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

Asthma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02918019
• Other study ID #: GB39242
• Secondary ID: 2016-001549-13
• Status: Completed
• Phase: Phase 2
• Start date: September 20, 2016
• Est. completion date: July 26, 2019

Study information

• Verified date: November 2022
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 517
• Est. completion date: July 26, 2019
• Est. primary completion date: April 5, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• MSTT1041A
MSTT1041A will be administered as subcutaneous injections.
• Placebo
Placebo matched with MSTT1041A.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Bulgaria,  Canada,  Czechia,  Germany,  Korea, Republic of,  New Zealand,  Peru,  Poland,  Romania,  Russian Federation,  South Africa,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	Absolute Change in Patient-Reported Use of Short-Acting Rescue Therapy	Adjusted mean values are all equal to zero.	Baseline to Week 54
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Serum Concentration of Astegolimab (MSTT1041A)		Weeks 26 and 54
Secondary	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)