MENSA (Trial 2) Study Design and Primary Endpoint
MENSA (Trial 2) Study Design and Primary Endpoint1
Study Description: 32-week, multicenter, randomized, double-blind, double-dummy, placebo-controlled study comparing treatment with NUCALA or mepolizumab 75 mg intravenous (IV) to placebo, each added to standard of care (SOC) in 576 patients 12 years and older with severe asthma with an eosinophilic phenotype, identified by blood eosinophil counts of ≥150 cells/μL at baseline or ≥300 cells/μL within the last 12 months.
Primary Endpoint: Frequency of exacerbations.*
Results: Exacerbations/year 0.83 for NUCALA vs 1.74 for placebo (53% reduction; P<0.001).
*Exacerbations of asthma were defined as the worsening of asthma that required use of oral/systemic corticosteroids and/or hospitalization and/or emergency department (ED) visits; for patients on maintenance oral/systemic corticosteroids, exacerbations were defined as requiring at least double the existing maintenance dose for at least 3 days.
SOC=regular treatment with high-dose inhaled corticosteroids (ICS) (defined as ≥880 μg of fluticasone propionate [FP], or the equivalent, per day in patients ≥18 years of age, and ≥440 μg of FP, or the equivalent, per day in patients 12 to 17 years of age) and at least 1 other controller with or without oral corticosteroids (OCS).4
SIRIUS (Trial 3) Study Design and Primary Endpoint2
Study Description: 24-week, multicenter, randomized, double-blind, placebo-controlled study comparing treatment with NUCALA to placebo in 135 patients 12 years and older with severe asthma with an eosinophilic phenotype, identified by blood eosinophil counts of ≥150 cells/μL at baseline or ≥300 cells/μL in the past 12 months. Patients required 5 mg to 35 mg of prednisone or its equivalent per day in addition to regular use of high-dose ICS plus an additional controller. Patients were not required to have a history of exacerbations in the previous 12 months.
Primary Endpoint: Percent reduction in daily OCS dose (Weeks 20 to 24) while maintaining asthma control.
Results: NUCALA reduced daily OCS dose while maintaining asthma control vs placebo (P=0.008).
COLUMBA Study Design Open-Label Long-Term Safety Study3,4
Study Description: 4.5-year, multicenter, open-label long-term study assessing the safety, immunogenicity and efficacy of NUCALA in 347 patients 12 years and older with severe asthma with an eosinophilic phenotype previously treated in DREAM (Trial 1)† at least 12 months prior and met eligibility criteria. All patients received NUCALA added to asthma controller therapy.
Primary Endpoints: Long-term safety, including adverse events (AEs), serious adverse events (SAEs), and immunogenicity.
Results: Most frequent AEs (≥20%): viral upper respiratory tract infection, 49%; headache, 29%; asthma‡, 27%; upper respiratory tract infection, 23%; bronchitis, 21%. Two SAEs occurred in ≥1% of patients: asthma, 10%; and pneumonia, 2%. A total of 8% of patients had a positive anti-drug antibody result, but all were negative for neutralizing antibodies.
Secondary Endpoints: Frequency of exacerbations, asthma control (ACQ-5 score), and lung function (FEV1).
Exacerbations: The annualized exacerbation rate was 0.68 (95% CI: 0.60 to 0.78).
Asthma control: The mean change from baseline in ACQ-5 score was -0.47 points at both Week 12 and end of study.
Lung Function: The mean change from baseline in pre-bronchodilator FEV1 at Week 12 was 124 mL, and gradually declined to approximate baseline values at end of study.
Results are descriptive.
†DREAM (Trial 1): 52-week study comparing mepolizumab IV to placebo IV added to SOC in 616 patients with severe asthma. Primary Endpoint: Frequency of exacerbations. Results: Exacerbations/year 1.24 for mepolizumab 75 mg vs 2.40 for placebo (48% reduction, P<0.0001).5
‡Asthma reported as an AE means worsening or exacerbation of asthma.
ACQ=Asthma Control Questionnaire.
FEV1= forced expiratory volume in 1 second.