Overview

Condition asthma
Treatments lebrikizumab, placebo
Phase phase 2
Sponsor Hoffmann-La Roche
Start date February 2014
End date December 2016
Trial size 225 participants
Trial identifier NCT01987492, 2012-000190-24, WB28182

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 into a long-term extension (LTE) which will last until 2018. Participants will transition to 24 weeks of safety follow-up upon discontinuation of study drug.

Recruiting in the following locations…

United States No locations recruiting
Other Countries France, Puerto Rico, and United Kingdom

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose treatment
Arm
(Experimental)
Participants will complete a 44-week DBPC period. The first lebrikizumab high-dose SC injection will occur on Day 1 and will be repeated every 4 weeks. In the ATE and LTE, participants will continue to receive the same regimen of lebrikizumab.
lebrikizumab
Lebrikizumab will be administered as high- or low-dose SC injections every 4 weeks for up to 44 weeks during the DBPC period, up to 32 weeks during the ATE, and until the end of treatment provision (31-Mar-2018) in the LTE.
(Experimental)
Participants will complete a 44-week DBPC period. The first lebrikizumab low-dose SC injection will occur on Day 1 and will be repeated every 4 weeks. In the ATE and LTE, participants will continue to receive the same regimen of lebrikizumab.
lebrikizumab
Lebrikizumab will be administered as high- or low-dose SC injections every 4 weeks for up to 44 weeks during the DBPC period, up to 32 weeks during the ATE, and until the end of treatment provision (31-Mar-2018) in the LTE.
(Placebo Comparator)
Participants will complete a 44-week DBPC period. The first SC injection will occur on Day 1 and will be repeated every 4 weeks. In the ATE, participants will be re-randomized to receive either high- or low-dose lebrikizumab every 4 weeks. In the LTE, participants will continue to receive the same dose as in the ATE.
placebo
Placebo will be administered as SC injections every 4 weeks for up to 44 weeks during the DBPC period. Thereafter, participants may be re-randomized to receive lebrikizumab in the ATE and LTE periods.

Primary Outcomes

Measure
Relative change in daily OCS dose
time frame: From Baseline to Week 44

Secondary Outcomes

Measure
Absolute change in daily OCS dose
time frame: From Baseline to Week 44
Rate of asthma exacerbations during the DBPC period
time frame: Up to 44 weeks
Percentage of participants achieving at least a 50% reduction in their daily OCS dose relative to Baseline
time frame: From Baseline to Week 44
Percentage of participants discontinuing OCS therapy or having achieved an adrenal maintenance dose
time frame: From Baseline to Week 44
Relative change in average OCS dose during the OCS reduction phase
time frame: From Week 12 to Week 44
Frequency and severity of treatment-emergent adverse events during the DBPC, ATE, LTE, and safety follow-up periods
time frame: Up to approximately 4.5 years

Eligibility Criteria

Male or female participants from 12 years up to 75 years old.

Inclusion Criteria: - Adults 12 to 75 years of age at the time of informed consent - Severe asthma despite intensive follow-up by an asthma specialist for at least 6 months prior to Visit 1 - Baseline forced expiratory volume in 1 second (FEV1) at least 40% of predicted prior to randomization - Receiving high doses of inhaled glucocorticosteroids at a total daily dose of at least 1500 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 at least 6 months prior to Visit 1 - Assessment to ensure diagnosis of refractory asthma and OCS dependence on minimal effective or maximum tolerated dose with compliance 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 >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

Additional Information

Official 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
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Hoffmann-La Roche.