Trial Outcomes & Findings for A Study Evaluating the Efficacy and Safety of Lebrikizumab in Adult Patients With Mild to Moderate Asthma (NCT NCT02104674)

Out of 313 enrolled participants, 3 were randomized but not treated during a 12-week treatment period where participants received blinded lebrikizumab/placebo or an open-label active comparator (montelukast sodium). The montelukast arm (active comparator) was included in the study design so that the sensitivity of the study could be evaluated with respect to the primary outcome measure of FEV1, and the secondary outcome measure of PEF.

A Study Evaluating the Efficacy and Safety of Lebrikizumab in Adult Patients With Mild to Moderate Asthma

FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. The active comparator treatment arm of open-label montelukast was included in the study design so that the sensitivity of the study could be evaluated with respect to the primary outcome measure, FEV1. Two mixed-effect models of repeated measures (MMRM) were used to estimate the absolute change from baseline values: one for the lebrikizumab vs. placebo primary comparison and the second for the montelukast vs. placebo sensitivity comparison.

Participants could only receive SABA therapy for asthma treatment as asthma reliever medication (\<10 puffs daily). SABA use was recorded in the eDiary. A mixed-effect model of repeated measures (MMRM) was used to estimate the absolute change from baseline values for the comparison between the double-blind lebrikizumab and placebo study arms.

The AQLQ\[S\] was used to assess the participant's asthma-specific health-related quality of life. The 32-item questionnaire contains four domains: activity limitations, symptoms, emotional function, and environmental stimuli. The AQLQ\[S\] has a recall specification of 2 weeks. Participants were asked to think about how they had been during the previous 2 weeks and to respond to each of the 32 questions on a 7-point scale (7 = not impaired at all; 1 = severely impaired). An increase in the AQLQ score indicates a better quality of life. The overall AQLQ score is the mean of all 32 responses and the individual domain scores are the means of the items in those domains. A mixed-effect model of repeated measures (MMRM) was used to estimate the change from baseline values.

PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. The active comparator treatment arm of open-label montelukast was included in the study design so that the sensitivity of the study could be evaluated with respect to this secondary outcome measure of PEF. A mixed-effect model of repeated measures (MMRM) was used to estimate the absolute change from baseline values for the sensitivity comparison between montelukast (open-label, active comparator) and placebo study arms.

Peak expiratory flow (PEF) is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. A mixed-effect model of repeated measures (MMRM) was used to estimate the absolute change from baseline values for the comparison between the double-blind lebrikizumab and placebo study arms.

Treatment failure was defined as a worsening of asthma symptoms (per investigator's assessment of participant report) in association with either relative decline in pre-bronchodilator FEV1 \>=20%; or \>=20% decline in morning pre-bronchodilator PEF on 2 consecutive days compared with baseline; or use of \>=10 puffs of albuterol metered dose inhaler (MDI); or \>=2 additional administrations (or any new use) of nebulized short-acting β-agonist (SABA) therapy within any calendar day; or need for any inhaled, oral, or parenteral corticosteroid or for a controller medication. The hazard ratio from the Cox Proportional Hazards model compared the risk of treatment failure for the lebrikizumab-treated and placebo participants.

Treatment failure was defined as a worsening of asthma symptoms (per investigator's assessment of participant report) in association with either relative decline in pre-bronchodilator FEV1 \>=20%; or \>=20% decline in morning pre-bronchodilator PEF on 2 consecutive days compared with baseline; or use of \>=10 puffs of albuterol metered dose inhaler (MDI); or \>=2 additional administrations (or any new use) of nebulized short-acting β-agonist (SABA) therapy within any calendar day; or need for any inhaled, oral, or parenteral corticosteroid or for a controller medication. Time to treatment failure was estimated using Kaplan-Meier method.

According to the protocol and statistical analysis plan, a single PK sample was collected per participant after the first dose at the expected time of the maximum serum lebrikizumab concentration.

According to the protocol and statistical analysis plan, the Tmax, Week1 (first dose) value was estimated on the basis of a single pharmacokinetic (PK) timepoint per participant after the first dose, which was taken at the expected time of the maximum serum lebrikizumab concentration.

According to the protocol and statistical analysis plan, the t1/2 was estimated based on the seven total PK samples collected per participant.