Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of Reslizumab (0.3 or 3.0 mg/kg) as Treatment for Patients (12-75 Years of Age) With Eosinophilic Asthma (NCT NCT01270464)

Last Updated: 2016-06-06

Results Overview

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. 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. Positive change from baseline scores indicate improvement in asthma control.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

315 participants

Primary outcome timeframe

Day 0 (baseline, pre-dose), Weeks 4, 8, 12 and 16

Results posted on

2016-06-06

Participant Flow

Of the 1025 patients screened at 80 centers in 12 countries (Argentina, Belgium, Brazil, Canada, Colombia, Hungary, Israel, Mexico, Netherlands, Poland, Sweden, and the US), 315 patients met entry criteria at 68 centers and were considered to be eligible for enrollment.

Participant milestones

Participant milestones
Measure	Placebo Placebo administered intravenously (iv) once every 4 weeks, for a total of 4 doses.	Reslizumab - 0.3 mg/kg 0.3 mg/kg, administered intravenously (iv) once every 4 weeks, for a total of 4 doses	Reslizumab - 3.0 mg/kg 3.0 mg/kg, administered intravenously (iv) once every 4 weeks, for a total of 4 doses.
Overall Study STARTED	105	104	106
Overall Study Safety Analysis Set	105	103	103
Overall Study Full Analysis Set	105	103	103
Overall Study Pharmacokinetic Analysis Set	105	103	103
Overall Study COMPLETED	85	92	88
Overall Study NOT COMPLETED	20	12	18

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo administered intravenously (iv) once every 4 weeks, for a total of 4 doses.	Reslizumab - 0.3 mg/kg 0.3 mg/kg, administered intravenously (iv) once every 4 weeks, for a total of 4 doses	Reslizumab - 3.0 mg/kg 3.0 mg/kg, administered intravenously (iv) once every 4 weeks, for a total of 4 doses.
Overall Study Protocol Violation	4	3	2
Overall Study Lack of Efficacy	2	3	1
Overall Study Adverse Event	9	1	7
Overall Study Withdrawal by Subject	2	1	4
Overall Study Lost to Follow-up	2	3	1
Overall Study Other	1	1	3

