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

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

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 Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: MSTT1041A; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 517
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1121ABE
    • Fundacion Cidea
  • Ciudad Autónoma de Buenos Aires, Argentina, C1425BEN
    • INAER
  • Mendoza, Argentina, M5500AYB
    • Fundación Scherbovsky
  • Mendoza, Mendoza City, Argentina, M5500CCG
    • INSARES
  • Quilmes, Argentina, B1878FNR
    • Centro Respiratorio Quilmes
  • Rosario, Argentina, S2000DBS
    • Instituto Especialidades de La Salud Rosario
  • Rosario, Argentina, S2000JKE
    • Instituto de Diagnóstico ABC; Servicio de Investigación de Patologías Alérgicas
  • San Miguel de Tucuman, Argentina, T4000IAR
    • Investigaciones en Patologias Respiratorias
  • San Miguel de Tucuman, Argentina, 4000
    • Centro Modelo de Cardiología
  • Vicente López, Argentina, B1602DQD
    • CEMER Centro Medico de Enfermedades Respiratorias
• Belgium
  • Bruxelles, Belgium, 1200
    • Cliniques Universitaires St-Luc
  • Erpent, Belgium, 5101
    • Private Practice Dr Jean Benoit Martinot
• Bulgaria
  • Pleven, Bulgaria, 5800
    • Military Medical Academy HBAT
  • Ruse, Bulgaria, 7002
    • SHATPPD Dr. Dimitar Gramatikov, Ruse Ltd.
  • Sofia, Bulgaria, 1233
    • Fifth MHAT - Sofia EAD
  • Sofia, Bulgaria, 1142
    • First MHAT; Clinic of Neurology
  • Sofia, Bulgaria, 1000
    • Medical Centre Mladost Med 1 EOOD
  • Sofia, Bulgaria, 1233
    • National Multiprofile Hospital Tsar Boris III
  • Sofia, Bulgaria, 1431
    • Specialised Hospital for Active Treatment of Pulmonary Deseases "Sv. Sofia", Third Clinic for Non-Sp
  • Sofia, Bulgaria, 1431
    • Uni. Multiprofile Hosp. for Active Treatment-Aleksandrovska
  • Sofia, Bulgaria, 1606
    • Medical Center N.I. Pirogov EOOD
  • Sofia, Bulgaria, 1618
    • Alitera - Med - Medical Center EOOD
  • Stara Zagora, Bulgaria, 6000
    • Medical Center "Nov Rehabilitatsionen Tsentar", EOOD
  • Veliko Tarnovo, Bulgaria, 5000
    • Medical Center Tara OOD
• Canada
  • Ontario
    • Brampton, Ontario, Canada, L6T 0G1
      • Aggarwal And Associates
    • Mississauga, Ontario, Canada, L5A 3V4
      • Cheema Research
    • Toronto, Ontario, Canada, M5T 3A9
      • Inspiration Research
    • Windsor, Ontario, Canada, N8X 5A6
      • Anil Dhar Professional Medicine Corporation
  • Quebec
    • Trois-Rivières, Quebec, Canada, G8T 7A1
      • C.I.C. Mauricie
• Czechia
  • Jindřichův Hradec, Czechia, 377 01
    • MediTrial s.r.o.
  • Ostrava-Poruba, Czechia, 708 00
    • EUC Klinika Ostrava a.s.
  • Strakonice, Czechia, 38601
    • Ordinace pro tuberkulozu a respiracni nemoci
  • Tabor, Czechia, 390 01
    • KASMED s.r.o.
  • Teplice, Czechia, 415 01
    • Alergologie Teplice, s.r.o.
• Germany
  • Geesthacht, Germany, 21502
    • Pneumologisches Forschungsinstitut Hohegeest
  • Leipzig, Germany, 04357
    • POIS Leipzig GbR
  • Mainz, Germany, 55131
    • Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Medizinische Klinik, Pneumologie
  • Münster, Germany, 48149
    • Universitatsklinikum Munster
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
• New Zealand
  • Auckland, New Zealand, 1051
    • Greenlane Clinical Centre
  • Wellington, New Zealand, 6021
    • Medical Research Institute of New Zealand
• Peru
  • Lima, Peru, Lima 41
    • Clinica San Borja
  • Lima, Peru, Lima 1
    • Clinica Internacional
  • Lima, Peru, Lima 27
    • Clinica Ricardo Palma; THORAX
  • Lima, Peru, Lima 21
    • Abk Reuma Srl- Medicentro
  • Lima, Peru, Lima 32
    • Instituto Peruano de Investigacion en Ciencias Medicas
  • Piura, Peru, 20001
    • Hospital Santa Rosa Piura
• Poland
  • Bialystok, Poland, 15-003
    • Centrum Medycyny Oddechowej Robert M. Mróz
  • Krakow, Poland, 30-033
    • Centrum Medyczne All-Med
  • Krakow, Poland, 31-624
    • Malopolskie Centrum Alergologii
  • Kraków, Poland, 31-637
    • Niepubliczny Zaklad Opieki Zdrowotnej Centrum Medyczne ProMiMed sp z o.o. sp.k.
