Trial Outcomes & Findings for 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 (NCT NCT01287039)

Last Updated: 2021-11-09

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

489 participants

Primary outcome timeframe

Day 1 to Week 52

Results posted on

2021-11-09

Participant Flow

A total of 1486 patients were screened at 121 centers. Of the 1486 patients screened, 489 patients with asthma and blood eosinophils ≥400/ μL at 102 centers in 17 countries were randomly assigned to double-blind treatment.

997 of 1486 screened patients were not randomized: 888 were excluded on the basis of not meeting inclusion criteria, 23 withdrew consent, 17 had an adverse event during the screening period, 12 met an exclusion criterion, 7 were lost to follow-up and 50 were excluded for other reasons. One placebo patient was randomized but not treated.

Participant milestones

Participant milestones
Measure	Placebo Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.	Reslizumab 3.0 mg/kg Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.
Overall Study STARTED	244	245
Overall Study COMPLETED	215	218
Overall Study NOT COMPLETED	29	27

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.	Reslizumab 3.0 mg/kg Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.
Overall Study Noncompliance with study procedures	0	1
Overall Study Change of location/residence	0	3
Overall Study Elective surgery	0	1
Overall Study Protocol Violation	2	3
Overall Study Excluded medication taken	1	0
Overall Study Noncompliance with study medication	0	1
Overall Study Problem with travel	0	1
Overall Study Death	1	0
Overall Study Change of residence	1	0
Overall Study Adverse Event	7	4
Overall Study Withdrawal by Subject	14	11
Overall Study Lost to Follow-up	3	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=244 Participants Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.	Reslizumab 3.0 mg/kg n=245 Participants Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.	Total n=489 Participants Total of all reporting groups
Age, Continuous	46.7 years STANDARD_DEVIATION 14.83 • n=5 Participants	46.6 years STANDARD_DEVIATION 13.82 • n=7 Participants	46.6 years STANDARD_DEVIATION 14.32 • n=5 Participants
Sex: Female, Male Female	161 Participants n=5 Participants	142 Participants n=7 Participants	303 Participants n=5 Participants
Sex: Female, Male Male	83 Participants n=5 Participants	103 Participants n=7 Participants	186 Participants n=5 Participants
Race/Ethnicity, Customized White	182 participants n=5 Participants	173 participants n=7 Participants	355 participants n=5 Participants
Race/Ethnicity, Customized Black	20 participants n=5 Participants	14 participants n=7 Participants	34 participants n=5 Participants
Race/Ethnicity, Customized Asian	33 participants n=5 Participants	50 participants n=7 Participants	83 participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaskan Native	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Race/Ethnicity, Customized Pacific Islander	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Other	9 participants n=5 Participants	7 participants n=7 Participants	16 participants n=5 Participants
Race/Ethnicity, Customized Non-Hispanic and non-Latino	223 participants n=5 Participants	216 participants n=7 Participants	439 participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	21 participants n=5 Participants	28 participants n=7 Participants	49 participants n=5 Participants
Race/Ethnicity, Customized Unknown	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Weight	76.5 kg STANDARD_DEVIATION 18.71 • n=5 Participants	75.6 kg STANDARD_DEVIATION 19.05 • n=7 Participants	76.0 kg STANDARD_DEVIATION 18.87 • n=5 Participants
Height	165.0 cm STANDARD_DEVIATION 9.74 • n=5 Participants	164.9 cm STANDARD_DEVIATION 10.42 • n=7 Participants	164.9 cm STANDARD_DEVIATION 10.07 • n=5 Participants
Body Mass Index	28.0 kg/m^2 STANDARD_DEVIATION 6.16 • n=5 Participants	27.7 kg/m^2 STANDARD_DEVIATION 6.26 • n=7 Participants	27.9 kg/m^2 STANDARD_DEVIATION 6.20 • n=5 Participants
Oral Glucocorticosteroid (OCS) Use at Baseline OCS - Yes	46 participants n=5 Participants	46 participants n=7 Participants	92 participants n=5 Participants
Oral Glucocorticosteroid (OCS) Use at Baseline OCS - No	198 participants n=5 Participants	199 participants n=7 Participants	397 participants n=5 Participants
Asthma Exacerbations In Previous 12 Months	2.1 exacerbations STANDARD_DEVIATION 2.31 • n=5 Participants	1.9 exacerbations STANDARD_DEVIATION 1.63 • n=7 Participants	2.0 exacerbations STANDARD_DEVIATION 2.00 • n=5 Participants
Forced Expiratory Volume in 1 Second	1.928 liters STANDARD_DEVIATION 0.7908 • n=5 Participants	1.894 liters STANDARD_DEVIATION 0.7258 • n=7 Participants	1.911 liters STANDARD_DEVIATION 0.7583 • n=5 Participants
Asthma Control Questionnaire (ACQ) Overall Score	2.763 units on a scale STANDARD_DEVIATION 0.8782 • n=5 Participants	2.657 units on a scale STANDARD_DEVIATION 0.8541 • n=7 Participants	2.710 units on a scale STANDARD_DEVIATION 0.867 • n=5 Participants
Asthma Quality of Life Questionnaire (AQLQ)	4.159 units on a scale STANDARD_DEVIATION 1.0883 • n=5 Participants	4.303 units on a scale STANDARD_DEVIATION 1.1208 • n=7 Participants	4.231 units on a scale STANDARD_DEVIATION 1.1059 • n=5 Participants
Asthma Symptom Utility Index (ASUI)	0.613 units on a scale STANDARD_DEVIATION 0.2029 • n=5 Participants	0.633 units on a scale STANDARD_DEVIATION 0.1938 • n=7 Participants	0.623 units on a scale STANDARD_DEVIATION 0.1984 • n=5 Participants
Number of Short-Acting Beta-Agonist Puffs (SABA) Daily	2.7 puffs/day STANDARD_DEVIATION 3.18 • n=5 Participants	2.4 puffs/day STANDARD_DEVIATION 2.82 • n=7 Participants	2.6 puffs/day STANDARD_DEVIATION 3.01 • n=5 Participants

