Study of Reslizumab in Participants With Uncontrolled Asthma and Elevated Blood Eosinophils

Asthma Clinical Trial

Official title:

A 52-Week Double-Blind, Placebo-Controlled, Parallel-Group Efficacy and Safety Study of Reslizumab 110 mg Fixed, Subcutaneous Dosing in Patients With Uncontrolled Asthma and Elevated Blood Eosinophils

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02452190
• Other study ID #: C38072-AS-30025
• Secondary ID: 2015-000865-29
• Status: Completed
• Phase: Phase 3
• Start date: September 28, 2015
• Est. completion date: January 31, 2018

Study information

• Verified date: November 2021
• Source: Teva Branded Pharmaceutical Products R&D, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to determine the effect of reslizumab (110 mg) administered subcutaneously every 4 weeks on clinical asthma exacerbations in adults and adolescents with asthma and elevated blood eosinophils who are inadequately controlled on standard-of-care asthma therapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 468
• Est. completion date: January 31, 2018
• Est. primary completion date: December 4, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

• Written informed consent is obtained.
• The participant is male or female, 12 years of age and older, with a diagnosis of asthma.
• The participant has Forced Expiratory Volume in 1 Second (FEV1) reversibility according to standard American Thoracic Society (ATS) or European Respiratory Society (ERS) protocol.
• The participant has required an inhaled corticosteroid.
• The participant has required an additional asthma controller medication besides inhaled corticosteroids.
• The participant has a history of asthma exacerbation.
• The participant must be willing and able to comply with study restrictions, perform requisite procedures and remain at the clinic for the required duration during the study period, and be willing to return to the clinic for the follow-up evaluation as specified in this protocol.
• Additional criteria may apply, please contact the investigator for more information

Exclusion Criteria:

• The participant has any clinically significant, uncontrolled medical condition (treated or untreated) that would interfere with the study schedule or procedures, interpretation of efficacy results, or compromise the patient's safety.
• The participant has another confounding underlying lung disorder
• The participant has a known hypereosinophilic syndrome.
• The participant has a diagnosis of malignancy within 5 years of the screening visit, except for treated and cured non-melanoma skin cancers.
• The participant is a pregnant or lactating woman, or intends to become pregnant during the study. Any woman becoming pregnant during the study will be withdrawn from the study.
• The participant is a current smoker or has a smoking history.
• The participated in a clinical trial within 30 days or 5 half-lives of the investigational drug before screening, whichever is longer.
• The participant was previously exposed to reslizumab.
• The participant has a history of an immunodeficiency disorder including human immunodeficiency virus (HIV).
• The participant has current or suspected drug and alcohol abuse.
• The participant has an active helminthic parasitic infection or was treated for one within 6 months of screening.
• The participant has a history of allergic reaction or hypersensitivity to any component of the study drug.
• Additional criteria may apply, please contact the investigator for more information

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• Reslizumab
Reslizumab will be administered subcutaneously in a dose of 110 mg every 4 weeks.
• Placebo
Matching Placebo