Baseline Characteristics

A Study to Evaluate the Efficacy and Safety of Reslizumab (0.3 or 3.0 mg/kg) as Treatment for Patients (12-75 Years of Age) With Eosinophilic Asthma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=105 Participants Placebo administered intravenously (iv) once every 4 weeks, for a total of 4 doses.	Reslizumab - 0.3 mg/kg n=104 Participants 0.3 mg/kg, administered intravenously (iv) once every 4 weeks, for a total of 4 doses	Reslizumab - 3.0 mg/kg n=106 Participants 3.0 mg/kg, administered intravenously (iv) once every 4 weeks, for a total of 4 doses.	Total n=315 Participants Total of all reporting groups
Age, Continuous	44.2 years STANDARD_DEVIATION 14.89 • n=5 Participants	44.5 years STANDARD_DEVIATION 14.03 • n=7 Participants	43.0 years STANDARD_DEVIATION 14.41 • n=5 Participants	43.9 years STANDARD_DEVIATION 14.42 • n=4 Participants
Age, Customized Adolescents (12-17 years)	5 participants n=5 Participants	5 participants n=7 Participants	5 participants n=5 Participants	15 participants n=4 Participants
Age, Customized Adults (18-64 years)	93 participants n=5 Participants	91 participants n=7 Participants	99 participants n=5 Participants	283 participants n=4 Participants
Age, Customized From 65-84 years	7 participants n=5 Participants	8 participants n=7 Participants	2 participants n=5 Participants	17 participants n=4 Participants
Sex: Female, Male Female	62 Participants n=5 Participants	59 Participants n=7 Participants	62 Participants n=5 Participants	183 Participants n=4 Participants
Sex: Female, Male Male	43 Participants n=5 Participants	45 Participants n=7 Participants	44 Participants n=5 Participants	132 Participants n=4 Participants
Race/Ethnicity, Customized White	85 participants n=5 Participants	80 participants n=7 Participants	90 participants n=5 Participants	255 participants n=4 Participants
Race/Ethnicity, Customized Black	7 participants n=5 Participants	6 participants n=7 Participants	5 participants n=5 Participants	18 participants n=4 Participants
Race/Ethnicity, Customized Asian	0 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants	4 participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaskan Native	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Race/Ethnicity, Customized Pacific Islander	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Race/Ethnicity, Customized Other	11 participants n=5 Participants	16 participants n=7 Participants	9 participants n=5 Participants	36 participants n=4 Participants
Race/Ethnicity, Customized Hispanic or Latino	29 participants n=5 Participants	29 participants n=7 Participants	31 participants n=5 Participants	89 participants n=4 Participants
Race/Ethnicity, Customized Non-Hispanic and Non-Latino	74 participants n=5 Participants	73 participants n=7 Participants	75 participants n=5 Participants	222 participants n=4 Participants
Race/Ethnicity, Customized Unknown	2 participants n=5 Participants	2 participants n=7 Participants	0 participants n=5 Participants	4 participants n=4 Participants
Asthma Exacerbation Within the Last 12 Months Yes	57 participants n=5 Participants	58 participants n=7 Participants	60 participants n=5 Participants	175 participants n=4 Participants
Asthma Exacerbation Within the Last 12 Months No	48 participants n=5 Participants	46 participants n=7 Participants	46 participants n=5 Participants	140 participants n=4 Participants
Weight	77.0 kg STANDARD_DEVIATION 20.1 • n=5 Participants	75.9 kg STANDARD_DEVIATION 18.8 • n=7 Participants	75.7 kg STANDARD_DEVIATION 20.3 • n=5 Participants	76.2 kg STANDARD_DEVIATION 19.70 • n=4 Participants
Height	166.4 cm STANDARD_DEVIATION 10.93 • n=5 Participants	166.2 cm STANDARD_DEVIATION 12.21 • n=7 Participants	165.9 cm STANDARD_DEVIATION 10.24 • n=5 Participants	166.2 cm STANDARD_DEVIATION 11.12 • n=4 Participants
Body Mass Index	27.7 kg/m^2 STANDARD_DEVIATION 6.01 • n=5 Participants	27.6 kg/m^2 STANDARD_DEVIATION 6.68 • n=7 Participants	27.4 kg/m^2 STANDARD_DEVIATION 6.87 • n=5 Participants	27.6 kg/m^2 STANDARD_DEVIATION 6.51 • n=4 Participants

PRIMARY outcome

Timeframe: Day 0 (baseline, pre-dose), Weeks 4, 8, 12 and 16

Population: Full analysis set-all patients randomly assigned to treatment and treated with at least 1 dose of study drug. Number of participants analyzed includes those who contributed at least once to the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=103 Participants Placebo administered intravenously (iv) once every 4 weeks, for a total of 4 doses.	Reslizumab - 0.3 mg/kg n=101 Participants 0.3 mg/kg, administered intravenously (iv) once every 4 weeks, for a total of 4 doses	Reslizumab - 3.0 mg/kg n=102 Participants 3.0 mg/kg, administered intravenously (iv) once every 4 weeks, for a total of 4 doses.
Change From Baseline In Forced Expiratory Volume In 1 Second (FEV1) Over 16 Weeks Using Mixed Model for Repeated Measures	0.126 liters Standard Error 0.0549	0.242 liters Standard Error 0.0556	0.286 liters Standard Error 0.0548

SECONDARY outcome

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

Population: Full analysis set. Number of participants analyzed includes those who contributed at least once to the analysis.

The FVC is the volume of air that can be forcibly blown out after full inspiration, measured in liters. The during treatment (weeks 4, 8, 12 and 16) average FVC 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=103 Participants Placebo administered intravenously (iv) once every 4 weeks, for a total of 4 doses.	Reslizumab - 0.3 mg/kg n=101 Participants 0.3 mg/kg, administered intravenously (iv) once every 4 weeks, for a total of 4 doses	Reslizumab - 3.0 mg/kg n=102 Participants 3.0 mg/kg, administered intravenously (iv) once every 4 weeks, for a total of 4 doses.
Change From Baseline in Forced Vital Capacity (FVC) Over 16 Weeks Using Mixed Model for Repeated Measures	0.172 liters Standard Error 0.0614	0.220 liters Standard Error 0.0623	0.301 liters Standard Error 0.0613

SECONDARY outcome

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

Population: Full analysis set. Number of participants analyzed includes those who contributed at least once to the analysis.

