, dyspnea, chest tightness, or nocturnal awakenings due to these symptoms) that lead to treatment with systemic corticosteroids greater than or equal to (>/=) 30 milligrams (mg) or 0.5 mg per kilogram (kg) for >/=3 consecutive days or to hospitalization.
Timepoint [5] 0 0
Baseline up to Week 44
Secondary outcome [6] 0 0
Percentage of Participants With Adverse Events
Timepoint [6] 0 0
Baseline up to 24 weeks after last dose administration (up to a minimum of approximately 2 years)
Secondary outcome [7] 0 0
Percentage of Participants With Anti-therapeutic Antibodies (ATAs) Against Lebrikizumab
Timepoint [7] 0 0
Predose (0 hours) at Weeks 0, 4, 12, 24, 36, 44, 52, 64, and 76, at early discontinuation (up to a minimum of approximately 2 years), and at 24 weeks after last dose administration (up to a minimum of approximately 2 years)
Secondary outcome [8] 0 0
Minimum Observed Serum Lebrikizumab Concentration (Cmin)
Timepoint [8] 0 0
Predose (0 hours) at Weeks 4, 12, 24, 36, and 44

Eligibility
Key inclusion criteria
- Severe asthma despite intensive follow-up by an asthma specialist for >/=6 months
prior to Visit 1

- Baseline forced expiratory volume in 1 second (FEV1) >/=40% of predicted prior to
randomization

- Receiving high doses of inhaled glucocorticosteroids at a total daily dose of >/=1500
micrograms (mcg) beclomethasone dipropionate or equivalent and long-acting
beta-adrenoceptor agonist (LABA), with or without an additional controller, for at
least 3 months prior to Visit 1

- Chronic treatment with maintenance OCS for >/=6 months prior to Visit 1

- Assessment to ensure diagnosis of refractory asthma and OCS dependence on minimal
effective or maximum tolerated dose prior to Visit 1 with compliance
Minimum age
12 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- History of a severe allergic reaction or anaphylactic reaction to a biologic agent or
known hypersensitivity to any component of the lebrikizumab injection

- Asthma exacerbation within 28 days prior to Visit 1 or during screening (prior to
Visit 3)

- For adults: Active tuberculosis requiring treatment within the 12 months prior to
Visit 1

- For adolescents: History of active tuberculosis requiring treatment

- Evidence of acute or chronic hepatitis or known liver cirrhosis

- Known current malignancy or current evaluation for a potential malignancy

- History of interstitial lung disease, chronic obstructive pulmonary disease, or other
clinically significant lung disease other than asthma

- Infection requiring hospital admission or requiring treatment with intravenous (IV) or
intramuscular (IM) antibiotics within 4 weeks prior to Visit 1 or during screening

- Upper or lower respiratory tract infection within 4 weeks prior to Visit 1 or during
screening

- Active parasitic infection or Listeria monocytogenes infection within 6 months prior
to Visit 1 or during screening

- Current smoker or former smoker with a smoking history of more than 15 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 Visit 1

- Use of a licensed or investigational monoclonal antibody other than anti-interleukin
(IL)-13 or anti-IL-4/IL-13, including but not limited to, omalizumab, anti-IL-5, or
anti-IL-17, within 6 months or 5 drug half-lives (whichever is longer) prior to Visit
1

- Receipt of a live attenuated vaccine within the 4 weeks prior to Visit 1 during
screening or anticipation of receipt of a live attenuated vaccine throughout the study

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC,WA
Recruitment hospital [1] 0 0
Princess Alexandra Hospital, Department of Respiratory and Sleep Medicine - Brisbane
Recruitment hospital [2] 0 0
Monash Medical Centre; Respiratory and Sleep Medicine - Clayton
Recruitment hospital [3] 0 0
Institute for Respiratory Health Inc - Nedlands
Recruitment postcode(s) [1] 0 0
4102 - Brisbane
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
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United States of America
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Florida
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United States of America
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Georgia
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United States of America
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New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Oklahoma
Country [6] 0 0
United States of America
State/province [6] 0 0
Texas
Country [7] 0 0
United States of America
State/province [7] 0 0
Washington
Country [8] 0 0
Belgium
State/province [8] 0 0
Bruxelles
Country [9] 0 0
Belgium
State/province [9] 0 0
Genk
Country [10] 0 0
Belgium
State/province [10] 0 0
Gent
Country [11] 0 0
Canada
State/province [11] 0 0
Ontario
Country [12] 0 0
Czechia
State/province [12] 0 0
Brno
Country [13] 0 0
Czechia
State/province [13] 0 0
Liberec 1
Country [14] 0 0
Czechia
State/province [14] 0 0
Nový Jicín
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Czechia
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Rokycany
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Denmark
State/province [16] 0 0
Hellerup
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France
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Grenoble Cedex 9
Country [18] 0 0
France
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Le Kremlin Bicetre
Country [19] 0 0
France
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Lyon
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France
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Montpellier
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France
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Nantes
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France
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Nice Cedex 1
Country [23] 0 0
France
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Paris
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France
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Pessac
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France
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Strabourg
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Mexico
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Guadalajara
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Mexico
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Querétaro
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Netherlands
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Amsterdam
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Netherlands
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Hoofddorp
Country [30] 0 0
Netherlands
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Nieuwegein
Country [31] 0 0
New Zealand
State/province [31] 0 0
Auckland
Country [32] 0 0
New Zealand
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Dunedin
Country [33] 0 0
New Zealand
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Tauranga
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New Zealand
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Wellington
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Poland
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Krakow
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Poland
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Lodz
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Poland
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Ostrow Wielkopolski
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Poland
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Ruda Slaska
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Poland
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Warszawa
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Poland
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Wroclaw
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Puerto Rico
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Caguas
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Puerto Rico
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Cidra
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Slovakia
State/province [43] 0 0
Levice
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Slovakia
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Spisska Nova Ves
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Slovenia
State/province [45] 0 0
Golnik
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Spain
State/province [46] 0 0
La Coruña
Country [47] 0 0
Spain
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Barcelona
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Spain
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Salamanca
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Spain
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Valencia
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United Kingdom
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Belfast
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United Kingdom
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Birmingham
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United Kingdom
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Glasgow
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United Kingdom
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Hampshire
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United Kingdom
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Leicester
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United Kingdom
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London
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United Kingdom
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Manchester
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United Kingdom
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Newcastle upon Tyne
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United Kingdom
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Plymouth
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United Kingdom
State/province [59] 0 0
Sheffield

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This randomized, multicenter, double-blind, placebo-controlled, parallel-group study will
evaluate the efficacy of lebrikizumab compared with placebo, as measured by the ability of
participants to achieve lower daily doses of OCS, among those with severe
corticosteroid-dependent asthma. Prednisone/prednisolone will be the OCS therapy prescribed.
Participants will be randomized to receive lebrikizumab or matching placebo for 44 weeks in a
double-blind, placebo-controlled (DBPC) period. Those who complete the 44-week period may
continue into a 32-week active treatment extension (ATE) period, during which all
participants will receive lebrikizumab treatment. Following completion of the ATE period,
participants who have both tolerated and derived benefit from treatment with lebrikizumab may
continue their lebrikizumab treatment into a long-term extension (LTE) period. Participants
will transition to 24 weeks of safety follow-up upon discontinuation of study drug.
Trial website
https://clinicaltrials.gov/show/NCT01987492
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications