A Study to Evaluate the Efficacy and Safety of Reslizumab (3.0 mg/kg) in the Reduction of Clinical Asthma Exacerbations in Patients (12-75 Years of Age) With Eosinophilic Asthma

Eosinophilic Asthma Clinical Trial

Official title:

A 12-Month, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Reslizumab (3.0 mg/kg) in the Reduction of Clinical Asthma Exacerbations in Patients (12-75 Years of Age) With Eosinophilic Asthma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01287039
• Other study ID #: C38072/3082
• Status: Completed
• Phase: Phase 3
• Start date: April 2011
• Est. completion date: March 2014

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

This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy, safety, and immunogenicity of treatment with reslizumab in patients with eosinophilic asthma.

Description:

Demonstrate the efficacy of reslizumab, at a dose of 3 mg/kg administered iv every 4 weeks over 12 months, as assessed by the reduction in frequency of clinical asthma exacerbations (CAEs) during 12 months.

An exacerbation event will be considered a CAE if the patient meets either or both of the criteria listed below and this is corroborated with at least 1 other measurement to indicate the worsening of clinical signs and symptoms of asthma:

• use of systemic, or an increase in the use of inhaled, corticosteroid treatment for 3 or more days

• asthma-related emergency treatment The above criteria must be corroborated with at least 1 other measurement to indicate worsening in the clinical signs and symptoms of asthma.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 489
• Est. completion date: March 2014
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 75 Years

Eligibility

Inclusion Criteria:

• The patient is male or female, 12 through 75 years of age, with a previous diagnosis of asthma.

• The patient has had at least 1 asthma exacerbation requiring oral, intramuscular (im), or intravenous (iv) corticosteroid use for at least 3 days over the past 12 months before screening.

• The patient has a current blood eosinophil level of at least 400/µl.

• The patient has airway reversibility of at least 12% to beta-agonist administration.

• The patient has an ACQ score of at least 1.5 at the screening and baseline (before the 1st dose of study drug) visits.

• The patient is taking inhaled fluticasone at a dosage of at least 440 µg, or equivalent, daily. Chronic oral corticosteroid use (no more than 10 mg/day prednisone or equivalent) is allowed. If a patient is on a stable dose, eg, 2 weeks or more of oral corticosteroid treatment at the time of study enrollment, the patient must remain on this dose throughout the study. The patient's baseline asthma therapy regimen (including but not limited to inhaled corticosteroids, oral corticosteroids up to a maximum of 10 mg of prednisone daily or equivalent, leukotriene antagonists, 5-lipooxygenase inhibitors, or cromolyn) must be stable for 30 days prior to screening and baseline, and must continue without dosage changes throughout study.

• All female patients must be surgically sterile, 2 years postmenopausal, or must have a negative pregnancy test ß-human chorionic gonadotropin [ß-HCG]) at screening (serum) and baseline (urine).

• Female patients of childbearing potential (not surgically sterile or 2 years postmenopausal), must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study and for 30 days after participation in the study.

• Written informed consent is obtained. Patients 12 through 17 years old must provide assent.

• The patient is in reasonable health (except for diagnosis of asthma) as judged by the investigator, and as determined by a medical history, medical examination, ECG evaluation (at screening), serum chemistry, hematology, and urinalysis.

• Other criteria apply; please contact the investigator for more information.

Exclusion Criteria:

• The patient has a clinically meaningful co-morbidity that would interfere with the study schedule or procedures, or compromise the patient's safety.

• The patient has known hypereosinophilic syndrome.

• The patient has another confounding underlying lung disorder (eg, chronic obstructive pulmonary disease, pulmonary fibrosis, or lung cancer). Patients with pulmonary conditions with symptoms of asthma and blood eosinophilia (eg, Churg-Strauss syndrome, allergic bronchopulmonary aspergillosis) will also be excluded.

• The patient is a current smoker (ie, has smoked within the last 6 months prior to screening).