The FEF 25%-75% is the force expiratory flow at 25% to 75% of the Forced Vital Capacity (FVC). The during treatment (weeks 4, 8, 12 and 16) average FEF 25%-75% 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=103 Participants Placebo administered intravenously (iv) once every 4 weeks, for a total of 4 doses.	Reslizumab - 0.3 mg/kg n=101 Participants 0.3 mg/kg, administered intravenously (iv) once every 4 weeks, for a total of 4 doses	Reslizumab - 3.0 mg/kg n=102 Participants 3.0 mg/kg, administered intravenously (iv) once every 4 weeks, for a total of 4 doses.
Change From Baseline in Forced Expiratory Flow at 25% to 75% Forced Vital Capacity (FEF 25%-75%) Over 16 Weeks Using Mixed Model for Repeated Measures	-0.145 liters/second Standard Error 0.1342	-0.114 liters/second Standard Error 0.1361	0.089 liters/second Standard Error 0.1342

SECONDARY outcome

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

Population: Full analysis set of participants with assessments at stated timeframes.

The percent predicted FEV1 is the ratio of the volume of air expired in the first second of a forced expiration to the patient's predicted FEV based on a similar population without asthma. Endpoint =week 16 or early withdrawal.

Outcome measures

Outcome measures
Measure	Placebo n=103 Participants Placebo administered intravenously (iv) once every 4 weeks, for a total of 4 doses.	Reslizumab - 0.3 mg/kg n=101 Participants 0.3 mg/kg, administered intravenously (iv) once every 4 weeks, for a total of 4 doses	Reslizumab - 3.0 mg/kg n=102 Participants 3.0 mg/kg, administered intravenously (iv) once every 4 weeks, for a total of 4 doses.
Change From Baseline in % Predicted Expiratory Volume In 1 Second (FEV1) at Week 16 and at Endpoint Week 16 (n=84, 92, 91)	0.8 percentage of predicted FEV1 Standard Deviation 11.92	4.9 percentage of predicted FEV1 Standard Deviation 15.06	7.5 percentage of predicted FEV1 Standard Deviation 14.74
Change From Baseline in % Predicted Expiratory Volume In 1 Second (FEV1) at Week 16 and at Endpoint Endpoint (n=103, 101, 102)	0.8 percentage of predicted FEV1 Standard Deviation 13.83	5.5 percentage of predicted FEV1 Standard Deviation 15.16	6.7 percentage of predicted FEV1 Standard Deviation 15.01

SECONDARY outcome

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

Population: Full analysis 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=103 Participants Placebo administered intravenously (iv) once every 4 weeks, for a total of 4 doses.	Reslizumab - 0.3 mg/kg n=101 Participants 0.3 mg/kg, administered intravenously (iv) once every 4 weeks, for a total of 4 doses	Reslizumab - 3.0 mg/kg n=101 Participants 3.0 mg/kg, administered intravenously (iv) once every 4 weeks, for a total of 4 doses.
Change From Baseline in Asthma Control Questionnaire (ACQ) Over 16 Weeks Using Mixed Model for Repeated Measures	-0.494 units on a scale Standard Error 0.1231	-0.732 units on a scale Standard Error 0.1250	-0.853 units on a scale Standard Error 0.1233

SECONDARY outcome

Timeframe: Day 1 (baseline, pre-dose), Week 16 or last observed value

Population: Full analysis set of participants with assessments at stated timeframes.

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. The AQLQ score was only assessed once during the study at week 16 or at early withdrawal, i.e. last postbaseline assessment if within 3 to 5 weeks of the last dose of study drug.

