A Study to Assess the Efficacy and Safety of MSTT1041A in Participants With Uncontrolled Severe Asthma
- 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
- 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
- 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)
Genesis Clinical Research & Consulting, LLC
🇺🇸Fall River, Massachusetts, United States
Cheema Research
🇨🇦Mississauga, Ontario, Canada
Emerald Coast Research Associates
🇺🇸Panama City, Florida, United States
Asthma, Allergy & Sinus Center
🇺🇸Baltimore, Maryland, United States
Midwest Clinical Research LLC
🇺🇸Saint Louis, Missouri, United States
Clinical Research Solutions PC
🇺🇸Knoxville, Tennessee, United States
TTS Research
🇺🇸Boerne, Texas, United States
Metroplex Pulmonology & Sleep Center
🇺🇸McKinney, Texas, United States
Fifth MHAT - Sofia EAD
🇧🇬Sofia, Bulgaria
Aggarwal and Associates
🇨🇦Brampton, Ontario, Canada
EUC Klinika Ostrava a.s.
🇨🇿Ostrava-Poruba, Czechia
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Centrum Medyczne ALL-MED
🇵🇱Krakow, Poland
Clinical Emergency Hospital n.a.N.V. Soloviev
🇷🇺Yaroslavl, Moskovskaja Oblast, Russian Federation
Municipal Healthcare Institution City Clinical Hospital #3 named after M.A. Podgorbunskogo
🇷🇺Kemerovo, Russian Federation
St. Petersburg State Medical University n.a. I.P. Pavlov
🇷🇺St. Petersburg, Russian Federation
SI National Institute of Phthisiology and Pulmonology n.a. F.G.Yanovskyi under NAMS of Ukraine
🇺🇦Kyiv, Ukraine
Kyiv City Clinical Hospital #8
🇺🇦Kyiv, Ukraine
Pioneer Research Solutions
🇺🇸Houston, Texas, United States
Western States Clinical Research, Inc
🇺🇸Wheat Ridge, Colorado, United States
IMMUNOe Research Centers
🇺🇸Centennial, Colorado, United States
Asthma & Allergy; Associates, P.C.
🇺🇸Colorado Springs, Colorado, United States
Integrity People Services Research Company
🇺🇸Oklahoma City, Oklahoma, United States
Alabama Allergy & Asthma
🇺🇸Birmingham, Alabama, 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
Allergy & Asthma Consultants
🇺🇸Redwood City, California, United States
Bensch Research Associates
🇺🇸Stockton, California, United States
Allergy and Asthma Clinical Research, Inc.
🇺🇸Walnut Creek, California, United States
Yale University School Of Medicine
🇺🇸New Haven, Connecticut, United States
Atlanta Allergy & Asth Clin PC
🇺🇸Stockbridge, Georgia, United States
Florida Premier Research Institute
🇺🇸Winter Park, Florida, United States
Asthma & Allergy of Idaho
🇺🇸Twin Falls, Idaho, United States
Chesapeake Clinical Research Inc - CRN
🇺🇸Baltimore, Maryland, United States
The Allergy and Asthma Center
🇺🇸Bellevue, Nebraska, United States
American Health Research Inc.
🇺🇸Charlotte, North Carolina, United States
Allergy & Respiratory Center
🇺🇸Canton, Ohio, United States
Vital Prospects Clin Res Pc
🇺🇸Tulsa, Oklahoma, United States
Temple University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Asthma & Allergy Physicians of Rhode Island Clinical Research Institute (AAPRI CRI)
🇺🇸Warwick, Rhode Island, United States
Elliot J. Ginchansky, MD, PA
🇺🇸Dallas, Texas, United States
Commonwealth Clinical Research Specialists
🇺🇸Richmond, Virginia, United States
Allergy Associates of Utah
🇺🇸Murray, Utah, United States
Washington Univ School of Med
🇺🇸Seattle, Washington, United States
Allergy & Asthma Research Center
🇺🇸San Antonio, Texas, United States
Fundacion Cidea
🇦🇷Buenos Aires, Argentina
INSARES
🇦🇷Mendoza, Mendoza City, Argentina
Fundacion Scherbovsky
🇦🇷Mendoza, Argentina
CEMER Centro Medico de Enfermedades Respiratorias
🇦🇷Vicente López, Argentina
Cliniques Universitaires St-Luc
🇧🇪Bruxelles, Belgium
Military Medical Academy HBAT
🇧🇬Pleven, Bulgaria
SHATPPD Dr. Dimitar Gramatikov, Ruse Ltd.