PRIMARY outcome

Timeframe: Day 1 to Week 52

Population: Randomized set

Outcome measures

Outcome measures
Measure	Placebo n=244 Participants Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.	Reslizumab 3.0 mg/kg n=245 Participants Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.
Frequency of Clinical Asthma Exacerbations (CAEs) During 12 Months of Treatment	1.804 CAEs in 52 weeks Interval 1.372 to 2.372	0.904 CAEs in 52 weeks Interval 0.678 to 1.205

PRIMARY outcome

Timeframe: Day 1 to Week 52

Population: Randomized set

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.

Outcome measures

Outcome measures
Measure	Placebo n=244 Participants Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.	Reslizumab 3.0 mg/kg n=245 Participants Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.
Frequency of Each of the Two Criteria for Clinical Asthma Exacerbations (CAEs) Requiring systemic corticosterioids >3 days	1.604 CAEs in 52 weeks Interval 1.195 to 2.152	0.722 CAEs in 52 weeks Interval 0.528 to 0.986
Frequency of Each of the Two Criteria for Clinical Asthma Exacerbations (CAEs) Requiring hospitalization or ER visit	0.207 CAEs in 52 weeks Interval 0.107 to 0.4	0.137 CAEs in 52 weeks Interval 0.068 to 0.274

SECONDARY outcome

Timeframe: Day 1 (baseline, pre-dose), Weeks 4, 8, 12 and 16

Population: Randomized set, including participants who contributed at least once to the analysis.

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.

Outcome measures

Outcome measures
Measure	Placebo n=241 Participants Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.	Reslizumab 3.0 mg/kg n=243 Participants Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Over 16 Weeks Using Mixed Model for Repeated Measures	0.110 liters Standard Error 0.031	0.248 liters Standard Error 0.030

SECONDARY outcome

Timeframe: Day 1 (baseline, pre-dose), Week 16

Population: Randomized set of patients with assessments at both timepoints

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.

Outcome measures

Outcome measures
Measure	Placebo n=229 Participants Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.	Reslizumab 3.0 mg/kg n=228 Participants Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) to Week 16	0.695 units on a scale Standard Error 0.088	0.933 units on a scale Standard Error 0.088

SECONDARY outcome

Timeframe: Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16

Population: Randomized set, including participants who contributed at least once to the analysis.

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.

Outcome measures

Outcome measures
Measure	Placebo n=241 Participants Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.	Reslizumab 3.0 mg/kg n=242 Participants Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.
Change From Baseline in Asthma Control Questionnaire (ACQ) Over 16 Weeks Using Mixed Model for Repeated Measures	-0.676 units on a scale Standard Error 0.066	-0.941 units on a scale Standard Error 0.065

SECONDARY outcome

Timeframe: Day 1 to Day 478 (longest treatment time plus 2 weeks)

Population: Randomized set

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).

