A Phase IIb, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Dose-Ranging Study to Assess the Efficacy and Safety of MSTT1041A in Patients With Uncontrolled Severe Asthma
Overview
- Phase
- Phase 2
- Intervention
- MSTT1041A
- Conditions
- Asthma
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 517
- Locations
- 138
- Primary Endpoint
- Reduction in Rate of Asthma Exacerbations
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
This is a Phase IIb, randomized, placebo-controlled, double-blind, multicenter, multi-arm study which will evaluate efficacy, safety, and pharmacokinetic of MSTT1041A compared with placebo as add-on therapy in participants with severe, uncontrolled asthma who are receiving medium- or high-dose inhaled corticosteroid (ICS) therapy and at least one of the following additional controller medications: long-acting beta-agonists (LABA), leukotriene modifier (LTM), long-acting muscarinic antagonist (LAMA), or long-acting theophylline preparation. The total duration of this study for each participant is approximately 70 weeks including screening, run-in, treatment, and follow-up.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Body mass index (BMI) of 18 to 38 kilogram/square meter (kg/m\^2) and weight \>= 40 kg at screening
- •Documented physician-diagnosed asthma
- •On high dose inhaled corticosteroid (ICS) therapy plus at least one additional allowed controller medication
- •Forced expiratory volume in 1 second (FEV1) of 40% to 80% of predicted
- •Evidence of uncontrolled asthma
- •Use of contraceptive measures
Exclusion Criteria
- •Diagnosis of mimics of asthma
- •Diagnosis of occupational asthma, aspirin-sensitive asthma, asthma chronic obstructive pulmonary disease overlap syndrome, or bronchiolitis, as determined by the investigator
- •Pregnant or lactating, or intending to become pregnant during the study or within 20 weeks after the last dose of MSTT1041A
- •Recent history of smoking
- •History or evidence of substance abuse that would pose a risk to participants safety, interfere with the conduct of the study, have an impact on the study results
- •Asthma exacerbation within 4 weeks prior to screening
- •Intubation for respiratory failure due to asthma within 12 months prior to screening
- •Comorbid conditions that may interfere with evaluation of investigational medicinal product
- •Known sensitivity to any of the active substances or their excipients to be administered during dosing
- •Positive pregnancy test
Arms & Interventions
MSTT1041A 210 mg
Participants will receive MSTT1041A 210 milligrams (mg), subcutaneously every 4 weeks from randomization through Week 50.
Intervention: MSTT1041A
MSTT1041A 490 mg
Participants will receive MSTT1041A 490 mg, subcutaneously every 4 weeks from randomization through Week 50.
Intervention: MSTT1041A
MSTT1041A 70 mg
Participants will receive MSTT1041A 70 mg, subcutaneously every 4 weeks from randomization through Week 50.
Intervention: MSTT1041A
Placebo
Participants will receive placebo matched with MSTT1041A, subcutaneously every 4 weeks from randomization through Week 50.
Intervention: Placebo
Outcomes
Primary Outcomes
Reduction in Rate of Asthma Exacerbations
Time Frame: Baseline to Week 54
Asthma exacerbation was defined as new or increased asthma symptoms (wheezing, coughing, dyspnea, chest tightness, and/or nighttime awakenings due to these symptoms) that result in one or both of the following: Hospitalization or emergency department visit with administration of systemic corticosteroid treatment; Treatment with systemic corticosteroids for at least 3 days, or a long-acting depot corticosteroid preparation with a therapeutic effectiveness of at least 3 days. Adjusted rates for the overall mITT population (all participants that received at least one dose of study drug) were estimated using Poisson regression and adjusted for blood eosinophil level at the first visit, the number of asthma exacerbations requiring systemic corticosteroids in the 12 months prior to study entry, the total daily ICS dose at the first visit, and geographic region, with patient time at risk used as an offset term.
Secondary Outcomes
- Absolute Change in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1)(Baseline to Week 54)
- Achievement in Improvement in Standardized Asthma Quality-of-Life Questionnaire (AQLQ(S)) Score(Week 54)
- Percentage of Participants With Anti-Drug Antibodies (ADAs)(Baseline)
- Proportion of Weeks Without Patient-Reported Asthma-Related Nighttime Awakenings(Baseline through Week 54)
- Time to First Asthma Exacerbation(52 Weeks)
- Serum Concentration of Astegolimab (MSTT1041A)(Weeks 26 and 54)
- Percentage of Participants With Treatment-Emergent ADAs(From baseline to the first appearance of ADAs at any point post-baseline (up to Week 54))
- Absolute Change in Patient-Reported Use of Short-Acting Rescue Therapy(Baseline to Week 54)
- Percentage of Participants With Adverse Events(Baseline to Week 54)
- Absolute Change in Patient-Reported Daytime Asthma Symptom Severity as Measured by the Asthma Daily Symptom Diary (ADSD)(Baseline to Week 54)