  • Lodz, Poland, 90-153
    • SPZOZ Uniwersytecki Szpital Kliniczny nr 1 im. Norberta Barlickiego Uniwersytetu Medycznego w Lodzi
  • Ostrow Wielkopolski, Poland, 63-400
    • Specjalistyczna Poradnia Pulmonologiczna
  • Radom, Poland, 26-600
    • Przedsiebiorstwo Podmiotu Leczniczego Poradnie Specjalistyczne MAGMED
  • Tarnow, Poland, 33-100
    • ALERGO-MED Specjalistyczna Przychodnia Lekarska Sp. z o. o
  • Wroclaw, Poland, 53-301
    • Ewa Pisarczyk-Bogacka Specjalistyczna Praktyka Lekarska
  • Wroclaw, Poland, 54-239
    • NZOZ Lekarze Specjaliści J. Małolepszy i Partnerzy
• Romania
  • Brasov, Romania, 16
    • Theramed SRL
  • Cluj-Napoca, Romania, 400371
    • Spitalul Clinic de Pneumoftiziologie Leon Daniello Cluj-Napoca, Sectia Clinica Pneumologie I
  • Craiova, Romania, 200515
    • Spitalul Clinic de Boli Infectioase si Pneumoftiziologie Victor Babes Craiova
  • Timisoara, Romania, 300134
    • Fundatia CardioPrevent
  • Timisoara, Romania, 300310
    • Dr. Victor Babes Pneumology and Infectious Diseases Clinical Hospital
• Russian Federation
  • Barnaul, Russian Federation, 656045
    • City Hospital #5
  • Kemerovo, Russian Federation, 650099
    • Municipal Healthcare Institution City Clinical Hospital #3 named after M.A. Podgorbunskogo
  • Moscow, Russian Federation, 115446
    • I.M. Sechenov Moscow State Medical University the Ministry of Health and Social Development of RF
  • Novosibirsk, Russian Federation, 630008
    • Novosibirsk Municipal Clinical Hospital For Emergency Medicine #2
  • Novosibirsk, Russian Federation, 630051
    • City Clinical Hospital #2
  • Ryazan, Russian Federation, 390026
    • Ryazan State Medical University named after I.P.Pavlov
  • St. Petersburg, Russian Federation, 197706
    • City Hospital #40 of Resort Administrative District
  • St. Petersburg, Russian Federation, 197089
    • St. Petersburg State Medical University n.a. I.P. Pavlov
  • St. Petersburg, Russian Federation, 194295
    • Clinic Reavita LLC
  • St. Petersburg, Russian Federation, 195271
    • SHI Ctr Occupational Pathology
  • Tomsk, Russian Federation, 634050
    • Siberian State Medical University
  • Moskovskaja Oblast
    • Yaroslavl, Moskovskaja Oblast, Russian Federation, 150003
      • Clinical Emergency Hospital n.a.N.V. Soloviev
  • Sankt Petersburg
    • Moscow, Sankt Petersburg, Russian Federation, 117574
      • LLC - ABC Medicina
• South Africa
  • Cape Town, South Africa, 7700
    • University of Cape Town Lung Institute; Lung Clinical Research
  • Cape Town, South Africa, 7530
    • Tiervalei Trial Centre
  • Durban, South Africa, 4001
    • St Augustines Hospital; Infectoilogy
  • Durban, South Africa, 4091
    • Vawda Z.Fa Practice
  • Umkomaas, South Africa, 4170
    • Aliwal Shoal Medical Center
• Ukraine
  • Dnepropetrovsk, Ukraine, 49000
    • Public Institution City Clinical Hospital # 6 of Dnipropetrovsk Regional Board
  • Dnipropetrovsk, Ukraine, 49027
    • Ukrainian State Institute of Medical and Social Problems of Disability
  • Ivano-Frankivsk, Ukraine, 76018
    • Regional Phthisiology and Pulmonology Center
  • Kharkiv, Ukraine, 61039
    • SI Institute of Therapy n.a. L.T. Mala of National Academy of Medical Sciences of Ukraine
  • Kyiv, Ukraine, 04107
    • Municipal Institution of Kyiv Regional Council Kyiv Regional Clinical Hospital
  • Kyiv, Ukraine, 03680
    • SI National Institute of Phthisiology and Pulmonology n.a. F.G.Yanovskyi under NAMS of Ukraine
  • Kyiv, Ukraine, 04201
    • Kyiv City Clinical Hospital #8
  • Mykolaiv, Ukraine, 54003
    • City Hospital #1
  • Odesa, Ukraine, 65025
    • Municipal Institution Odesa Regional Clinical Hospital
  • Vinnytsya, Ukraine, 21001
    • Small Business Private Enterprise Medical Centre Pulse
  • Chernihiv Governorate
    • Chernivtsi, Chernihiv Governorate, Ukraine, 58005
      • Regional Municipal Institution Chernivtsi Regional Clinical Hospital
  • KIEV Governorate
    • Kyiv, KIEV Governorate, Ukraine, 02091
      • Kyiv City Tuberculosis Hospital #1; Department of Differential Diagnosis of Lung Diseases