• The patient is using systemic immunosuppressive or immunomodulating or other biologic agents (including, but not limited to, anti-IgE mAb, methotrexate, cyclosporin, interferon-a, or anti-tumor necrosis factor [anti TNF] mAb) within 6 months prior to screening.

• The patient has previously received an anti-hIL-5 monoclonal antibody (eg, reslizumab, mepolizumab, or benralizumab).

• The patient has any aggravating medical factors that are inadequately controlled (eg, rhinitis, gastroesophageal reflux disease, and uncontrolled diabetes).

• The patient has participated in any investigative drug or device study within 30 days prior to screening.

• The patient has participated in any investigative biologics study within 6 months prior to screening.

• Female patients who are pregnant, nursing, or, if of childbearing potential, and not using a medically accepted, effective method of birth control (eg, barrier method with spermicide, abstinence, IUD, or steroidal contraceptive [oral, transdermal, implanted, and injected]) are excluded from this study. NOTE: Partner sterility alone is not considered an acceptable form of birth control.

• Other criteria apply; please contact the investigator for more information.

Related Conditions & MeSH terms

• Asthma
• Eosinophilic Asthma
• Pulmonary Eosinophilia

Intervention

Drug:
• Reslizumab
Patients were administered intravenously over 15 to 30 minutes reslizumab at a dosage of 3.0 mg/kg at baseline and once every 4 weeks relative to baseline over 48 weeks for a total of 13 doses.
• Placebo
Matching placebo (20 mM sodium acetate, 7% sucrose), administered intravenously (iv) once every 4 weeks over 52 weeks, for a total of 13 doses administered. Each patient received a specific volume of placebo to match the volume of reslizumab on the basis of the patient's body weight.