Outcome measures

Outcome measures
Measure	Placebo n=244 Participants Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.	Reslizumab 3.0 mg/kg n=245 Participants Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.
Kaplan-Meier Estimates for Time to First Clinical Asthma Exacerbation (CAE)	34.9 weeks Interval 23.3 to Insufficient data to estimate time	NA weeks Insufficient data to estimate time

SECONDARY outcome

Timeframe: Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16

Population: Randomized set, including participants who contributed at least once to the analysis.

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.

Outcome measures

Outcome measures
Measure	Placebo n=238 Participants Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.	Reslizumab 3.0 mg/kg n=238 Participants Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.
Change From Baseline in Asthma Symptom Utility Index (ASUI) Over 16 Weeks Using Mixed Model for Repeated Measures	0.109 units on a scale Standard Error 0.012	0.167 units on a scale Standard Error 0.188

SECONDARY outcome

Timeframe: Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16

Population: Randomized set of participants with assessments within the timeframe

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.

Outcome measures

Outcome measures
Measure	Placebo n=238 Participants Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.	Reslizumab 3.0 mg/kg n=240 Participants Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.
Change From Baseline in Short-Acting Beta-Agonist (SABA) Use Over 16 Weeks Using Mixed Model for Repeated Measures	-0.36 puffs/day Standard Error 0.158	-0.64 puffs/day Standard Error 0.156

SECONDARY outcome

Timeframe: Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 or early withdrawal

Population: Randomized set of participants with assessments within timeframe

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.

Outcome measures

Outcome measures
Measure	Placebo n=241 Participants Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.	Reslizumab 3.0 mg/kg n=243 Participants Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.
Change From Baseline in Blood Eosinophil Count Over 16 Weeks and 52 Weeks Using Mixed Model for Repeated Measures Over first 16 weeks	-0.118 10^9 blood eosinophil/L Standard Error 0.0232	-0.584 10^9 blood eosinophil/L Standard Error 0.0230
Change From Baseline in Blood Eosinophil Count Over 16 Weeks and 52 Weeks Using Mixed Model for Repeated Measures Over 52 weeks	-0.127 10^9 blood eosinophil/L Standard Error 0.0168	-0.582 10^9 blood eosinophil/L Standard Error 0.0167

SECONDARY outcome

Timeframe: Day 1 (post-dose) to Week 65. The last postbaseline value for approximately 20 patients in each

Population: Safety analysis set

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.

Outcome measures

Outcome measures
Measure	Placebo n=243 Participants Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.	Reslizumab 3.0 mg/kg n=245 Participants Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.
Participants With Treatment-Emergent Adverse Events At least 1 AE	206 participants	197 participants
Participants With Treatment-Emergent Adverse Events Mild severity AE	41 participants	68 participants
Participants With Treatment-Emergent Adverse Events Moderate severity AE	133 participants	107 participants
Participants With Treatment-Emergent Adverse Events Severe AE	32 participants	22 participants
Participants With Treatment-Emergent Adverse Events Treatment-related AE	36 participants	36 participants
Participants With Treatment-Emergent Adverse Events Treatment-related mild AE	23 participants	24 participants
Participants With Treatment-Emergent Adverse Events Treatment-related moderate AE	13 participants	9 participants
Participants With Treatment-Emergent Adverse Events Treatment-related severe AE	0 participants	3 participants
Participants With Treatment-Emergent Adverse Events AE causing patient discontinuation	8 participants	4 participants
Participants With Treatment-Emergent Adverse Events Serious AE	34 participants	24 participants
Participants With Treatment-Emergent Adverse Events Deaths	1 participants	0 participants

SECONDARY outcome

Timeframe: Week 4 to Week 65. The last postbaseline value for approximately 20 patients in each

