Trial Outcomes & Findings for Study to Evaluate the Efficacy and Safety of Reslizumab Treatment in Patients With Moderate to Severe Asthma (NCT NCT01508936)

NCT ID: NCT01508936

Last Updated: 2016-06-27

Results Overview

FEV1 is a standard measurement of air movement in the lungs of patients with asthma. It is the volume of air expired in the first second of a forced expiration. Improvement in FEV1 is a measure in the reduction of bronchospasm, the reduction of airway inflammation, or both. FEV1 was measured using forced expiratory air spirometry. Data represent the slope estimate of change from baseline in FEV1 (measured in liters) at Week 16 versus baseline eosinophil count (measured in 10\^9/liter) by treatment group.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 511 participants
• Primary outcome timeframe: Baseline (Day 1), Week 16
• Results posted on: 2016-06-27

Participant Flow

A total of 869 patients were screened for enrollment into this study. Of the 869 patients screened, 511 patients at 103 centers in the US met entry criteria and were considered to be eligible for enrollment into the study.

Randomization was stratified by occurrence of asthma exacerbation(s) during the previous year (yes or no). Within each stratum, patients were randomly assigned in a 4:1 ratio to receive treatment with reslizumab at 3.0 mg/kg or matching placebo.

Participant milestones

Measure	Placebo Placebo intravenous injection every 4 weeks for a total of 4 doses.	Reslizumab 3.0 mg/kg Reslizumab intravenous injection at a dosage of 3.0 mg/kg every 4 weeks for a total of 4 doses.
Overall Study STARTED	102	409
Overall Study Randomized, Not Analyzed	4	11
Overall Study Randomized	98	398
Overall Study Randomized, Not Treated	1	3
Overall Study Safety Analysis Set	97	395
Overall Study Full Analysis Set	97	395
Overall Study FEV1 Subpopulation Analysis Set	91	346
Overall Study COMPLETED	79	330
Overall Study NOT COMPLETED	23	79

Reasons for withdrawal

Measure	Placebo Placebo intravenous injection every 4 weeks for a total of 4 doses.	Reslizumab 3.0 mg/kg Reslizumab intravenous injection at a dosage of 3.0 mg/kg every 4 weeks for a total of 4 doses.
Overall Study Adverse Event	11	32
Overall Study Lack of Efficacy	0	1
Overall Study Withdrawal by Subject	4	18
Overall Study Protocol Violation	2	3
Overall Study Lost to Follow-up	2	9
Overall Study Other	0	5
Overall Study Data from 2 sites deemed invalid	4	11

Baseline Characteristics

Study to Evaluate the Efficacy and Safety of Reslizumab Treatment in Patients With Moderate to Severe Asthma

Baseline characteristics by cohort

Measure	Placebo n=98 Participants Placebo intravenous injection every 4 weeks for a total of 4 doses.	Reslizumab 3.0 mg/kg n=398 Participants Reslizumab intravenous injection at a dosage of 3.0 mg/kg every 4 weeks for a total of 4 doses.	Total n=496 Participants Total of all reporting groups
Age, Continuous	45.1 years STANDARD_DEVIATION 13.38 • n=5 Participants	44.9 years STANDARD_DEVIATION 12.00 • n=7 Participants	44.9 years STANDARD_DEVIATION 12.27 • n=5 Participants
Sex: Female, Male Female	54 Participants n=5 Participants	261 Participants n=7 Participants	315 Participants n=5 Participants
Sex: Female, Male Male	44 Participants n=5 Participants	137 Participants n=7 Participants	181 Participants n=5 Participants
Race/Ethnicity, Customized White	73 participants n=5 Participants	260 participants n=7 Participants	333 participants n=5 Participants
Race/Ethnicity, Customized Black	21 participants n=5 Participants	113 participants n=7 Participants	134 participants n=5 Participants
Race/Ethnicity, Customized Asian	2 participants n=5 Participants	10 participants n=7 Participants	12 participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaskan Native	0 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants
Race/Ethnicity, Customized Pacific Islander	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants
Race/Ethnicity, Customized Other	0 participants n=5 Participants	12 participants n=7 Participants	12 participants n=5 Participants
Race/Ethnicity, Customized Non-Hispanic and Non-Latino	90 participants n=5 Participants	354 participants n=7 Participants	444 participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	8 participants n=5 Participants	44 participants n=7 Participants	52 participants n=5 Participants
Weight	90.9 kg STANDARD_DEVIATION 20.68 • n=5 Participants	90.6 kg STANDARD_DEVIATION 23.92 • n=7 Participants	90.7 kg STANDARD_DEVIATION 23.30 • n=5 Participants
Height	169.7 cm STANDARD_DEVIATION 10.25 • n=5 Participants	167.7 cm STANDARD_DEVIATION 10.35 • n=7 Participants	168.1 cm STANDARD_DEVIATION 10.35 • n=5 Participants
Body Mass Index	31.6 kg/m^2 STANDARD_DEVIATION 6.66 • n=5 Participants	32.2 kg/m^2 STANDARD_DEVIATION 8.69 • n=7 Participants	32.2 kg/m^2 STANDARD_DEVIATION 8.33 • n=5 Participants
Asthma Control Questionnaire (ACQ)	2.564 units on a scale STANDARD_DEVIATION 0.6909 • n=5 Participants	2.558 units on a scale STANDARD_DEVIATION 0.6992 • n=7 Participants	2.559 units on a scale STANDARD_DEVIATION 0.6969 • n=5 Participants
Forced Expiratory Volume in 1 second (FEV1)	2.180 liters STANDARD_DEVIATION 0.6355 • n=5 Participants	2.101 liters STANDARD_DEVIATION 0.6950 • n=7 Participants	2.117 liters STANDARD_DEVIATION 0.6837 • n=5 Participants
Forced Vital Capacity (FVC)	3.215 liters STANDARD_DEVIATION 0.9076 • n=5 Participants	3.047 liters STANDARD_DEVIATION 0.9577 • n=7 Participants	3.081 liters STANDARD_DEVIATION 0.9494 • n=5 Participants
Forced Expiratory Flow at 25% to 75% of the Forced Vital Capacity (FEF25%-75%)	1.553 liters/second STANDARD_DEVIATION 0.6791 • n=5 Participants	1.650 liters/second STANDARD_DEVIATION 0.9037 • n=7 Participants	1.631 liters/second STANDARD_DEVIATION 0.8645 • n=5 Participants
Percent Predicted Forced Expiratory Volume in 1 Second (% predicted FEV1)	66.5 % predicted STANDARD_DEVIATION 15.53 • n=5 Participants	66.8 % predicted STANDARD_DEVIATION 16.26 • n=7 Participants	66.7 % predicted STANDARD_DEVIATION 16.10 • n=5 Participants
Blood Eosinophil Counts	0.277 10^9 blood eosinophil/liter STANDARD_DEVIATION 0.2209 • n=5 Participants	0.281 10^9 blood eosinophil/liter STANDARD_DEVIATION 0.2448 • n=7 Participants	0.280 10^9 blood eosinophil/liter STANDARD_DEVIATION 0.2401 • n=5 Participants
Average Daily Use of Short-Acting Beta-Agonist Therapy (SABA) in Past 3 Days	2.0 puffs of SABA/day STANDARD_DEVIATION 1.82 • n=5 Participants	1.9 puffs of SABA/day STANDARD_DEVIATION 1.84 • n=7 Participants	1.9 puffs of SABA/day STANDARD_DEVIATION 1.83 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1), Week 16

Population: Full analysis set (FAS) includes randomized patients treated with at least 1 dose of study drug, and had assessments in the timeframes. Pulmonary function tests were excluded if a limited subset of medications that could significantly confound interpretation were used within 7 days of scheduled visits.

