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

Phase 2

Completed

Conditions: Asthma

Interventions: Drug: MSTT1041A
Drug: Placebo

Registration Number: NCT02918019

Lead Sponsor: Hoffmann-La Roche

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 517

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MSTT1041A 70 mg	MSTT1041A	Participants will receive MSTT1041A 70 mg, subcutaneously every 4 weeks from randomization through Week 50.
MSTT1041A 210 mg	MSTT1041A	Participants will receive MSTT1041A 210 milligrams (mg), subcutaneously every 4 weeks from randomization through Week 50.
MSTT1041A 490 mg	MSTT1041A	Participants will receive MSTT1041A 490 mg, subcutaneously every 4 weeks from randomization through Week 50.
Placebo	Placebo	Participants will receive placebo matched with MSTT1041A, subcutaneously every 4 weeks from randomization through Week 50.

Primary Outcome Measures

Name	Time	Method
Reduction in Rate of Asthma Exacerbations	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 Outcome Measures

Name	Time	Method
Absolute Change in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1)	Baseline to Week 54	FEV1 measures how much air a person can exhale during the first second of a forced breath. Adjusted means are reported.
Achievement in Improvement in Standardized Asthma Quality-of-Life Questionnaire (AQLQ(S)) Score	Week 54	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.
Percentage of Participants With Anti-Drug Antibodies (ADAs)	Baseline	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.
Proportion of Weeks Without Patient-Reported Asthma-Related Nighttime Awakenings	Baseline through Week 54	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 to First Asthma Exacerbation	52 Weeks	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.
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)	The incidence of ADAs at post-baseline timepoints was defined as the proportion of the study population found to have developed treatment-emergent ADAs.
Absolute Change in Patient-Reported Use of Short-Acting Rescue Therapy	Baseline to Week 54	Adjusted mean values are all equal to zero.
Percentage of Participants With Adverse Events	Baseline to Week 54	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.
Absolute Change in Patient-Reported Daytime Asthma Symptom Severity as Measured by the Asthma Daily Symptom Diary (ADSD)	Baseline to Week 54	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.

Trial Locations

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
Jonathan Corren MD, Inc.
🇺🇸
Los Angeles, California, United States
Office of Robert N Wolfe MD
🇺🇸
Los Angeles, California, United States
Advances in Medicine
🇺🇸
Rancho Mirage, California, United States
Allergy & Asthma Consultants
🇺🇸
Redwood City, California, United States
Bensch Research Associates
🇺🇸
Stockton, California, United States
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Alabama Allergy & Asthma
🇺🇸Birmingham, Alabama, United States