Locations

Country	Name	City	State
Argentina	Teva Investigational Site 20033	Buenos Aires
Argentina	Teva Investigational Site 20035	Buenos Aires
Argentina	Teva Investigational Site 20040	Buenos Aires
Argentina	Teva Investigational Site 20041	Cordoba
Argentina	Teva Investigational Site 20053	Lanus
Argentina	Teva Investigational Site 20037	Mar Del Plata
Argentina	Teva Investigational Site 20036	Mendoza
Argentina	Teva Investigational Site 20032	Rosario
Argentina	Teva Investigational Site 20054	Rosario
Argentina	Teva Investigational Site 20046	San Miguel de Tucuman
Argentina	Teva Investigational Site 20045	San Rafael
Australia	Teva Investigational Site 78085	Bedford Park
Australia	Teva Investigational Site 78083	Nedlands
Australia	Teva Investigational Site 78088	Parkville
Australia	Teva Investigational Site 78087	Sherwood
Australia	Teva Investigational Site 78084	Woolloongabba
Belgium	Teva Investigational Site 37054	Bruxelles
Belgium	Teva Investigational Site 37053	Erpent
Belgium	Teva Investigational Site 37055	Gent
Canada	Teva Investigational Site 11105	Etobicoke	Ontario
Canada	Teva Investigational Site 11106	Vancouver	British Columbia
Canada	Teva Investigational Site 11109	Windsor
Czechia	Teva Investigational Site 54130	Jablonec nad Nisou
Czechia	Teva Investigational Site 54128	Jindrichuv Hradec
Czechia	Teva Investigational Site 54129	Tabor
France	Teva Investigational Site 35182	Strasbourg
France	Teva Investigational Site 35183	Toulouse
Germany	Teva Investigational Site 32559	Bad Worishofen
Germany	Teva Investigational Site 32556	Berlin
Germany	Teva Investigational Site 32561	Berlin
Germany	Teva Investigational Site 32564	Berlin
Germany	Teva Investigational Site 32567	Berlin
Germany	Teva Investigational Site 32570	Berlin
Germany	Teva Investigational Site 32568	Frankfurt
Germany	Teva Investigational Site 32560	Frankfurt am Main
Germany	Teva Investigational Site 32562	Hamburg
Germany	Teva Investigational Site 32566	Hannover
Germany	Teva Investigational Site 32555	Koblenz
Germany	Teva Investigational Site 32557	Leipzig
Germany	Teva Investigational Site 32563	Leipzig
Germany	Teva Investigational Site 32565	Lubeck
Germany	Teva Investigational Site 32551	Mainz
Germany	Teva Investigational Site 32569	Witten
Hungary	Teva Investigational Site 51216	Balassagyarmat
Hungary	Teva Investigational Site 51228	Budapest
Hungary	Teva Investigational Site 51221	Csorna
Hungary	Teva Investigational Site 51220	Debrecen
Hungary	Teva Investigational Site 51223	Debrecen
Hungary	Teva Investigational Site 51255	Dombovar
Hungary	Teva Investigational Site 51218	Godollo
Hungary	Teva Investigational Site 51222	Gyor
Hungary	Teva Investigational Site 51227	Hajdunanas
Hungary	Teva Investigational Site 51226	Kaposvar
Hungary	Teva Investigational Site 51231	Kapuvar
Hungary	Teva Investigational Site 51224	Szazhalombatta
Hungary	Teva Investigational Site 51219	Szeged
Hungary	Teva Investigational Site 51225	Szigetvar
Hungary	Teva Investigational Site 51217	Szombathely
Hungary	Teva Investigational Site 51229	Veszprem
Israel	Teva Investigational Site 80077	Ashkelon
Israel	Teva Investigational Site 80076	Haifa
Israel	Teva Investigational Site 80078	Jerusalem
Israel	Teva Investigational Site 80094	Jerusalem
Israel	Teva Investigational Site 80080	Kfar Saba
Israel	Teva Investigational Site 80073	Petach Tikva
Israel	Teva Investigational Site 80081	Petah Tikva
Israel	Teva Investigational Site 80079	Ramat Gan
Israel	Teva Investigational Site 80075	Rehovot
Japan	Teva Investigational Site 84039	Amagasaki
Japan	Teva Investigational Site 84053	Ginowan
Japan	Teva Investigational Site 84049	Hakodate
Japan	Teva Investigational Site 84034	Hiroshima
Japan	Teva Investigational Site 84036	Kanazawa-shi
Japan	Teva Investigational Site 84037	Kishiwada-shi
Japan	Teva Investigational Site 84044	Kobe
Japan	Teva Investigational Site 84048	Kobe
Japan	Teva Investigational Site 84047	Kodaira
Japan	Teva Investigational Site 84045	Kumamoto
Japan	Teva Investigational Site 84043	Mizunami-shi
Japan	Teva Investigational Site 84041	Sagamihara
Japan	Teva Investigational Site 84031	Tokyo
Japan	Teva Investigational Site 84032	Tokyo
Japan	Teva Investigational Site 84046	Toyama