Locations

Country	Name	City	State
Australia	Teva Investigational Site 641	Clayton
Australia	Teva Investigational Site 644	Daw Park
Australia	Teva Investigational Site 642	Frankston
Australia	Teva Investigational Site 645	Liverpool
Australia	Teva Investigational Site 643	Nedlands	Western Australia
Belgium	Teva Investigational Site 261	Bruxelles
Belgium	Teva Investigational Site 264	Bruxelles
Belgium	Teva Investigational Site 260	Gent
Belgium	Teva Investigational Site 262	Jambes
Belgium	Teva Investigational Site 263	Liège
Chile	Teva Investigational Site 160	Rancagua
Chile	Teva Investigational Site 163	Santiago
Chile	Teva Investigational Site 164	Santiago
Chile	Teva Investigational Site 165	Santiago
Chile	Teva Investigational Site 161	Temuco
Chile	Teva Investigational Site 162	Valdivia
Chile	Teva Investigational Site 166	Valparaiso
Colombia	Teva Investigational Site 185	Bogota
Colombia	Teva Investigational Site 181	Bogotá
Colombia	Teva Investigational Site 182	Cali
Colombia	Teva Investigational Site 180	Floridablanca
Czechia	Teva Investigational Site 284	Breclav
Czechia	Teva Investigational Site 287	Brno
Czechia	Teva Investigational Site 286	Liberec
Czechia	Teva Investigational Site 280	Olomouc
Czechia	Teva Investigational Site 281	Olomouc
Czechia	Teva Investigational Site 285	Olomouc
Czechia	Teva Investigational Site 283	Tabor
Denmark	Teva Investigational Site 301	Hvidovre
Denmark	Teva Investigational Site 300	Odense
Hungary	Teva Investigational Site 401	Balassagyarmat
Hungary	Teva Investigational Site 400	Miskolc
Hungary	Teva Investigational Site 404	Mosonmagyaróvár
Hungary	Teva Investigational Site 403	Sopron
Hungary	Teva Investigational Site 405	Törökbálint
Israel	Teva Investigational Site 423	Ashkelon
Israel	Teva Investigational Site 430	Beer-Sheva
Israel	Teva Investigational Site 431	Haifa
Israel	Teva Investigational Site 432	Haifa
Israel	Teva Investigational Site 425	Jerusalem
Israel	Teva Investigational Site 428	Jerusalem
Israel	Teva Investigational Site 429	Jerusalem
Israel	Teva Investigational Site 426	Kfar Saba
Israel	Teva Investigational Site 422	Petach Tikva
Israel	Teva Investigational Site 427	Ramat Gan
Israel	Teva Investigational Site 433	Ramat Gan
Israel	Teva Investigational Site 421	Rehovot
Israel	Teva Investigational Site 420	Tel-Aviv
Malaysia	Teva Investigational Site 705	Batu Caves
Malaysia	Teva Investigational Site 700	Kuala Lumpur
Malaysia	Teva Investigational Site 702	Kuala Lumpur
Malaysia	Teva Investigational Site 703	Kuantan
Malaysia	Teva Investigational Site 701	Penang
Malaysia	Teva Investigational Site 704	Taiping
New Zealand	Teva Investigational Site 723	Auckland
New Zealand	Teva Investigational Site 722	Christchurch
New Zealand	Teva Investigational Site 726	Christchurch
New Zealand	Teva Investigational Site 724	Dunedin
New Zealand	Teva Investigational Site 727	Hamilton
New Zealand	Teva Investigational Site 720	Tauranga
New Zealand	Teva Investigational Site 721	Wellington
Philippines	Teva Investigational Site 744	Governor Mangubat Drive, Dasma
Philippines	Teva Investigational Site 742	Manila
Philippines	Teva Investigational Site 740	Quezon City
Philippines	Teva Investigational Site 741	Quezon City
Philippines	Teva Investigational Site 743	Quezon City
Philippines	Teva Investigational Site 745	Quezon City
Poland	Teva Investigational Site 507	Bialystok