🇧🇬Ruse, Bulgaria
Medical Centre Mladost Med 1 EOOD
🇧🇬Sofia, Bulgaria
First MHAT; Clinic of Neurology
🇧🇬Sofia, Bulgaria
Specialised Hospital for Active Treatment of Pulmonary Deseases "Sv. Sofia", Third Clinic for Non-Sp
🇧🇬Sofia, Bulgaria
Inspiration Research
🇨🇦Toronto, Ontario, Canada
Anil Dhar Professional Medicine Corporation
🇨🇦Windsor, Ontario, Canada
Alergologie Teplice, s.r.o.
🇨🇿Teplice, Czechia
Ordinace pro tuberkulozu a respiracni nemoci
🇨🇿Strakonice, Czechia
KASMED s.r.o.
🇨🇿Tabor, Czechia
Pneumologisches Forschungsinstitut Hohegeest
🇩🇪Geesthacht, Germany
POIS Leipzig Gbr
🇩🇪Leipzig, Germany
Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Medizinische Klinik, Pneumologie
🇩🇪Mainz, Germany
Universitatsklinikum Munster
🇩🇪Münster, Germany
Greenlane Clinical Centre
🇳🇿Auckland, New Zealand
Medical Research Institute of New Zealand
🇳🇿Wellington, New Zealand
Clinica Internacional
🇵🇪Lima, Peru
Abk Reuma Srl- Medicentro
🇵🇪Lima, Peru
Hospital Santa Rosa Piura
🇵🇪Piura, Peru
Centrum Medycyny Oddechowej Robert M. Mróz
🇵🇱Bialystok, Poland
Clinica San Borja
🇵🇪Lima, Peru
Niepubliczny Zaklad Opieki Zdrowotnej Centrum Medyczne ProMiMed sp z o.o. sp.k.
🇵🇱Kraków, Poland
Malopolskie Centrum Alergologii
🇵🇱Krakow, Poland
Przedsiebiorstwo Podmiotu Leczniczego Poradnie Specjalistyczne MAGMED
🇵🇱Radom, Poland
Specjalistyczna Poradnia Pulmonologiczna
🇵🇱Ostrow Wielkopolski, Poland
ALERGO-MED Specjalistyczna Przychodnia Lekarska Sp. z o. o
🇵🇱Tarnow, Poland
NZOZ Lekarze Specjaliści J. Małolepszy i Partnerzy
🇵🇱Wroclaw, Poland
Theramed SRL
🇷🇴Brasov, Romania
Spitalul Clinic de Pneumoftiziologie Leon Daniello Cluj-Napoca, Sectia Clinica Pneumologie I
🇷🇴Cluj-Napoca, Romania
Spitalul Clinic de Boli Infectioase si Pneumoftiziologie Victor Babes Craiova
🇷🇴Craiova, Romania
Fundatia CardioPrevent
🇷🇴Timisoara, Romania
Dr. Victor Babes Pneumology and Infectious Diseases Clinical Hospital
🇷🇴Timisoara, Romania
I.M. Sechenov Moscow State Medical University the Ministry of Health and Social Development of RF
🇷🇺Moscow, Russian Federation
City Clinical Hospital #2
🇷🇺Novosibirsk, Russian Federation
Novosibirsk Municipal Clinical Hospital For Emergency Medicine #2
🇷🇺Novosibirsk, Russian Federation
Ryazan State Medical University Named after I.P.Pavlov
🇷🇺Ryazan, Russian Federation
SHI Ctr Occupational Pathology
🇷🇺St. Petersburg, Russian Federation
Clinic Reavita LLC
🇷🇺St. Petersburg, Russian Federation
Siberian State Medical University
🇷🇺Tomsk, Russian Federation
Tiervalei Trial Centre
🇿🇦Cape Town, South Africa
St Augustines Hospital; Infectoilogy
🇿🇦Durban, South Africa
Aliwal Shoal Medical Center
🇿🇦Umkomaas, South Africa
University of Cape Town Lung Institute; Lung Clinical Research
🇿🇦Cape Town, South Africa
Vawda Z.Fa Practice
🇿🇦Durban, South Africa
Municipal institution; City hospital #1; Department of Therapy
🇺🇦Zaporizhzhia, Kherson Governorate, Ukraine
Kyiv City Tuberculosis Hospital #1; Department of Differential Diagnosis of Lung Diseases
🇺🇦Kyiv, KIEV Governorate, Ukraine
Regional Phthisiology and Pulmonology Center
🇺🇦Ivano-Frankivsk, Ukraine
SI Institute of Therapy n.a. L.T. Mala of National Academy of Medical Sciences of Ukraine
🇺🇦Kharkiv, Ukraine
Municipal Institution of Kyiv Regional Council Kyiv Regional Clinical Hospital
🇺🇦Kyiv, Ukraine
City Hospital #1
🇺🇦Mykolaiv, Ukraine
Municipal Institution Odesa Regional Clinical Hospital
🇺🇦Odesa, Ukraine
Small Business Private Enterprise Medical Centre Pulse
🇺🇦Vinnytsya, Ukraine
MediTrial s.r.o.