FEV1 is a standard measurement of air movement in the lungs of patients with asthma. It is the volume of air expired in the first second of a forced expiration. Improvement in FEV1 is a measure in the reduction of bronchospasm, the reduction of airway inflammation, or both. FEV1 was measured using forced expiratory air spirometry.

Data represent the slope estimate of change from baseline in FEV1 (measured in liters) at Week 16 versus baseline eosinophil count (measured in 10^9/liter) by treatment group.

Outcome measures

Measure	Placebo n=83 Participants Placebo intravenous injection every 4 weeks for a total of 4 doses.	Reslizumab 3.0 mg/kg n=344 Participants Reslizumab intravenous injection at a dosage of 3.0 mg/kg every 4 weeks for a total of 4 doses.
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 16 in Full Analysis Set	-0.2778 FEV1 liters/ eosinophils 10^9/liter Standard Error 0.2379	0.0229 FEV1 liters/ eosinophils 10^9/liter Standard Error 0.0944

SECONDARY outcome

Timeframe: Baseline (Day 1), Weeks 4, 8, 12, 16

Population: Full analysis set (FAS) includes randomized patients treated with at least 1 dose of study drug, and contributed at least once to the analysis. Pulmonary function tests were excluded if a limited subset of medications that could significantly confound interpretation were used within 7 days of scheduled visits.

FEV1 is a standard measurement of air movement in the lungs of patients with asthma. It is the volume of air expired in the first second of a forced expiration. Improvement in FEV1 is a measure in the reduction of bronchospasm, the reduction of airway inflammation, or both. FEV1 was measured using forced expiratory air spirometry. Positive change from baseline scores indicate improvement in asthma control.

During study (Weeks 4, 8, 12 and 16) average value was calculated using a mixed effects model for repeated measures (MMRM) with treatment (reslizumab or placebo), blood eosinophil count at baseline, and the interaction of treatment and eosinophil count as a random effect.

Outcome measures

Measure	Placebo n=96 Participants Placebo intravenous injection every 4 weeks for a total of 4 doses.	Reslizumab 3.0 mg/kg n=390 Participants Reslizumab intravenous injection at a dosage of 3.0 mg/kg 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	0.175 liters Standard Error 0.0377	0.251 liters Standard Error 0.0200

SECONDARY outcome

Timeframe: Baseline (Day 1), Weeks 4, 8, 12, 16

Population: Full analysis set of participants who contributed at least once to the analysis. ACQ were excluded from the FAS if they were obtained at scheduled visits which were preceded by usage within 7 days of a limited subset of medications that could significantly confound interpretation.

The ACQ score was measured using the ACQ-7. Six questions are-self assessments; the seventh item is the result of the patient's % predicted 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 score of 0 indicates good asthma control; higher scores indicate increasingly poorer asthma control. Negative change from baseline scores indicate improvement in asthma control.

During study (Weeks 4, 8, 12 and 16) average value was calculated from mixed model repeated measures (MMRM) with treatment, visit, treatment by visit interaction, history of asthma exacerbation in the previous year, height, baseline value, and sex as fixed factors, and patient as a random effect.

Outcome measures

Measure	Placebo n=96 Participants Placebo intravenous injection every 4 weeks for a total of 4 doses.	Reslizumab 3.0 mg/kg n=390 Participants Reslizumab intravenous injection at a dosage of 3.0 mg/kg 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	-0.614 units on a scale Standard Error 0.0689	-0.737 units on a scale Standard Error 0.0364

SECONDARY outcome

Timeframe: Baseline (Day 1), Week 16

Population: The FEV1 sub-population analysis set includes all participants in the FAS with % predicted FEV1 \<85% at baseline. Pulmonary function tests were excluded if a limited subset of medications that could significantly confound interpretation were used within 7 days of scheduled visits.