Population: Safety analysis set

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

Outcome measures

Outcome measures
Measure	Placebo n=243 Participants Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.	Reslizumab 3.0 mg/kg n=245 Participants Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Blood urea nitrogen	9 participants	8 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Uric acid	9 participants	6 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Aspartate aminotransferase	1 participants	1 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Alanine aminotransferase	3 participants	5 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Gamma-glutamyl transpeptidase	12 participants	12 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Bilirubin	2 participants	1 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values White blood cells - low	6 participants	6 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values White blood cells - high	5 participants	3 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Hemoglobin	7 participants	4 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Hematocrit	9 participants	6 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Neutrophils	8 participants	6 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Eosinophils	135 participants	3 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Platelets - low	1 participants	2 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Platelets - high	2 participants	0 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Urinalysis - Blood (hemoglobin)	32 participants	21 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Urinalysis - Ketones	4 participants	5 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Urinalysis - Glucose	11 participants	14 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Urinalysis - Protein	32 participants	34 participants

SECONDARY outcome

Timeframe: Week 4 to Week 65. The last postbaseline value for approximately 20 patients in each

Population: Safety analysis set

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

Outcome measures

Outcome measures
Measure	Placebo n=243 Participants Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.	Reslizumab 3.0 mg/kg n=245 Participants Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values Sitting pulse - high 12-17 yr	1 participants	1 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values Sitting pulse - low >=18 yr	1 participants	0 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values Sitting pulse - high >=18 yr	5 participants	7 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values Sitting systolic blood pressure - low >=18 yr	2 participants	5 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values Sitting diastolic blood pressure - low 12-17 yr	1 participants	0 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values Sitting diastolic blood pressure - low >=18 yr	0 participants	1 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values Sitting diastolic blood pressure - high >=18 yr	10 participants	5 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values Respiratory rate >=18 yr	3 participants	2 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values Body temperature - low 12-17 yr	1 participants	1 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values Body temperature - low >=18 yr	54 participants	49 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values Body temperature - high >=18 yr	0 participants	1 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values Sitting systolic blood pressure - high >=18 yr	7 participants	7 participants

SECONDARY outcome

Timeframe: Weeks 16, 32, 48 and 52

Population: Safety analysis set. Immunogenicity for anti-reslizumab antibodies not reported for the placebo treatment arm.

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.

Outcome measures

Outcome measures
Measure	Placebo Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.	Reslizumab 3.0 mg/kg n=245 Participants Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.
Participants With a Positive Anti-Reslizumab Antibody Status During Study	—	8 participants