Outcome measures

Outcome measures
Measure	Placebo n=101 Participants Placebo administered intravenously (iv) once every 4 weeks, for a total of 4 doses.	Reslizumab - 0.3 mg/kg n=96 Participants 0.3 mg/kg, administered intravenously (iv) once every 4 weeks, for a total of 4 doses	Reslizumab - 3.0 mg/kg n=99 Participants 3.0 mg/kg, administered intravenously (iv) once every 4 weeks, for a total of 4 doses.
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) at Week 16 or at Last Observed Value	0.779 units on a scale Standard Error 0.1817	1.057 units on a scale Standard Error 0.1881	1.138 units on a scale Standard Error 0.1829

SECONDARY outcome

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

Population: Full analysis set, including patients 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. 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=103 Participants Placebo administered intravenously (iv) once every 4 weeks, for a total of 4 doses.	Reslizumab - 0.3 mg/kg n=101 Participants 0.3 mg/kg, administered intravenously (iv) once every 4 weeks, for a total of 4 doses	Reslizumab - 3.0 mg/kg n=101 Participants 3.0 mg/kg, administered intravenously (iv) once every 4 weeks, for a total of 4 doses.
Change From Baseline in Asthma Symptom Utility Index (ASUI) Over 16 Weeks Using Mixed Model for Repeated Measures	0.082 units on a scale Standard Error 0.0218	0.132 units on a scale Standard Error 0.0221	0.129 units on a scale Standard Error 0.0218

SECONDARY outcome

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

Population: Full analysis set, including patients who contributed at least once to the analysis.

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) average 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=102 Participants Placebo administered intravenously (iv) once every 4 weeks, for a total of 4 doses.	Reslizumab - 0.3 mg/kg n=101 Participants 0.3 mg/kg, administered intravenously (iv) once every 4 weeks, for a total of 4 doses	Reslizumab - 3.0 mg/kg n=102 Participants 3.0 mg/kg, administered intravenously (iv) once every 4 weeks, for a total of 4 doses.
Change From Baseline in Short-Acting Beta-Agonist (SABA) Use Over 16 Weeks Using Mixed Model for Repeated Measures	-0.3 SABA puffs per day Standard Error 0.28	-1.0 SABA puffs per day Standard Error 0.28	-0.9 SABA puffs per day Standard Error 0.27

SECONDARY outcome

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

Population: Full analysis set, including patients who contributed at least once to the analysis.

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 (weeks 4, 8, 12 and 16) 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=103 Participants Placebo administered intravenously (iv) once every 4 weeks, for a total of 4 doses.	Reslizumab - 0.3 mg/kg n=101 Participants 0.3 mg/kg, administered intravenously (iv) once every 4 weeks, for a total of 4 doses	Reslizumab - 3.0 mg/kg n=102 Participants 3.0 mg/kg, administered intravenously (iv) once every 4 weeks, for a total of 4 doses.
Change From Baseline in Blood Eosinophil Count Over 16 Weeks Using Mixed Model for Repeated Measures	-0.035 10^9 blood eosinophil/L Standard Error 0.0271	-0.358 10^9 blood eosinophil/L Standard Error 0.0277	-0.529 10^9 blood eosinophil/L Standard Error 0.0270

SECONDARY outcome

Timeframe: Day 1 (post-dose) to Week 29

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. The last postbaseline value for approximately 10 patients in each treatment group is the 90-day follow-up visit post end-of-treatment (approx. Week 29).

Outcome measures

Outcome measures
Measure	Placebo n=105 Participants Placebo administered intravenously (iv) once every 4 weeks, for a total of 4 doses.	Reslizumab - 0.3 mg/kg n=103 Participants 0.3 mg/kg, administered intravenously (iv) once every 4 weeks, for a total of 4 doses	Reslizumab - 3.0 mg/kg n=103 Participants 3.0 mg/kg, administered intravenously (iv) once every 4 weeks, for a total of 4 doses.
Participants With Adverse Events At least 1 AE	66 participants	59 participants	61 participants
Participants With Adverse Events Severe AE	4 participants	2 participants	7 participants
Participants With Adverse Events Treatment-related AE	8 participants	6 participants	12 participants
Participants With Adverse Events Withdrawn from study due to AE	10 participants	1 participants	6 participants
Participants With Adverse Events Withdrawn due to treatment-related AE	0 participants	0 participants	1 participants
Participants With Adverse Events Death	0 participants	0 participants	0 participants
Participants With Adverse Events Serious AE (excluding death outcome)	1 participants	0 participants	4 participants
Participants With Adverse Events Treatment-related serious AEs	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Day 2 to Week 29