Japan	Teva Investigational Site 84038	Toyama-shi
Japan	Teva Investigational Site 84035	Toyoake-shi
Japan	Teva Investigational Site 84040	Yokohama-shi
Korea, Republic of	Teva Investigational Site 87015	Bucheon
Korea, Republic of	Teva Investigational Site 87014	Seoul
Korea, Republic of	Teva Investigational Site 87016	Seoul
Mexico	Teva Investigational Site 21084	Guadalajara
Mexico	Teva Investigational Site 21085	Guadalajara
Mexico	Teva Investigational Site 21088	Guadalajara
Mexico	Teva Investigational Site 21089	Guadalajara
Mexico	Teva Investigational Site 21087	Monterrey
Mexico	Teva Investigational Site 21086	Zapopan
New Zealand	Teva Investigational Site 79046	Auckland
New Zealand	Teva Investigational Site 79047	Auckland
Poland	Teva Investigational Site 53310	Bialystok
Poland	Teva Investigational Site 53315	Bialystok
Poland	Teva Investigational Site 53308	Gdansk
Poland	Teva Investigational Site 53311	Krakow
Poland	Teva Investigational Site 53312	Lodz
Poland	Teva Investigational Site 53314	Lodz
Poland	Teva Investigational Site 53313	Poznan
Poland	Teva Investigational Site 53309	Tarnow
Romania	Teva Investigational Site 52108	Brasov
Romania	Teva Investigational Site 52109	Brasov
Romania	Teva Investigational Site 52105	Bucharest
Romania	Teva Investigational Site 52107	Bucharest
Romania	Teva Investigational Site 52104	Cluj-Napoca
Romania	Teva Investigational Site 52111	Deva
Romania	Teva Investigational Site 52106	Targu Mures
Romania	Teva Investigational Site 52110	Timisoara
Russian Federation	Teva Investigational Site 50350	Barnaul
Russian Federation	Teva Investigational Site 50354	Kemerovo
Russian Federation	Teva Investigational Site 50348	Moscow
Russian Federation	Teva Investigational Site 50351	Moscow
Russian Federation	Teva Investigational Site 50347	Novosibirsk
Russian Federation	Teva Investigational Site 50355	Saint Petersburg
Russian Federation	Teva Investigational Site 50352	St. Petersburg
Russian Federation	Teva Investigational Site 50349	Tomsk
South Africa	Teva Investigational Site 90027	Benoni
South Africa	Teva Investigational Site 90028	Bloemfontein
South Africa	Teva Investigational Site 90026	Cape Town
South Africa	Teva Investigational Site 90029	Cape Town
South Africa	Teva Investigational Site 90031	Cape Town
South Africa	Teva Investigational Site 90030	Durban
South Africa	Teva Investigational Site 90032	Durban
Spain	Teva Investigational Site 31149	Barcelona
Spain	Teva Investigational Site 31147	Esplugues de Llobregat
Spain	Teva Investigational Site 31152	Girona
Spain	Teva Investigational Site 31154	Vitoria-Gasteiz
Turkey	Teva Investigational Site 82042	Ankara
Turkey	Teva Investigational Site 82041	Izmir
Turkey	Teva Investigational Site 82040	Kocaeli
Turkey	Teva Investigational Site 82039	Konya
Turkey	Teva Investigational Site 82043	Mersin
Ukraine	Teva Investigational Site 58216	Chernivtsi
Ukraine	Teva Investigational Site 58219	Dnipropetrovsk
Ukraine	Teva Investigational Site 58225	Dnipropetrovsk
Ukraine	Teva Investigational Site 58222	Ivano-Frankivsk
Ukraine	Teva Investigational Site 58213	Kharkiv
Ukraine	Teva Investigational Site 58221	Kharkiv
Ukraine	Teva Investigational Site 58223	Kharkiv
Ukraine	Teva Investigational Site 58227	Kharkiv
Ukraine	Teva Investigational Site 58214	Kremenchuk
Ukraine	Teva Investigational Site 58228	Kryvyi Rih
Ukraine	Teva Investigational Site 58218	Kyiv
Ukraine	Teva Investigational Site 58220	Kyiv
Ukraine	Teva Investigational Site 58226	Kyiv
Ukraine	Teva Investigational Site 58230	Kyiv
Ukraine	Teva Investigational Site 58253	Kyiv
Ukraine	Teva Investigational Site 58234	Sumy
Ukraine	Teva Investigational Site 58233	Vinnytsia
Ukraine	Teva Investigational Site 58229	Vinnytsya
Ukraine	Teva Investigational Site 58231	Zaporizhzhya
Ukraine	Teva Investigational Site 58224	Zhaporizhzhya
United States	Teva Investigational Site 13207	Abingdon	Virginia
United States	Teva Investigational Site 13765	Albany	Georgia
United States	Teva Investigational Site 13185	Arlington	Texas
United States	Teva Investigational Site 13196	Aventura	Florida
United States	Teva Investigational Site 13215	Bakersfield	California
United States	Teva Investigational Site 13769	Belleville	New Jersey