Poland	Teva Investigational Site 509	Bydgoszcz
Poland	Teva Investigational Site 501	Bystra
Poland	Teva Investigational Site 500	Ostrow Wielkopolski
Poland	Teva Investigational Site 511	Poznan
Poland	Teva Investigational Site 502	Sopot
Poland	Teva Investigational Site 504	Tarnow
Russian Federation	Teva Investigational Site 545	Barnaul
Russian Federation	Teva Investigational Site 551	Kazan
Russian Federation	Teva Investigational Site 549	Kemerovo
Russian Federation	Teva Investigational Site 550	Nizhniy Novgorod
Russian Federation	Teva Investigational Site 553	Novosibirsk
Russian Federation	Teva Investigational Site 555	Novosibirsk
Russian Federation	Teva Investigational Site 542	St. Petersburg
Russian Federation	Teva Investigational Site 552	Tomsk
Russian Federation	Teva Investigational Site 546	Yaroslavl
South Africa	Teva Investigational Site 581	Cape Town
South Africa	Teva Investigational Site 584	Cape Town
South Africa	Teva Investigational Site 586	Cape Town
South Africa	Teva Investigational Site 587	Centurion
South Africa	Teva Investigational Site 582	Durban
South Africa	Teva Investigational Site 585	Durban
South Africa	Teva Investigational Site 580	Johannesburg
South Africa	Teva Investigational Site 589	Johannesburg
South Africa	Teva Investigational Site 583	Pretoria
South Africa	Teva Investigational Site 588	Pretoria
Sweden	Teva Investigational Site 602	Göteborg
Sweden	Teva Investigational Site 604	Göteborg
Sweden	Teva Investigational Site 603	Linköping
Sweden	Teva Investigational Site 601	Malmö
Thailand	Teva Investigational Site 780	Bangkok
Thailand	Teva Investigational Site 782	Bangkok
Thailand	Teva Investigational Site 783	Bangkok
Thailand	Teva Investigational Site 781	Muang
Thailand	Teva Investigational Site 784	Nakhon Ratchasima
United States	Teva Investigational Site 66	Altoona	Pennsylvania
United States	Teva Investigational Site 63	Boerne	Texas
United States	Teva Investigational Site 51	Boston	Massachusetts
United States	Teva Investigational Site 64	Boys Town	Nebraska
United States	Teva Investigational Site 60	Bronx	New York
United States	Teva Investigational Site 31	Cincinnati	Ohio
United States	Teva Investigational Site 34	Colorado Springs	Colorado
United States	Teva Investigational Site 62	Columbus	Ohio
United States	Teva Investigational Site 52	DeBary	Florida
United States	Teva Investigational Site 72	Houston	Texas
United States	Teva Investigational Site 49	Lexington	Kentucky
United States	Teva Investigational Site 61	Los Angeles	California
United States	Teva Investigational Site 65	Louisville	Kentucky
United States	Teva Investigational Site 33	Madison	Wisconsin
United States	Teva Investigational Site 55	Miami	Florida
United States	Teva Investigational Site 35	Missoula	Montana
United States	Teva Investigational Site 32	Nashville	Tennessee
United States	Teva Investigational Site 50	Oklahoma City	Oklahoma
United States	Teva Investigational Site 37	Orange	California
United States	Teva Investigational Site 38	Richmond	Virginia
United States	Teva Investigational Site 68	Rochester	New York
United States	Teva Investigational Site 74	Saint Louis	Missouri
United States	Teva Investigational Site 56	San Diego	California
United States	Teva Investigational Site 58	Scottsdale	Arizona
United States	Teva Investigational Site 18	Valrico	Florida
United States	Teva Investigational Site 30	Winston-Salem	North Carolina