Population: Safety analysis set

Data represents participants with potentially clinically significant (PCS) abnormal serum chemistry, hematology (except for eosinophil values), and urinalysis values. Significance criteria: * Blood urea nitrogen: \>=10.71 mmol/L * Creatinine: \>=177 μmol/L * Uric acid: M\>=625, F\>=506 μmol/L * GGT = gamma-glutamyl transpeptidase: \>= 3\*upper limit of normal. Normal range is 5-49 U/L. * Total bilirubin: \>=34.2 μmol/L * White blood cells: \<=3.0 10\^9/L * Hemoglobin: M\<=115, F\<=95 g/dL * Hematocrit: M\<0.37, F\<0.32 % * Platelets: \>=700 10\^9/L * Absolute neutrophil count: \<=1.0 10\^9/L * Urinalysis: blood, glucose, ketones and total protein: \>=2 unit increase from baseline The last postbaseline value for approximately 10 patients in each treatment group is the 90-day follow-up visit post end-of-treatment (approx. Week 29).

Outcome measures

Outcome measures
Measure	Placebo n=105 Participants Placebo administered intravenously (iv) once every 4 weeks, for a total of 4 doses.	Reslizumab - 0.3 mg/kg n=103 Participants 0.3 mg/kg, administered intravenously (iv) once every 4 weeks, for a total of 4 doses	Reslizumab - 3.0 mg/kg n=103 Participants 3.0 mg/kg, administered intravenously (iv) once every 4 weeks, for a total of 4 doses.
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Creatinine	1 participants	0 participants	0 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Uric acid	0 participants	0 participants	2 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values GGT	0 participants	4 participants	0 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Total bilirubin	0 participants	1 participants	0 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values >=1 PCS abnormal hematology value	4 participants	7 participants	3 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values White blood cells	0 participants	0 participants	1 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Hemoglobin	0 participants	2 participants	0 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Hematocrit	2 participants	6 participants	2 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Platelets	0 participants	0 participants	1 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Absolute neutrophil count	2 participants	1 participants	0 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values >=1 PCS abnormal urinalysis value	21 participants	21 participants	18 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Blood in urine	10 participants	11 participants	6 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Glucose in urine	3 participants	4 participants	5 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Ketones in urine	0 participants	1 participants	3 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Total protein in urine	11 participants	11 participants	11 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values >=1 PCS abnormal serum chemistry value	1 participants	5 participants	2 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Blood urea nitrogen	0 participants	0 participants	1 participants

SECONDARY outcome

Timeframe: Day 2 to Week 29

Population: Safety analysis set

Data represents participants with potentially clinically significant (PCS) vital sign values. Significance criteria * Sitting pulse - high: \>100 and increase of \>= 30 beats/minute * Sitting pulse - low: \<50 and decrease of \>=30 beats/minute * Sitting diastolic blood pressure: \>100 and increase of \>=12 mmHg * Respiration rate: \>24 and increase of \>=10 breaths/minute * Body temperature: \<96.5° Fahrenheit or \<35.8° Celsius The last postbaseline value for approximately 10 patients in each treatment group is the 90-day follow-up visit post end-of-treatment (approx. Week 29).