United States	Teva Investigational Site 13242	Bethlehem	Pennsylvania
United States	Teva Investigational Site 13226	Biloxi	Mississippi
United States	Teva Investigational Site 13212	Birmingham	Alabama
United States	Teva Investigational Site 13258	Boys Town	Nebraska
United States	Teva Investigational Site 13249	Buford	Georgia
United States	Teva Investigational Site 13181	Canoga Park	California
United States	Teva Investigational Site 13230	Chicago	Illinois
United States	Teva Investigational Site 13186	Cincinnati	Ohio
United States	Teva Investigational Site 13253	Cleveland	Ohio
United States	Teva Investigational Site 13199	Corsicana	Texas
United States	Teva Investigational Site 13260	Dallas	Texas
United States	Teva Investigational Site 13229	Denver	Colorado
United States	Teva Investigational Site 13209	East Providence	Rhode Island
United States	Teva Investigational Site 13259	Edmond	Oklahoma
United States	Teva Investigational Site 13183	Fairfax	Virginia
United States	Teva Investigational Site 13257	Falls Church	Virginia
United States	Teva Investigational Site 13241	Flagstaff	Arizona
United States	Teva Investigational Site 13256	Fort Lauderdale	Florida
United States	Teva Investigational Site 13254	Fresno	California
United States	Teva Investigational Site 13194	Glendale	Arkansas
United States	Teva Investigational Site 13216	Huntington Beach	California
United States	Teva Investigational Site 13218	Jenkintown	Pennsylvania
United States	Teva Investigational Site 13203	Kissimmee	Florida
United States	Teva Investigational Site 13223	Knoxville	Tennessee
United States	Teva Investigational Site 13191	Lafayette	Louisiana
United States	Teva Investigational Site 13763	Lawrenceville	Georgia
United States	Teva Investigational Site 13225	Lenexa	Kansas
United States	Teva Investigational Site 13217	Lincoln	Rhode Island
United States	Teva Investigational Site 13247	Long Beach	California
United States	Teva Investigational Site 13195	Medford	Oregon
United States	Teva Investigational Site 13197	Miami	Florida
United States	Teva Investigational Site 13220	Miami	Florida
United States	Teva Investigational Site 13243	Miami	Florida
United States	Teva Investigational Site 13202	Michigan City	Indiana
United States	Teva Investigational Site 13205	Napa	California
United States	Teva Investigational Site 13188	New Hyde Park	New York
United States	Teva Investigational Site 13233	New Port Richey	Florida
United States	Teva Investigational Site 13232	New York	New York
United States	Teva Investigational Site 13767	New York	New York
United States	Teva Investigational Site 13211	Normal	Illinois
United States	Teva Investigational Site 13200	North Dartmouth	Massachusetts
United States	Teva Investigational Site 13210	Ocean City	New Jersey
United States	Teva Investigational Site 13238	Oklahoma City	Oklahoma
United States	Teva Investigational Site 13201	Orlando	Florida
United States	Teva Investigational Site 13250	Orlando	Florida
United States	Teva Investigational Site 13222	Owensboro	Kentucky
United States	Teva Investigational Site 13246	Pembroke Pines	Florida
United States	Teva Investigational Site 13189	Philadelphia	Pennsylvania
United States	Teva Investigational Site 13190	Pittsburgh	Pennsylvania
United States	Teva Investigational Site 13187	Provo	Utah
United States	Teva Investigational Site 13239	Richmond	Virginia
United States	Teva Investigational Site 13204	Saint Louis	Missouri
United States	Teva Investigational Site 13224	San Antonio	Texas
United States	Teva Investigational Site 13764	San Jose	California
United States	Teva Investigational Site 13235	Shiloh	Illinois
United States	Teva Investigational Site 13227	Spokane	Washington
United States	Teva Investigational Site 13252	Stockton	California
United States	Teva Investigational Site 13208	Tallahassee	Florida
United States	Teva Investigational Site 13255	Tampa	Florida
United States	Teva Investigational Site 13240	Toledo	Ohio
United States	Teva Investigational Site 13184	Waco	Texas
United States	Teva Investigational Site 13251	Walnut Creek	California
United States	Teva Investigational Site 13766	Waterbury	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Teva Branded Pharmaceutical Products R&D, Inc.	PPD