Sponsors (1)

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

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Chile,  Colombia,  Czechia,  Denmark,  Hungary,  Israel,  Malaysia,  New Zealand,  Philippines,  Poland,  Russian Federation,  South Africa,  Sweden,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of Clinical Asthma Exacerbations (CAEs) During 12 Months of Treatment	An exacerbation event was considered a CAE if the patient met either or both of the criteria listed below and this was corroborated with at least 1 other measurement to indicate the worsening of clinical signs and symptoms of asthma: use of systemic, or an increase in the use of inhaled, corticosteroid treatment for 3 or more days; or an increased 2 or more fold for at least 3 or more days for patient's already on corticosteroids.; asthma-related emergency treatment, such as an unscheduled visit to the physician's office or emergency room for nebulizer treatment or other urgent treatment to prevent worsening of asthma symptoms, or an asthma-related hospitalization CAEs were adjudicated by committee to assure consistency.; Adjusted CAE rate and confidence intervals were based on Negative Binomial regression model adjusted for stratification factors.; Results are offered as adjusted means.	Day 1 to Week 52
Primary	Frequency of Each of the Two Criteria for Clinical Asthma Exacerbations (CAEs)	An exacerbation event was considered a CAE if the patient met either or both of the criteria listed below and this was corroborated with at least 1 other measurement to indicate the worsening of clinical signs and symptoms of asthma: use of systemic, or an increase in the use of inhaled, corticosteroid treatment for 3 or more days; or an increased 2 or more fold for at least 3 or more days for patient's already on corticosteroids.; asthma-related emergency treatment, such as an unscheduled visit to the physician's office or emergency room for nebulizer treatment or other urgent treatment to prevent worsening of asthma symptoms, or an asthma-related hospitalization.; CAEs were adjudicated by committee to assure consistency. Adjusted CAE rate and confidence intervals for the two criteria were based on Negative Binomial regression model adjusted for stratification factors.; Results are offered as adjusted means.	Day 1 to Week 52
Secondary	Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Over 16 Weeks Using Mixed Model for Repeated Measures	FEV1 is a standard measurement of air movement in the lungs of patients 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. Positive change from baseline scores indicate improvement in asthma control.; The during treatment (Weeks 4, 8, 12 and 16) average FEV1 was estimated using a mixed-effect model for repeated measures (MMRM) with fixed effects (treatment, stratification factors, sex, visit, interaction of treatment and visit), covariates (height, baseline value), and patient as the random effect for the repeated measurements.	Day 1 (baseline, pre-dose), Weeks 4, 8, 12 and 16
Secondary	Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) to Week 16	The AQLQ is a 32-item instrument administered as a self-assessment (Juniper et al 1992). The questionnaire is divided into 4 domains: activity limitation, symptoms, emotional function, and environmental stimuli. Patients were asked to recall their experiences during the last 2 weeks and to respond to each question on a 7-point scale (1=severe impairment, 7=no impairment). The overall AQLQ score is the mean of all 32 responses. Five of the activity questions were "patient-specific," which means that each patient identified and scored 5 activities in which the patient was limited by asthma; these 5 activities were identified at the first visit and retained for all subsequent follow-up visits.; Positive change from baseline scores indicate improvement in quality of life.	Day 1 (baseline, pre-dose), Week 16
Secondary	Change From Baseline in Asthma Control Questionnaire (ACQ) Over 16 Weeks Using Mixed Model for Repeated Measures	The ACQ is a 7-item instrument that measures asthma control (Juniper et al 1999). Six questions are self-assessments; the seventh item, completed by a member of the study staff, is the result of the patient's FEV1 measurement. Each item has 7 possible answers on a scale of 0 to 6, and the total score is the mean of all responses (the total scale is therefore 0-6). A higher score is an indication of poorer asthma control. The during treatment (Weeks 4, 8, 12 and 16) average ACQ was estimated using a mixed-effect model for repeated measures (MMRM) with fixed effects (treatment, stratification factors, sex, visit, interaction of treatment and visit), covariates (height, baseline value), and patient as the random effect for the repeated measurements.; Negative change from baseline scores indicate improvement in asthma control.	Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16
Secondary	Kaplan-Meier Estimates for Time to First Clinical Asthma Exacerbation (CAE)	An exacerbation event was considered a CAE if the patient met either or both of the criteria listed below and this was corroborated with at least 1 other measurement to indicate the worsening of clinical signs and symptoms of asthma: use of systemic, or an increase in the use of inhaled, corticosteroid treatment for 3 or more days; or an increased 2 or more fold for at least 3 or more days for patient's already on corticosteroids.; asthma-related emergency treatment, such as an unscheduled visit to the physician's office or emergency room for nebulizer treatment or other urgent treatment to prevent worsening of asthma symptoms, or an asthma-related hospitalization.; CAEs were adjudicated by committee to assure consistency. The distributions were compared by a log rank test stratified by baseline usage of oral corticosteroid (yes or no) and geographical region (US or other).	Day 1 to Day 478 (longest treatment time plus 2 weeks)
