A Study of Lebrikizumab (RO5490255) in Participants With Severe Oral Corticosteroids (OCS) Dependent Asthma

Roche

Status and phase: Completed; Phase 2

Conditions: Asthma

Treatments: Drug: Lebrikizumab; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01987492

WB28182

2012-000190-24 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 230 patients

Sex: All

Ages: 12 to 75 years old

Volunteers: No Healthy Volunteers

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

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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230 participants in 3 patient groups, including a placebo group

Lebrikizumab High Dose

Experimental group

Description:

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.

Treatment:

Drug: Lebrikizumab

Lebrikizumab Low Dose

Experimental group

Description:

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.

Treatment:

Drug: Lebrikizumab

Placebo

Placebo Comparator group

Description:

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:

Drug: Placebo

Drug: Lebrikizumab