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Canada,  Czechia,  France,  Germany,  Hungary,  Israel,  Japan,  Korea, Republic of,  Mexico,  New Zealand,  Poland,  Romania,  Russian Federation,  South Africa,  Spain,  Turkey,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Clinical Asthma Exacerbations (CAEs) During 52 Weeks of Treatment	A CAE was defined as a clinically-judged deterioration in asthma control, as determined by the investigator and as evidenced by new or worsening asthma signs or symptoms based on the participant's history, asthma control diary, physical examination, and/or ambulatory or clinic visit assessment of lung function and that resulted in a medical intervention, including at least 1 of the following: 1) use of systemic corticosteroids (oral or injection) or at least a doubling from a stable maintenance oral corticosteroid dose for at least 3 days; 2) asthma-specific hospital admission; 3) asthma-specific emergency department visit. Adjusted CAE rate and confidence intervals were based on Negative Binomial regression model adjusted for stratification factors. Results are presented as adjusted means. For this analysis, the offset variable is calculated as the logarithm of treatment duration minus the summed duration of exacerbations during the treatment period.	Day 1 to Week 52
Secondary	Change From Baseline to Week 52 in Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1)	Change in pre-bronchodilator FEV1 from baseline to week 52 is presented. FEV1 is a standard measurement of air movement in the lungs of participants with asthma obtained from pulmonary function tests. It is the volume of air expired in the first second of a forced expiration using a spirometer.; Analysis of the change from baseline to each visit was performed using a mixed effect model for repeated measures (MMRM) including fixed effects for treatment, visit, treatment by visit interaction, age group, blood eosinophil counts at enrollment, and sex, height and baseline value as covariates, and participant as a random effect.	Baseline, Week 52
Secondary	Change From Baseline to Week 52 in Asthma Quality of Life Questionnaire for Participants 12 Years and Older (AQLQ+12) Score	AQLQ is a 32-item instrument administered as a self-assessment. AQLQ+12 is a modified version of AQLQ developed to measure functional impairments of participants aged 12-70 years. It is divided into 4 domains: activity limitation, symptoms, emotional function, and environmental stimuli. Participants were asked to recall their experiences during the last 2 weeks and respond to each question on a 7-point scale (1=severe impairment, 7=no impairment), where higher scores indicated "better quality of life." Overall AQLQ+12 score is the mean of all 32 responses. Analysis of the change from baseline to each visit was performed using a MMRM including fixed effects for treatment, visit, treatment by visit interaction, age group, blood eosinophil counts at enrollment, and sex, height and baseline value as covariates, and participant as a random effect.	Baseline, Week 52
Secondary	Change From Baseline to Week 52 in 6-item Asthma Control Questionnaire (ACQ-6) Score	The ACQ-6 is a 6-item validated asthma assessment tool that has been widely used. Six questions are self-assessments (completed by the participant), 5 questions assessing asthma symptoms: night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing, and 1 question for short-acting bronchodilator use. Each item on the ACQ-6 has a possible score ranges from 0 to 6, and the total score is the mean of all responses. The total score ranging from 0-6 (0=totally controlled and 6=severely uncontrolled). A higher score indicated poorer asthma control. Analysis of the change from baseline to each visit was performed using a mixed effect model for repeated measures (MMRM) including fixed effects for treatment, visit, treatment by visit interaction, age group, blood eosinophil counts at enrollment, and sex, height and baseline value as covariates, and participant as a random effect.	Baseline, Week 52
Secondary	Change From Baseline to Week 52 in Total Asthma Symptom Scores (Day and Night)	Asthma symptoms were recorded by participant each day and night in an asthma control diary. Night score was assessed on a 5-point scale where 0=no symptoms, slept through night, to 4=bad night, no sleep. Day score was assessed on a 6-point scale where 0=very well, no symptoms, to 5= asthma very severe, unable to carry out daily activities. Total asthma symptom score was calculated by taking the sum of the night and day asthma symptom scores recorded, ranging from 0 (no symptom) to 9 (severe symptom). A lower symptom score indicated a better outcome. Analysis of the change from baseline to each visit was performed using a MMRM including fixed effects for treatment, visit, treatment by visit interaction, age group, blood eosinophil counts at enrollment, and sex, height and baseline value as covariates, and participant as a random effect.	Baseline, Week 52
