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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01868061




Registration number
NCT01868061
Ethics application status
Date submitted
30/05/2013
Date registered
4/06/2013
Date last updated
19/05/2017

Titles & IDs
Public title
A Study of Lebrikizumab in Participants With Uncontrolled Asthma on Inhaled Corticosteroids and a Second Controller Medication
Scientific title
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 a Second Controller Medication
Secondary ID [1] 0 0
2013-000176-15
Secondary ID [2] 0 0
GB28689
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 (125 mg) - Participants will receive SC injection of lebrikizumab (125 mg) every 4 weeks for 104 weeks.

Experimental: Lebrikizumab (37.5 mg) - Participants will receive SC injection of lebrikizumab (37.5 mg) every 4 weeks for 104 weeks.

Placebo comparator: Placebo - Participants will receive SC injection of lebrikizumab matching placebo every 4 weeks for 52 weeks during placebo-controlled period and then SC injection of lebrikizumab at 125 or 37.5 mg for 52 weeks during active treatment extension period.


Treatment: Drugs: Lebrikizumab
Lebrikizumab will be administered as SC injection at 125 or 37.5 mg every 4 weeks, for 104 weeks.

Treatment: Drugs: Placebo
Lebrikizumab matching placebo will be administered as SC injection every 4 weeks for 52 weeks.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Rate of Asthma Exacerbations During the 52-Week Placebo-Controlled Period
Timepoint [1] 0 0
Baseline up to Week 52
Secondary outcome [1] 0 0
Absolute Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1)
Timepoint [1] 0 0
Baseline, Week 52
Secondary outcome [2] 0 0
Time to First Asthma Exacerbation
Timepoint [2] 0 0
Baseline up to Week 52
Secondary outcome [3] 0 0
Change From Baseline in Standardized Asthma Quality of Life Questionnaire (AQLQ) Score
Timepoint [3] 0 0
Baseline, Week 52
Secondary outcome [4] 0 0
Change from Baseline In Asthma Rescue Medication (Number of Puffs or Nebulized Treatments)
Timepoint [4] 0 0
Baseline, Week 52
Secondary outcome [5] 0 0
Rate of Urgent Asthma-Related Urgent Health Care Utilization
Timepoint [5] 0 0
Baseline up to Week 52
Secondary outcome [6] 0 0
Percentage of Participants With Adverse Events
Timepoint [6] 0 0
Baseline up to Week 124
Secondary outcome [7] 0 0
Percentage of Participants With Anti-Therapeutic Antibodies to Lebrikizumab
Timepoint [7] 0 0
Baseline up to Week 124 (assessed at Baseline, Weeks 4, 12, 24, 36, 52, 64, 76, 92, 104, 112, and 124)
Secondary outcome [8] 0 0
Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score
Timepoint [8] 0 0
Baseline, Week 52
Secondary outcome [9] 0 0
Minimum Serum Concentration (Cmin) of Lebrikizumab
Timepoint [9] 0 0
Predose (0 hour) on Weeks 4, 12, 24, 36, and 52

Eligibility
Key inclusion criteria
* Asthma diagnosis for greater than equal to (>/=) 12 months at Visit 1
* Bronchodilator response at Visit 1, 2, or 3
* Pre-bronchodilator FEV1 of 40 percent (%) - 80% predicted at both Visits 2 and 3
* On ICS therapy at a total daily dose of 500-2000 microgram (mcg) of fluticasone propionate dry powder inhaler (DPI) or equivalent for >/= 6 months prior to Visit 1
* On an eligible second controller medication (long-acting Beta-agonist [LABA], leukotriene receptor antagonist [LTRA], long-acting muscarinic antagonist [LAMA], or theophylline) for 6 months prior to Visit 1
* Uncontrolled asthma at Visit 1 and/or Visit 2, and at Visit 3
* Chest X-ray or computed tomography (CT) scan within 3 months prior to Visit 1 or chest X-ray during the screening period (prior to Visit 3) confirming the absence of other clinically significant lung disease
* Demonstrated adherence with controller medication during the screening period
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* History of severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of the lebrikizumab injection
* Maintenance oral corticosteroid therapy within 3 months of Visit 1
* Treatment with systemic (oral, intravenous [IV], or intramuscular [IM]) corticosteroids within 4 weeks prior to Visit 1 or during the screening period
* Treatment with intra-articular corticosteroids within 4 weeks prior to Visit 1 or during the screening period or anticipated need for intra-articular corticosteroids during the course of the study
* Infection requiring hospital admission for >/=24 hours or requiring treatment with IV or 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
* Active tuberculosis requiring treatment within 12 months prior to Visit 1
* Known immunodeficiency, including, but not limited to, human immunodeficiency virus (HIV) infection
* Evidence of acute or chronic hepatitis or known liver cirrhosis
* History of interstitial lung disease, chronic obstructive pulmonary disease (COPD), or other clinically significant lung disease other than asthma
* Known current malignancy or current evaluation for potential malignancy
* Current smoker or former smoker with a history of greater than (>) 10 pack-years
* History of alcohol or drug abuse
* Past and/or current use of any anti-interleukin (IL)-13 or anti-IL-4/IL-13 therapy, including lebrikizumab; use of other monoclonal antibody therapy, including omalizumab, within 6 months or 5 drug half-lives prior to Visit 1 (whichever is longer) or during screening
* Initiation of or change in allergen immunotherapy within 3 months prior to Visit 1 or during screening