Adverse Events

Placebo

Serious events: 34 serious events

Other events: 184 other events

Deaths: 0 deaths

Reslizumab 3.0 mg/kg

Serious events: 24 serious events

Other events: 165 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=243 participants at risk Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.	Reslizumab 3.0 mg/kg n=245 participants at risk Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.
Cardiac disorders Right ventricular failure	0.41% 1/243 • Number of events 1 • Day 1 to Day 464	0.00% 0/245 • Day 1 to Day 464
Cardiac disorders Sinus tachycardia	0.41% 1/243 • Number of events 1 • Day 1 to Day 464	0.00% 0/245 • Day 1 to Day 464
Gastrointestinal disorders Diaphragmatic hernia	0.00% 0/243 • Day 1 to Day 464	0.41% 1/245 • Number of events 1 • Day 1 to Day 464
Gastrointestinal disorders Diarrhoea	0.41% 1/243 • Number of events 1 • Day 1 to Day 464	0.00% 0/245 • Day 1 to Day 464
Gastrointestinal disorders Oesophagitis	0.00% 0/243 • Day 1 to Day 464	0.41% 1/245 • Number of events 1 • Day 1 to Day 464
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/243 • Day 1 to Day 464	0.41% 1/245 • Number of events 1 • Day 1 to Day 464
General disorders Chest pain	0.00% 0/243 • Day 1 to Day 464	0.82% 2/245 • Number of events 2 • Day 1 to Day 464
Infections and infestations Bronchitis	0.82% 2/243 • Number of events 3 • Day 1 to Day 464	0.00% 0/245 • Day 1 to Day 464
Infections and infestations Diverticulitis	0.41% 1/243 • Number of events 1 • Day 1 to Day 464	0.00% 0/245 • Day 1 to Day 464
Infections and infestations Gastroenteritis	0.41% 1/243 • Number of events 1 • Day 1 to Day 464	0.41% 1/245 • Number of events 1 • Day 1 to Day 464
Infections and infestations Influenza	0.00% 0/243 • Day 1 to Day 464	0.41% 1/245 • Number of events 1 • Day 1 to Day 464
Infections and infestations Lower respiratory tract infection	0.41% 1/243 • Number of events 1 • Day 1 to Day 464	0.00% 0/245 • Day 1 to Day 464
Infections and infestations Otitis media	0.41% 1/243 • Number of events 1 • Day 1 to Day 464	0.00% 0/245 • Day 1 to Day 464
Infections and infestations Periorbital cellulitis	0.41% 1/243 • Number of events 1 • Day 1 to Day 464	0.00% 0/245 • Day 1 to Day 464
Infections and infestations Pneumonia	0.00% 0/243 • Day 1 to Day 464	0.82% 2/245 • Number of events 2 • Day 1 to Day 464
Infections and infestations Sinusitis	0.41% 1/243 • Number of events 1 • Day 1 to Day 464	0.00% 0/245 • Day 1 to Day 464
Infections and infestations Urinary tract infection	0.41% 1/243 • Number of events 1 • Day 1 to Day 464	0.00% 0/245 • Day 1 to Day 464
Infections and infestations Viral infection	0.41% 1/243 • Number of events 1 • Day 1 to Day 464	0.00% 0/245 • Day 1 to Day 464
Injury, poisoning and procedural complications Concussion	0.00% 0/243 • Day 1 to Day 464	0.41% 1/245 • Number of events 1 • Day 1 to Day 464
Injury, poisoning and procedural complications Face injury	0.00% 0/243 • Day 1 to Day 464	0.41% 1/245 • Number of events 1 • Day 1 to Day 464
Injury, poisoning and procedural complications Procedural nausea	0.00% 0/243 • Day 1 to Day 464	0.41% 1/245 • Number of events 1 • Day 1 to Day 464
Injury, poisoning and procedural complications Procedural vomiting	0.00% 0/243 • Day 1 to Day 464	0.41% 1/245 • Number of events 1 • Day 1 to Day 464
Injury, poisoning and procedural complications Radius fracture	0.00% 0/243 • Day 1 to Day 464	0.41% 1/245 • Number of events 1 • Day 1 to Day 464
Injury, poisoning and procedural complications Rib fracture	0.41% 1/243 • Number of events 1 • Day 1 to Day 464	0.00% 0/245 • Day 1 to Day 464
Injury, poisoning and procedural complications Thermal burn	0.41% 1/243 • Number of events 1 • Day 1 to Day 464	0.00% 0/245 • Day 1 to Day 464
Injury, poisoning and procedural complications Tibia fracture	0.41% 1/243 • Number of events 1 • Day 1 to Day 464	0.00% 0/245 • Day 1 to Day 464
Injury, poisoning and procedural complications Toxicity to various agents	0.41% 1/243 • Number of events 1 • Day 1 to Day 464	0.00% 0/245 • Day 1 to Day 464
Injury, poisoning and procedural complications Ulna fracture	0.00% 0/243 • Day 1 to Day 464	0.41% 1/245 • Number of events 1 • Day 1 to Day 464
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.00% 0/243 • Day 1 to Day 464	0.41% 1/245 • Number of events 1 • Day 1 to Day 464
Musculoskeletal and connective tissue disorders Osteonecrosis	0.41% 1/243 • Number of events 1 • Day 1 to Day 464	0.00% 0/245 • Day 1 to Day 464
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder transitional cell carcinoma	0.41% 1/243 • Number of events 1 • Day 1 to Day 464	0.00% 0/245 • Day 1 to Day 464
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.41% 1/243 • Number of events 1 • Day 1 to Day 464	0.00% 0/245 • Day 1 to Day 464
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	0.00% 0/243 • Day 1 to Day 464	0.41% 1/245 • Number of events 1 • Day 1 to Day 464
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.00% 0/243 • Day 1 to Day 464	0.41% 1/245 • Number of events 1 • Day 1 to Day 464
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to liver	0.41% 1/243 • Number of events 1 • Day 1 to Day 464	0.00% 0/245 • Day 1 to Day 464
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to lung	0.41% 1/243 • Number of events 1 • Day 1 to Day 464	0.00% 0/245 • Day 1 to Day 464
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.00% 0/243 • Day 1 to Day 464	0.41% 1/245 • Number of events 1 • Day 1 to Day 464
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.00% 0/243 • Day 1 to Day 464	0.41% 1/245 • Number of events 1 • Day 1 to Day 464
Nervous system disorders Meningism	0.41% 1/243 • Number of events 1 • Day 1 to Day 464	0.00% 0/245 • Day 1 to Day 464
Nervous system disorders Nerve compression	0.41% 1/243 • Number of events 1 • Day 1 to Day 464	0.00% 0/245 • Day 1 to Day 464
Nervous system disorders Neurological symptom	0.41% 1/243 • Number of events 1 • Day 1 to Day 464	0.00% 0/245 • Day 1 to Day 464
Nervous system disorders Status migrainosus	0.41% 1/243 • Number of events 2 • Day 1 to Day 464	0.00% 0/245 • Day 1 to Day 464
Renal and urinary disorders Ureteric obstruction	0.41% 1/243 • Number of events 1 • Day 1 to Day 464	0.00% 0/245 • Day 1 to Day 464
Respiratory, thoracic and mediastinal disorders Asthma	5.3% 13/243 • Number of events 28 • Day 1 to Day 464	4.5% 11/245 • Number of events 12 • Day 1 to Day 464
Respiratory, thoracic and mediastinal disorders Nasal polyps	0.41% 1/243 • Number of events 1 • Day 1 to Day 464	0.00% 0/245 • Day 1 to Day 464
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.41% 1/243 • Number of events 1 • Day 1 to Day 464	0.00% 0/245 • Day 1 to Day 464
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	0.41% 1/243 • Number of events 1 • Day 1 to Day 464	0.00% 0/245 • Day 1 to Day 464
Vascular disorders Deep vein thrombosis	0.00% 0/243 • Day 1 to Day 464	0.41% 1/245 • Number of events 1 • Day 1 to Day 464