Secondary	Change From Baseline in Asthma Symptom Utility Index (ASUI) Over 16 Weeks Using Mixed Model for Repeated Measures	The ASUI is an 11-item instrument designed to assess the frequency and severity of asthma symptoms and side effects, weighted by patient preferences (Revicki et al 1998). ASUI is a utility score that ranges from 0 to 1, with higher values indicating better asthma control; info obtained from questionnaire about asthma symptoms.; The during treatment (Weeks 4, 8, 12 and 16) average ASUI was estimated using a mixed-effect model for repeated measures (MMRM) with fixed effects (treatment, stratification factors, sex, visit, interaction of treatment and visit), covariates (height, baseline value), and patient as the random effect for the repeated measurements.; Positive change from baseline values indicate improvement in asthma symptoms. Information was obtained from questionnaire about asthma symptoms.	Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16
Secondary	Change From Baseline in Short-Acting Beta-Agonist (SABA) Use Over 16 Weeks Using Mixed Model for Repeated Measures	SABA are used for quick relief of asthma symptoms. To measure SABA use, at each clinical visit patients were asked to recall their usage of SABA therapy within the last 3 days of the scheduled visit. If usage was confirmed, the number of puffs used was recorded. For the purpose of summaries, an average daily usage was evaluated by dividing the total number of puffs recorded over 3 days by 3.; The during treatment (Weeks 4, 8, 12 and 16) SABA use was estimated using a mixed-effect model for repeated measures (MMRM) with fixed effects (treatment, stratification factors, sex, visit, interaction of treatment and visit), covariates (height, baseline value), and patient as the random effect for the repeated measurements.; Negative change from baseline scores indicate improvement in asthma control.	Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16
Secondary	Change From Baseline in Blood Eosinophil Count Over 16 Weeks and 52 Weeks Using Mixed Model for Repeated Measures	Blood eosinophil counts were measured using a standard complete blood count (CBC) with differential blood test at each scheduled visit, and from all patients experiencing a serious adverse event, an adverse event leading to withdrawal, or an exacerbation of asthma symptoms.; The during treatment average eosinophil counts were estimated using a mixed-effect model for repeated measures (MMRM) with fixed effects (treatment, stratification factors, sex, visit, interaction of treatment and visit), covariates (height, baseline value), and patient as the random effect for the repeated measurements.; Negative change from baseline values correlate to reduced asthma severity.	Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 or early withdrawal
Secondary	Participants With Treatment-Emergent Adverse Events	An adverse event was defined in the protocol as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an inability to carry out usual activities. Relation of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes.	Day 1 (post-dose) to Week 65. The last postbaseline value for approximately 20 patients in each
Secondary	Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values	Data represents participants with potentially clinically significant (PCS) abnormal serum chemistry, hematology, and urinalysis values.; Significance criteria: Blood urea nitrogen: >=10.71 mmol/L; Uric acid: M>=625, F>=506 µmol/L; Aspartate aminotransferase: >=3*upper limit of normal (ULN). Normal range is 10-43 U/L; Alanine aminotransferase: >=3*ULN. Normal range is 10-40 U/L; GGT = gamma-glutamyl transpeptidase: >= 3*ULN. Normal range is 5-49 U/L.; Bilirubin: >=34.2 µmol/L; White blood cells: <=3.0 or >20 10^9/L; Hemoglobin: M<=115, F<=95 g/dL; Hematocrit: M<0.37, F<0.32 L/L; Neutrophils: <=1.0 10^9/L; Eosinophils: >10.0 %; Platelets: <75 or >=700 10^9/L; Urinalysis: blood, glucose, ketones and total protein: >=2 unit increase from baseline	Week 4 to Week 65. The last postbaseline value for approximately 20 patients in each
Secondary	Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values	Data represents participants with potentially clinically significant (PCS) vital sign values.; Significance criteria; Sitting pulse - high 12-17 yr: >100 and increase of >= 30 beats/minute (bpm); Sitting pulse - low >=18 yr: <50 and decrease of >=30 bpm; Sitting pulse - high >=18 yr: >100 and increase of >=30 bpm; Sitting systolic blood pressure - low >=18 yr: <90 and decrease of >=30 mmHg; Sitting systolic blood pressure - high >=18 yr: >160 and increase of >=30 mmHg; Sitting diastolic blood pressure - low 12-17 yr: <55 and decrease of >=12 mmHg; Sitting diastolic blood pressure - low >=18 yr: <50 and decrease of >=12 mmHg; Sitting diastolic blood pressure - high >=18 yr: >100 and increase of >=12 mmHg; Respiratory rate >=18 yr: >24 and increase of >=10 breaths/minute; Body temperature - low 12-17 yr: <96.5° Fahrenheit or <35.8° Celsius; Body temp - low >=18 yr: <96.5° F or <35.8° C; Body temp - high >=18 yr: >100.5° Fahrenheit	Week 4 to Week 65. The last postbaseline value for approximately 20 patients in each
Secondary	Participants With a Positive Anti-Reslizumab Antibody Status During Study	The immunogenicity of reslizumab was assessed by measuring for the presence of anti-reslizumab antibodies at baseline, weeks 16, 32, 48, and 52 or early withdrawal. Blood samples for anti-reslizumab antibodies assessment were also obtained from all patients (inside or outside of the US) experiencing a serious adverse event, an adverse event leading to withdrawal, or an exacerbation of asthma symptoms.	Weeks 16, 32, 48 and 52