Outcome measures

Outcome measures
Measure	Placebo n=105 Participants Placebo administered intravenously (iv) once every 4 weeks, for a total of 4 doses.	Reslizumab - 0.3 mg/kg n=103 Participants 0.3 mg/kg, administered intravenously (iv) once every 4 weeks, for a total of 4 doses	Reslizumab - 3.0 mg/kg n=103 Participants 3.0 mg/kg, administered intravenously (iv) once every 4 weeks, for a total of 4 doses.
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values >=1 PCS abnormal vital sign	12 participants	16 participants	16 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values Sitting pulse - high	0 participants	1 participants	2 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values Sitting pulse - low	0 participants	1 participants	1 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values Sitting diastolic blood pressure - high	0 participants	0 participants	1 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values Respiration rate - high	0 participants	2 participants	0 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values Body temperature - low	12 participants	13 participants	13 participants

SECONDARY outcome

Timeframe: Weeks -4 to -2 (Screening Visit), Week 16

Population: Safety analysis set of participants with both baseline and endpoint values.

Participant counts in each category of shift from baseline to endpoint of ECG finding. Findings summarized as normal or abnormal.

Outcome measures

Outcome measures
Measure	Placebo n=102 Participants Placebo administered intravenously (iv) once every 4 weeks, for a total of 4 doses.	Reslizumab - 0.3 mg/kg n=99 Participants 0.3 mg/kg, administered intravenously (iv) once every 4 weeks, for a total of 4 doses	Reslizumab - 3.0 mg/kg n=101 Participants 3.0 mg/kg, administered intravenously (iv) once every 4 weeks, for a total of 4 doses.
Shifts From Baseline to Endpoint in Electrocardiogram Findings Normal to Normal	64 participants	70 participants	63 participants
Shifts From Baseline to Endpoint in Electrocardiogram Findings Normal to Abnormal	14 participants	10 participants	15 participants
Shifts From Baseline to Endpoint in Electrocardiogram Findings Abnormal to Normal	11 participants	9 participants	13 participants
Shifts From Baseline to Endpoint in Electrocardiogram Findings Abnormal to Abnormal	13 participants	10 participants	10 participants

SECONDARY outcome

Timeframe: Day 1 (pre-dose), week 8, 16 and endpoint

Population: Pharmacokinetic analysis set. Anti-Reslizumab antibody status was not analyzed for patients in the Placebo treatment arm.

Counts of participants with a positive anti-drug antibody (ADA) response during treatment is offered for the two experimental treatment arms. Blood samples were collected for determination of ADAs before study drug infusion at baseline, visit 4 (week 8), and at visit 6 (week 16: EOT or early withdrawal) from patients in all 3 treatment groups (ie, placebo, 0.3 mg/kg reslizumab, and 3.0 mg/kg reslizumab); however, only the blood samples drawn from patients treated with either 0.3 mg/kg reslizumab or 3.0 mg/kg reslizumab were analyzed. Serum samples from patients who were treated with reslizumab were analyzed for ADA by Teva (Teva Biopharmaceuticals USA, Rockville, MD) using a validated homogeneous solution-based bridging enzyme-linked immunosorbent assay (ELISA). Endpoint =week 16 or early withdrawal.

Outcome measures

Outcome measures
Measure	Placebo Placebo administered intravenously (iv) once every 4 weeks, for a total of 4 doses.	Reslizumab - 0.3 mg/kg n=103 Participants 0.3 mg/kg, administered intravenously (iv) once every 4 weeks, for a total of 4 doses	Reslizumab - 3.0 mg/kg n=103 Participants 3.0 mg/kg, administered intravenously (iv) once every 4 weeks, for a total of 4 doses.
Participants With a Positive Anti-Reslizumab Antibody Status at Baseline, Week 8, Week 16, Endpoint, and Overall Overall (n=102, 103)	—	12 participants	11 participants
Participants With a Positive Anti-Reslizumab Antibody Status at Baseline, Week 8, Week 16, Endpoint, and Overall Baseline (n=99, 98)	—	8 participants	8 participants
Participants With a Positive Anti-Reslizumab Antibody Status at Baseline, Week 8, Week 16, Endpoint, and Overall Week 8 (n=90, 94)	—	8 participants	10 participants
Participants With a Positive Anti-Reslizumab Antibody Status at Baseline, Week 8, Week 16, Endpoint, and Overall Week 16 (n=91, 89)	—	7 participants	5 participants
Participants With a Positive Anti-Reslizumab Antibody Status at Baseline, Week 8, Week 16, Endpoint, and Overall Endpoint (n=101, 102)	—	10 participants	6 participants