Other adverse events

Other adverse events
Measure	Placebo n=243 participants at risk Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.	Reslizumab 3.0 mg/kg n=245 participants at risk Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.
Infections and infestations Bronchitis	9.1% 22/243 • Number of events 31 • Day 1 to Day 464	5.3% 13/245 • Number of events 14 • Day 1 to Day 464
Infections and infestations Influenza	9.5% 23/243 • Number of events 32 • Day 1 to Day 464	6.9% 17/245 • Number of events 25 • Day 1 to Day 464
Infections and infestations Nasopharyngitis	13.6% 33/243 • Number of events 44 • Day 1 to Day 464	11.4% 28/245 • Number of events 45 • Day 1 to Day 464
Infections and infestations Pharyngitis	5.3% 13/243 • Number of events 13 • Day 1 to Day 464	4.1% 10/245 • Number of events 11 • Day 1 to Day 464
Infections and infestations Sinusitis	11.5% 28/243 • Number of events 48 • Day 1 to Day 464	8.6% 21/245 • Number of events 31 • Day 1 to Day 464
Infections and infestations Upper respiratory tract infection	13.2% 32/243 • Number of events 49 • Day 1 to Day 464	15.9% 39/245 • Number of events 50 • Day 1 to Day 464
Infections and infestations Urinary tract infection	4.1% 10/243 • Number of events 13 • Day 1 to Day 464	5.3% 13/245 • Number of events 15 • Day 1 to Day 464
Musculoskeletal and connective tissue disorders Back pain	5.3% 13/243 • Number of events 13 • Day 1 to Day 464	5.3% 13/245 • Number of events 15 • Day 1 to Day 464
Nervous system disorders Dizziness	5.3% 13/243 • Number of events 13 • Day 1 to Day 464	2.0% 5/245 • Number of events 7 • Day 1 to Day 464
Nervous system disorders Headache	12.3% 30/243 • Number of events 50 • Day 1 to Day 464	7.8% 19/245 • Number of events 31 • Day 1 to Day 464
Respiratory, thoracic and mediastinal disorders Asthma	50.6% 123/243 • Number of events 364 • Day 1 to Day 464	37.6% 92/245 • Number of events 192 • Day 1 to Day 464
Respiratory, thoracic and mediastinal disorders Cough	5.3% 13/243 • Number of events 14 • Day 1 to Day 464	4.5% 11/245 • Number of events 13 • Day 1 to Day 464
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	3.3% 8/243 • Number of events 9 • Day 1 to Day 464	5.3% 13/245 • Number of events 17 • Day 1 to Day 464
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	2.5% 6/243 • Number of events 7 • Day 1 to Day 464	5.3% 13/245 • Number of events 16 • Day 1 to Day 464

Additional Information

Director, Clinical Research

Teva Branded Pharmaceutical Products, R&D Inc

Phone: 215-591-3000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
Publication restrictions are in place

Restriction type: OTHER