FEV1 is a standard measurement of air movement in the lungs of patients with asthma. It is the volume of air expired in the first second of a forced expiration. Improvement in FEV1 is a measure in the reduction of bronchospasm, the reduction of airway inflammation, or both. FEV1 was measured using forced expiratory air spirometry.

As with the primary outcome, data represent the slope estimate of change from baseline in FEV1 (measured in liters) at Week 16 versus baseline eosinophil count (measured in 10^9/liter) by treatment group. However the FEV1 subpopulation includes participants with more impaired lung function (% predicted FEV1 <85% at baseline).

Outcome measures

Measure	Placebo n=91 Participants Placebo intravenous injection every 4 weeks for a total of 4 doses.	Reslizumab 3.0 mg/kg n=346 Participants Reslizumab intravenous injection at a dosage of 3.0 mg/kg every 4 weeks for a total of 4 doses.
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 16 in FEV1 Subpopulation	-0.2944 FEV1 liters/ eosinophils 10^9/liter Standard Error 0.2443	0.0271 FEV1 liters/ eosinophils 10^9/liter Standard Error 0.1019

SECONDARY outcome

Timeframe: Baseline (Day 1), Weeks 4, 8, 12, and 16

Population: Full analysis set. Number of participants analyzed represents # with FEV1 baseline values (one reslizumab participant was missing a valid baseline FEV1.) Number participants with assessments in the timeframes are listed with the time designation.

FEV1 is a standard measurement of air movement in the lungs of patients with asthma. It is the volume of air expired in the first second of a forced expiration. Improvement in FEV1 is a measure in the reduction of bronchospasm, the reduction of airway inflammation, or both. FEV1 was measured using forced expiratory air spirometry. Positive change from baseline scores indicate improvement in asthma control.

Outcome measures

Measure	Placebo n=97 Participants Placebo intravenous injection every 4 weeks for a total of 4 doses.	Reslizumab 3.0 mg/kg n=394 Participants Reslizumab intravenous injection at a dosage of 3.0 mg/kg every 4 weeks for a total of 4 doses.
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Weeks 4, 8, 12, and 16 Week 4 (n= 96, 386)	0.164 liters Standard Error 0.0395	0.224 liters Standard Error 0.0208
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Weeks 4, 8, 12, and 16 Week 8 (n= 93, 377)	0.199 liters Standard Error 0.0421	0.249 liters Standard Error 0.0220
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Weeks 4, 8, 12, and 16 Week 12 (n= 90, 357)	0.152 liters Standard Error 0.0430	0.277 liters Standard Error 0.0226
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Weeks 4, 8, 12, and 16 Week 16 (n=83, 344)	0.187 liters Standard Error 0.0446	0.255 liters Standard Error 0.0232

SECONDARY outcome

Timeframe: Baseline (Day 1), Weeks 4, 8, 12, and 16

Population: Full analysis set. Number of participants analyzed represents # with FEV1 baseline values (one reslizumab participant was missing a valid baseline FEV1.) Number participants with assessments in the timeframes are listed with the time designation.

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. Percent predicted lung function values were transcribed directly from the lung function report to the CRF, without any calculation by Teva. Positive change from baseline scores indicate improvement in asthma control.