🇨🇿Jindřichův Hradec, Czechia
Advances in Medicine
🇺🇸Rancho Mirage, California, United States
Instituto Especialidades de la Salud Rosario
🇦🇷Rosario, Argentina
Private Practice Dr Jean Benoit Martinot
🇧🇪Erpent, Belgium
National Multiprofile Hospital Tsar Boris III
🇧🇬Sofia, Bulgaria
Alitera - Med - Medical Center EOOD
🇧🇬Sofia, Bulgaria
SPZOZ Uniwersytecki Szpital Kliniczny nr 1 im. Norberta Barlickiego Uniwersytetu Medycznego w Lodzi
🇵🇱Lodz, Poland
Ewa Pisarczyk-Bogacka Specjalistyczna Praktyka Lekarska
🇵🇱Wroclaw, Poland
LLC - ABC Medicina
🇷🇺Moscow, Sankt Petersburg, Russian Federation
City Hospital #40 of Resort Administrative District
🇷🇺St. Petersburg, Russian Federation
Public Institution City Clinical Hospital # 6 of Dnipropetrovsk Regional Board
🇺🇦Dnepropetrovsk, Ukraine
Ukrainian State Institute of Medical and Social Problems of Disability
🇺🇦Dnipropetrovsk, Ukraine
Meharry Medical College; Clinical Trials Office
🇺🇸Nashville, Tennessee, United States
Investigaciones en Patologias Respiratorias
🇦🇷San Miguel de Tucuman, Argentina
Medical Center Tara OOD
🇧🇬Veliko Tarnovo, Bulgaria
Del Sol Research Management
🇺🇸Tucson, Arizona, United States
C.I.C. Mauricie
🇨🇦Trois-Rivières, Quebec, Canada
Infinity Medical Research Inc
🇺🇸North Dartmouth, Massachusetts, United States
Centro Respiratorio Quilmes
🇦🇷Quilmes, Argentina
INAER
🇦🇷Ciudad Autónoma de Buenos Aires, Argentina
Centro Modelo de Cardiologia
🇦🇷San Miguel de Tucuman, Argentina
Uni. Multiprofile Hosp. for Active Treatment-Aleksandrovska
🇧🇬Sofia, Bulgaria
Medical Center "Nov Rehabilitatsionen Tsentar", EOOD
🇧🇬Stara Zagora, Bulgaria
Regional Municipal Institution Chernivtsi Regional Clinical Hospital
🇺🇦Chernivtsi, Chernihiv Governorate, Ukraine
Instituto de Diagnóstico ABC; Servicio de Investigación de Patologías Alérgicas
🇦🇷Rosario, Argentina
Medical Center N.I. Pirogov EOOD
🇧🇬Sofia, Bulgaria
Clinica Ricardo Palma; THORAX
🇵🇪Lima, Peru
Instituto Peruano de Investigacion en Ciencias Medicas
🇵🇪Lima, Peru
City Hospital #5
🇷🇺Barnaul, Russian Federation
Spartanburg Medical Research
🇺🇸Spartanburg, South Carolina, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States