  • Kherson Governorate
    • Zaporizhzhia, Kherson Governorate, Ukraine, 69104
      • Municipal institution; City hospital #1; Department of Therapy
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Alabama Allergy & Asthma
  • Arizona
    • Tucson, Arizona, United States, 85710
      • Del Sol Research Management
  • California
    • Bakersfield, California, United States, 93301
      • Kern Allergy Med Clinic, Inc.
    • Long Beach, California, United States, 90808
      • Allergy & Asthma Care Center of Southern California
    • Los Angeles, California, United States, 90025
      • Jonathan Corren MD, Inc.
    • Los Angeles, California, United States, 90025
      • CA Allergy & Asthma Med Grp; Medical Group, Inc.
    • Los Angeles, California, United States, 90048
      • Office of Robert N Wolfe MD
    • Rancho Mirage, California, United States, 92270
      • Advances in Medicine
    • Redwood City, California, United States, 94063
      • Allergy & Asthma Consultants
    • Stockton, California, United States, 95207
      • Bensch Research Associates
    • Walnut Creek, California, United States, 94598
      • Allergy and Asthma Clinical Research, Inc.
  • Colorado
    • Centennial, Colorado, United States, 80112
      • IMMUNOe Research Centers
    • Colorado Springs, Colorado, United States, 80907
      • Asthma & Allergy; Associates, P.C.
    • Wheat Ridge, Colorado, United States, 80033
      • Western States Clinical Research, Inc
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale University School of Medicine
  • Florida
    • Panama City, Florida, United States, 32405
      • Emerald Coast Research Associates
    • Winter Park, Florida, United States, 32789
      • Florida Premier Research Institute
  • Georgia
    • Stockbridge, Georgia, United States, 30281
      • Atlanta Allergy & Asth Clin PC
  • Idaho
    • Twin Falls, Idaho, United States, 83301
      • Asthma & Allergy of Idaho
  • Maryland
    • Baltimore, Maryland, United States, 21236
      • Asthma, Allergy & Sinus Center
    • Baltimore, Maryland, United States, 21236
      • Chesapeake Clinical Research Inc - CRN
  • Massachusetts
    • Fall River, Massachusetts, United States, 02720
      • Genesis Clinical Research & Consulting, LLC
    • North Dartmouth, Massachusetts, United States, 02747
      • Infinity Medical Research Inc
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Midwest Clinical Research LLC
  • Nebraska
    • Bellevue, Nebraska, United States, 68123
      • The Allergy and Asthma Center
  • New York
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28277
      • American Health Research Inc.
  • Ohio
    • Canton, Ohio, United States, 44718
      • Allergy & Respiratory Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • Integrity People Services Research Company
    • Tulsa, Oklahoma, United States, 74136
      • Vital Prospects Clin Res Pc
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
  • Rhode Island
    • Warwick, Rhode Island, United States, 02865
      • Asthma & Allergy Physicians of Rhode Island Clinical Research Institute (AAPRI CRI)
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Medical Research
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Clinical Research Solutions PC
    • Nashville, Tennessee, United States, 37208
      • Meharry Medical College; Clinical Trials Office
  • Texas
    • Boerne, Texas, United States, 78006
      • TTS Research
    • Dallas, Texas, United States, 75230
      • Elliot J. Ginchansky, MD, PA
    • Houston, Texas, United States, 077099
      • Pioneer Research Solutions
    • McKinney, Texas, United States, 75069
      • Metroplex Pulmonology & Sleep Center
    • San Antonio, Texas, United States, 78229
      • Allergy & Asthma Research Center
  • Utah
    • Murray, Utah, United States, 84107
      • Allergy Associates of Utah
  • Virginia
    • Richmond, Virginia, United States, 23226
      • Commonwealth Clinical Research Specialists
  • Washington
    • Seattle, Washington, United States, 98195
      • Washington Univ School of Med