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 3
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
31/07/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
2/01/2017
Sample size
Target
Accrual to date
Final
1068
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA
Recruitment hospital [1] 0 0
Concord Repatriation General Hospital; Department Thoracic Medicine - Sydney
Recruitment hospital [2] 0 0
AusTrials - Brisbane
Recruitment hospital [3] 0 0
Princess Alexandra Hospital, Department of Respiratory and Sleep Medicine - Brisbane
Recruitment hospital [4] 0 0
Respiratory Clinical Trials Pty Ltd - Toorak Gardens
Recruitment hospital [5] 0 0
The Lung Institute of Western Australia; Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
2139 - Sydney
Recruitment postcode(s) [2] 0 0
4075 - Brisbane
Recruitment postcode(s) [3] 0 0
4102 - Brisbane
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5065 - Toorak Gardens
Recruitment postcode(s) [5] 0 0
6009 - Nedlands
Recruitment outside Australia
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Barcelona
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Girona
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Ukraine
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Kiev Governorate
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Ukraine
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Cherkasy
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Zaporizhzhye
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Inverness
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Sheffield
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Westbury-on-Trym, Bristol

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 and safety of lebrikizumab in participants with asthma whose disease remains uncontrolled despite daily treatment with inhaled corticosteroid (ICS) therapy and at least one second controller medication. Participants will be randomized in 1:1:1 ratio to receive double-blind treatment with either lebrikizumab ("high" or "low") or placebo, administered as subcutaneous (SC) injection every 4 weeks for 52 weeks, in addition to their standard-of-care therapy. This will be followed by a 52-week double-blind active treatment extension. Participants who were assigned to placebo during the placebo-controlled period of the trial will be re-randomized at Week 52 to receive blinded SC lebrikizumab 37.5 milligrams (mg) or 125 mg every 4 weeks from Weeks 53 to 104. The anticipated time on study treatment is 104 weeks. After study treatment, all participants will complete a 20-week safety follow-up.
Trial website
https://clinicaltrials.gov/study/NCT01868061
Trial related presentations / publications
Chen M, Shepard K 2nd, Yang M, Raut P, Pazwash H, Holweg CTJ, Choo E. Overlap of allergic, eosinophilic and type 2 inflammatory subtypes in moderate-to-severe asthma. Clin Exp Allergy. 2021 Apr;51(4):546-555. doi: 10.1111/cea.13790. Epub 2021 Jan 7.
N Bauer R, Yang X, L Staton T, Olsson J, Holweg CTJ, R Arron J, Matthews JG, Choy DF. Seasonal variability of lung function and Asthma Quality of Life Questionnaire Scores in adults with uncontrolled asthma. BMJ Open Respir Res. 2019 Nov 11;6(1):e000406. doi: 10.1136/bmjresp-2019-000406. eCollection 2019.
Hanania NA, Korenblat P, Chapman KR, Bateman ED, Kopecky P, Paggiaro P, Yokoyama A, Olsson J, Gray S, Holweg CT, Eisner M, Asare C, Fischer SK, Peng K, Putnam WS, Matthews JG. Efficacy and safety of lebrikizumab in patients with uncontrolled asthma (LAVOLTA I and LAVOLTA II): replicate, phase 3, randomised, double-blind, placebo-controlled trials. Lancet Respir Med. 2016 Oct;4(10):781-796. doi: 10.1016/S2213-2600(16)30265-X. Epub 2016 Sep 5.
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

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01868061