A Study to Assess the Efficacy and Safety of MSTT1041A in Participants With Uncontrolled Severe Asthma

Hoffmann-La Roche517 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

517

Conditions

Asthma

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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

Locations (138)

Alabama Allergy & Asthma

Birmingham, Alabama, United States

Del Sol Research Management

Tucson, Arizona, United States

Kern Allergy Med Clinic, Inc.

Bakersfield, California, United States

Allergy & Asthma Care Center of Southern California

Long Beach, California, United States

CA Allergy & Asthma Med Grp; Medical Group, Inc.

Los Angeles, California, United States

Outcomes

Primary Outcomes

Reduction in Rate of Asthma Exacerbations

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.

Time frame: Baseline to Week 54

Secondary Outcomes

Absolute Change in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1)

FEV1 measures how much air a person can exhale during the first second of a forced breath. Adjusted means are reported.

Time frame: Baseline to Week 54

Time to First Asthma Exacerbation

Time frame: 52 Weeks

Achievement in Improvement in Standardized Asthma Quality-of-Life Questionnaire (AQLQ(S)) Score

The AQLQ measures the functional problems (physical, emotional, social, and occupational) most troublesome to adults (17-70 years) with asthma. There are 32 questions in 4 domains - symptoms, activity limitation, emotional function, and environmental stimuli - scored on a 7 point scale, with 7= no impairment and 1= severely impaired. For this study, improvement achievement was defined as an increase of at least 0.5 points from baseline to week 54. Adjusted rates are reported.

Time frame: Week 54

Absolute Change in Patient-Reported Use of Short-Acting Rescue Therapy

Adjusted mean values are all equal to zero.

Time frame: Baseline to Week 54

Proportion of Weeks Without Patient-Reported Asthma-Related Nighttime Awakenings

The adjusted mean proportion of weeks without a nighttime awakening from baseline through week 54 are reported. The proportion of weeks is expressed as a percentage.

Time frame: Baseline through Week 54

Absolute Change in Patient-Reported Daytime Asthma Symptom Severity as Measured by the Asthma Daily Symptom Diary (ADSD)

The ADSD is a 6-item daily measure of asthma symptom severity that assesses three core categories of asthma symptoms: breathing symptoms, chest symptoms, and cough. Symptoms are rated at their worst using an 11-point numeric rating scale ranging from 0 (no symptoms) to 10 (the worst symptoms imaginable). Adjusted means are reported.

Time frame: Baseline to Week 54

Percentage of Participants With Adverse Events

An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

Time frame: Baseline to Week 54

Percentage of Participants With Anti-Drug Antibodies (ADAs)

The prevalence of ADAs at baseline was defined as the proportion of the evaluable participant population in a study that is ADA positive at baseline.

Time frame: Baseline

Serum Concentration of Astegolimab (MSTT1041A)

Time frame: Weeks 26 and 54

Percentage of Participants With Treatment-Emergent ADAs

The incidence of ADAs at post-baseline timepoints was defined as the proportion of the study population found to have developed treatment-emergent ADAs.

Time frame: From baseline to the first appearance of ADAs at any point post-baseline (up to Week 54)