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MSTT1041A 210 mg; Participants will receive MSTT1041A 210 milligrams (mg), subcutaneously every 4 weeks from randomization through Week 50.	Drug: MSTT1041A; MSTT1041A will be administered as subcutaneous injections.; Other Names: RO7187807
Experimental: MSTT1041A 490 mg; Participants will receive MSTT1041A 490 mg, subcutaneously every 4 weeks from randomization through Week 50.	Drug: MSTT1041A; MSTT1041A will be administered as subcutaneous injections.; Other Names: RO7187807
Experimental: MSTT1041A 70 mg; Participants will receive MSTT1041A 70 mg, subcutaneously every 4 weeks from randomization through Week 50.	Drug: MSTT1041A; MSTT1041A will be administered as subcutaneous injections.; Other Names: RO7187807
Placebo Comparator: Placebo; Participants will receive placebo matched with MSTT1041A, subcutaneously every 4 weeks from randomization through Week 50.	Drug: Placebo; Placebo matched with MSTT1041A.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline to Week 54

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline to Week 54
Time to First Asthma Exacerbation	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.	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.	Week 54
Absolute Change in Patient-Reported Use of Short-Acting Rescue Therapy	Adjusted mean values are all equal to zero.	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.	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.	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.	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.	Baseline
Serum Concentration of Astegolimab (MSTT1041A)		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.	From baseline to the first appearance of ADAs at any point post-baseline (up to Week 54)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Kelsen SG, Agache IO, Soong W, Israel E, Chupp GL, Cheung DS, Theess W, Yang X, Staton TL, Choy DF, Fong A, Dash A, Dolton M, Pappu R, Brightling CE. Astegolimab (anti-ST2) efficacy and safety in adults with severe asthma: A randomized clinical trial. J Allergy Clin Immunol. 2021 Sep;148(3):790-798. doi: 10.1016/j.jaci.2021.03.044. Epub 2021 Apr 16.

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2016
• Primary Completion (Actual): April 5, 2019
• Study Completion (Actual): July 26, 2019

Study Registration Dates

• First Submitted: September 27, 2016
• First Submitted That Met QC Criteria: September 27, 2016
• First Posted (Estimate): September 28, 2016

Study Record Updates

• Last Update Posted (Actual): December 28, 2022
• Last Update Submitted That Met QC Criteria: November 21, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Anti-Infective Agents; Antiviral Agents; Anti-Inflammatory Agents; Tumor Necrosis Factor Inhibitors; Astegolimab
• Other Study ID Numbers: GB39242; 2016-001549-13 (EudraCT Number)