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

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2016-09-20
• Study First Submitted: 2016-09-27
• Study First Submitted QC: 2016-09-27
• Study First Posted: 2016-09-28
• Primary Completion: 2019-04-05
• Study Completion: 2019-07-26
• Disposition First Submitted: 2020-04-02
• Disposition First Submitted QC: 2020-04-02
• Disposition First Posted: 2020-04-08
• Results First Submitted: 2022-03-31
• Status Verified: 2022-11
• Results First Submitted QC: 2022-11-21
• Last Update Submitted: 2022-11-21
• Results First Posted: 2022-12-28
• Last Update Posted: 2022-12-28

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

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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

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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