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 28 other events

Deaths: 0 deaths

Reslizumab - 0.3 mg/kg

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

Reslizumab - 3.0 mg/kg

Serious events: 4 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=105 participants at risk Placebo administered intravenously (iv) once every 4 weeks, for a total of 4 doses.	Reslizumab - 0.3 mg/kg n=103 participants at risk 0.3 mg/kg, administered intravenously (iv) once every 4 weeks, for a total of 4 doses	Reslizumab - 3.0 mg/kg n=103 participants at risk 3.0 mg/kg, administered intravenously (iv) once every 4 weeks, for a total of 4 doses.
Cardiac disorders Acute myocardial infarction	0.95% 1/105 • Number of events 1 • Day 1 to Week 29. The last postbaseline value for approximately 10 patients in each treatment group is the 90-day follow-up visit post end-of-treatment (approx. Week 29). Events reported during the followup were treated as treatment-emergent.	0.00% 0/103 • Day 1 to Week 29. The last postbaseline value for approximately 10 patients in each treatment group is the 90-day follow-up visit post end-of-treatment (approx. Week 29). Events reported during the followup were treated as treatment-emergent.	0.00% 0/103 • Day 1 to Week 29. The last postbaseline value for approximately 10 patients in each treatment group is the 90-day follow-up visit post end-of-treatment (approx. Week 29). Events reported during the followup were treated as treatment-emergent.
Infections and infestations Pneumonia	0.00% 0/105 • Day 1 to Week 29. The last postbaseline value for approximately 10 patients in each treatment group is the 90-day follow-up visit post end-of-treatment (approx. Week 29). Events reported during the followup were treated as treatment-emergent.	0.00% 0/103 • Day 1 to Week 29. The last postbaseline value for approximately 10 patients in each treatment group is the 90-day follow-up visit post end-of-treatment (approx. Week 29). Events reported during the followup were treated as treatment-emergent.	0.97% 1/103 • Number of events 1 • Day 1 to Week 29. The last postbaseline value for approximately 10 patients in each treatment group is the 90-day follow-up visit post end-of-treatment (approx. Week 29). Events reported during the followup were treated as treatment-emergent.
Infections and infestations Sinusitis	0.00% 0/105 • Day 1 to Week 29. The last postbaseline value for approximately 10 patients in each treatment group is the 90-day follow-up visit post end-of-treatment (approx. Week 29). Events reported during the followup were treated as treatment-emergent.	0.00% 0/103 • Day 1 to Week 29. The last postbaseline value for approximately 10 patients in each treatment group is the 90-day follow-up visit post end-of-treatment (approx. Week 29). Events reported during the followup were treated as treatment-emergent.	0.97% 1/103 • Number of events 1 • Day 1 to Week 29. The last postbaseline value for approximately 10 patients in each treatment group is the 90-day follow-up visit post end-of-treatment (approx. Week 29). Events reported during the followup were treated as treatment-emergent.
Injury, poisoning and procedural complications Rib fracture	0.00% 0/105 • Day 1 to Week 29. The last postbaseline value for approximately 10 patients in each treatment group is the 90-day follow-up visit post end-of-treatment (approx. Week 29). Events reported during the followup were treated as treatment-emergent.	0.00% 0/103 • Day 1 to Week 29. The last postbaseline value for approximately 10 patients in each treatment group is the 90-day follow-up visit post end-of-treatment (approx. Week 29). Events reported during the followup were treated as treatment-emergent.	0.97% 1/103 • Number of events 1 • Day 1 to Week 29. The last postbaseline value for approximately 10 patients in each treatment group is the 90-day follow-up visit post end-of-treatment (approx. Week 29). Events reported during the followup were treated as treatment-emergent.
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/105 • Day 1 to Week 29. The last postbaseline value for approximately 10 patients in each treatment group is the 90-day follow-up visit post end-of-treatment (approx. Week 29). Events reported during the followup were treated as treatment-emergent.	0.00% 0/103 • Day 1 to Week 29. The last postbaseline value for approximately 10 patients in each treatment group is the 90-day follow-up visit post end-of-treatment (approx. Week 29). Events reported during the followup were treated as treatment-emergent.	0.97% 1/103 • Number of events 1 • Day 1 to Week 29. The last postbaseline value for approximately 10 patients in each treatment group is the 90-day follow-up visit post end-of-treatment (approx. Week 29). Events reported during the followup were treated as treatment-emergent.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/105 • Day 1 to Week 29. The last postbaseline value for approximately 10 patients in each treatment group is the 90-day follow-up visit post end-of-treatment (approx. Week 29). Events reported during the followup were treated as treatment-emergent.	0.00% 0/103 • Day 1 to Week 29. The last postbaseline value for approximately 10 patients in each treatment group is the 90-day follow-up visit post end-of-treatment (approx. Week 29). Events reported during the followup were treated as treatment-emergent.	2.9% 3/103 • Number of events 3 • Day 1 to Week 29. The last postbaseline value for approximately 10 patients in each treatment group is the 90-day follow-up visit post end-of-treatment (approx. Week 29). Events reported during the followup were treated as treatment-emergent.