Secondary	Percentage of Asthma Control Days	The percentage of asthma control days over 52 weeks of treatment is presented. An asthma control day was defined as a day on which the participant used less than or equal to 2 puffs of inhaled short-acting beta-agonist, had no nighttime awakenings, and experienced no asthma exacerbations. Analysis of the change from baseline to each visit was performed using a mixed effect MMRM including fixed effects for treatment, visit, treatment by visit interaction, age group, blood eosinophil counts at enrollment, and sex, height and baseline value as covariates, and participant as a random effect.	Day 1 to Week 52
Secondary	Change From Baseline to Week 32 in St. George's Respiratory Questionnaire (SGRQ) Total Score	The SGRQ is a 17-item questionnaire with 50 weighted responses. It provides a total score and three component scores: Symptoms (distress caused by respiratory symptoms), Activity (physical activities that cause or are limited by breathlessness), and Impacts (social and psychological effects of the disease). The total score and each of the SGRQ subscores are scored from 0 to 100 where 0 indicates best and 100 indicates worst health. An increase in score indicates worsening health. Analysis of the change from baseline to each visit was performed using a mixed effect model for repeated measures (MMRM) including fixed effects for treatment, visit, treatment by visit interaction, age group, blood eosinophil counts at enrollment, and sex, height and baseline value as covariates, and participant as a random effect.	Baseline, Week 32
Secondary	Kaplan-Meier (K-M) Estimate of Probability (Percent [%]) of Not Experiencing a CAE by Week 52	CAE was defined as a clinically judged deterioration in asthma control, as determined by the investigator and as evidenced by new or worsening asthma signs or symptoms based on the participant's history, asthma control diary, physical examination, and/or ambulatory or clinic visit assessment of lung function and that resulted in a medical intervention, including at least 1 of the following: 1) use of systemic corticosteroids (oral or injection) or at least a doubling from a stable maintenance oral corticosteroid dose for at least 3 days; 2) asthma-specific hospital admission; 3) asthma-specific emergency department visit.; The KM method was used to estimate and compare the distributions of time to first CAE between treatment groups. Participants without an event during the treatment period were censored at either the date of the end of treatment (Week 52) visit for participants who completed treatment or at the date of last dose (+4 weeks) for participants who discontinued early.	Day 1 to Week 52
Secondary	Number of CAEs Requiring Hospitalization and/or Emergency Department Visits During 52 Weeks of Treatment	A CAE was defined as a clinically judged deterioration in asthma control, as determined by the investigator and as evidenced by new or worsening asthma signs or symptoms based on the participant's history, asthma control diary, physical examination, and/or ambulatory or clinic visit assessment of lung function and that resulted in a medical intervention, including at least 1 of the following: 1) use of systemic corticosteroids (oral or injection) or at least a doubling from a stable maintenance oral corticosteroid dose for at least 3 days; 2) asthma-specific hospital admission; 3) asthma-specific emergency department visit. The frequency of CAEs over 52-week treatment period is expressed as adjusted CAEs rate in 52 weeks. Adjusted CAE rate and confidence intervals were based on Negative Binomial regression model adjusted for stratification factors (age group, blood eosinophil group) and number of prior exacerbations, and an offset variable.	Day 1 to Week 52
Secondary	Number of Moderate Exacerbations During 52 Weeks of Treatment	A moderate exacerbation was defined as a clinically judged deterioration in asthma control as determined by investigator and as evidenced by new or worsening asthma signs or symptoms based on the participant's history, asthma control diary, physical examination, and/or ambulatory or clinic visit assessment of lung function and that resulted in a medical intervention requiring additional asthma controller medication that was not a systemic corticosteroid and did not result in an asthma-specific hospitalization or emergency department visit (that is, a medical intervention that did not otherwise meet the criteria for primary endpoint). Frequency of moderate exacerbations over 52-week treatment period is expressed as adjusted exacerbation rate in 52 weeks. Adjusted exacerbation rate and confidence intervals were based on Negative Binomial regression model adjusted for stratification factors (age group, blood eosinophil group) and number of prior exacerbations, and an offset variable.	Day 1 to Week 52