Other adverse events

Other adverse events
Measure	Placebo n=105 participants at risk Placebo administered intravenously (iv) once every 4 weeks, for a total of 4 doses.	Reslizumab - 0.3 mg/kg n=103 participants at risk 0.3 mg/kg, administered intravenously (iv) once every 4 weeks, for a total of 4 doses	Reslizumab - 3.0 mg/kg n=103 participants at risk 3.0 mg/kg, administered intravenously (iv) once every 4 weeks, for a total of 4 doses.
Infections and infestations Nasopharyngitis	3.8% 4/105 • Number of events 5 • Day 1 to Week 29. The last postbaseline value for approximately 10 patients in each treatment group is the 90-day follow-up visit post end-of-treatment (approx. Week 29). Events reported during the followup were treated as treatment-emergent.	5.8% 6/103 • Number of events 9 • Day 1 to Week 29. The last postbaseline value for approximately 10 patients in each treatment group is the 90-day follow-up visit post end-of-treatment (approx. Week 29). Events reported during the followup were treated as treatment-emergent.	5.8% 6/103 • Number of events 6 • Day 1 to Week 29. The last postbaseline value for approximately 10 patients in each treatment group is the 90-day follow-up visit post end-of-treatment (approx. Week 29). Events reported during the followup were treated as treatment-emergent.
Nervous system disorders Headache	5.7% 6/105 • Number of events 7 • Day 1 to Week 29. The last postbaseline value for approximately 10 patients in each treatment group is the 90-day follow-up visit post end-of-treatment (approx. Week 29). Events reported during the followup were treated as treatment-emergent.	7.8% 8/103 • Number of events 9 • Day 1 to Week 29. The last postbaseline value for approximately 10 patients in each treatment group is the 90-day follow-up visit post end-of-treatment (approx. Week 29). Events reported during the followup were treated as treatment-emergent.	10.7% 11/103 • Number of events 11 • Day 1 to Week 29. The last postbaseline value for approximately 10 patients in each treatment group is the 90-day follow-up visit post end-of-treatment (approx. Week 29). Events reported during the followup were treated as treatment-emergent.
Respiratory, thoracic and mediastinal disorders Asthma	19.0% 20/105 • Number of events 24 • Day 1 to Week 29. The last postbaseline value for approximately 10 patients in each treatment group is the 90-day follow-up visit post end-of-treatment (approx. Week 29). Events reported during the followup were treated as treatment-emergent.	5.8% 6/103 • Number of events 10 • Day 1 to Week 29. The last postbaseline value for approximately 10 patients in each treatment group is the 90-day follow-up visit post end-of-treatment (approx. Week 29). Events reported during the followup were treated as treatment-emergent.	13.6% 14/103 • Number of events 14 • Day 1 to Week 29. The last postbaseline value for approximately 10 patients in each treatment group is the 90-day follow-up visit post end-of-treatment (approx. Week 29). Events reported during the followup were treated as treatment-emergent.

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.
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Restriction type: OTHER