Outcome measures

Measure	Placebo n=97 Participants Placebo intravenous injection every 4 weeks for a total of 4 doses.	Reslizumab 3.0 mg/kg n=394 Participants Reslizumab intravenous injection at a dosage of 3.0 mg/kg every 4 weeks for a total of 4 doses.
Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (% Predicted FEV1) at Weeks 4, 8, 12, 16 and Endpoint Week 4 (n=96, 385)	4.8 percentage of predicted FEV1 Standard Deviation 9.83	6.7 percentage of predicted FEV1 Standard Deviation 12.26
Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (% Predicted FEV1) at Weeks 4, 8, 12, 16 and Endpoint Week 8 (n=93, 377)	6.0 percentage of predicted FEV1 Standard Deviation 9.9	7.2 percentage of predicted FEV1 Standard Deviation 13.41
Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (% Predicted FEV1) at Weeks 4, 8, 12, 16 and Endpoint Week 12 (n=90, 357)	4.2 percentage of predicted FEV1 Standard Deviation 10.36	8.2 percentage of predicted FEV1 Standard Deviation 13.23
Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (% Predicted FEV1) at Weeks 4, 8, 12, 16 and Endpoint Week 16 (n=83, 344)	5.5 percentage of predicted FEV1 Standard Deviation 11.76	7.8 percentage of predicted FEV1 Standard Deviation 13.60
Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (% Predicted FEV1) at Weeks 4, 8, 12, 16 and Endpoint Endpoint (n=96, 390)	5.2 percentage of predicted FEV1 Standard Deviation 11.76	7.5 percentage of predicted FEV1 Standard Deviation 13.26

SECONDARY outcome

Timeframe: Baseline (Day 1), Weeks 4, 8, 12, and 16

Population: Full analysis set. Number of participants analyzed represents # with FVC baseline values (one reslizumab participant was missing a valid baseline FVC.) Number participants with assessments in the timeframes are listed with the time designation.

The FVC is the volume of air that can be forcibly blown out after full inspiration, measured in liters. FV was measured using forced expiratory air spirometry. Positive change from baseline scores indicate improvement in asthma control.

Outcome measures

Measure	Placebo n=97 Participants Placebo intravenous injection every 4 weeks for a total of 4 doses.	Reslizumab 3.0 mg/kg n=394 Participants Reslizumab intravenous injection at a dosage of 3.0 mg/kg every 4 weeks for a total of 4 doses.
Change From Baseline in Forced Vital Capacity (FVC) at Weeks 4, 8, 12, and 16 Week 4 (n=96, 386)	0.167 liters Standard Error 0.0469	0.235 liters Standard Error 0.0247
Change From Baseline in Forced Vital Capacity (FVC) at Weeks 4, 8, 12, and 16 Week 8 (n=93, 377)	0.179 liters Standard Error 0.0474	0.243 liters Standard Error 0.0249
Change From Baseline in Forced Vital Capacity (FVC) at Weeks 4, 8, 12, and 16 Week 12 (n=90, 357)	0.176 liters Standard Error 0.0500	0.284 liters Standard Error 0.0263
Change From Baseline in Forced Vital Capacity (FVC) at Weeks 4, 8, 12, and 16 Week 16 (n=84, 345)	0.234 liters Standard Error 0.0506	0.246 liters Standard Error 0.0264

SECONDARY outcome

Timeframe: Baseline (Day 1), Weeks 4, 8, 12, and 16

Population: Full analysis set. Number of participants analyzed represents # with FEF25%-75% baseline values. Number of participants with assessments in the timeframes are listed with the time designation.

The FEF25%-75% is the forced expiratory flow at 25% to 75% of the forced vital capacity. FEF25%-75% was measured using forced expiratory air spirometry. Positive change from baseline scores indicate improvement in asthma control.

Outcome measures

Measure	Placebo n=95 Participants Placebo intravenous injection every 4 weeks for a total of 4 doses.	Reslizumab 3.0 mg/kg n=391 Participants Reslizumab intravenous injection at a dosage of 3.0 mg/kg every 4 weeks for a total of 4 doses.
Change From Baseline in the Forced Expiratory Flow at 25% to 75% of the Forced Vital Capacity (FEF25%-75%) at Weeks 4, 8, 12, and 16 Week 4 (n=93, 382)	0.210 liters/second Standard Error 0.0565	0.184 liters/second Standard Error 0.0295
Change From Baseline in the Forced Expiratory Flow at 25% to 75% of the Forced Vital Capacity (FEF25%-75%) at Weeks 4, 8, 12, and 16 Week 8 (n=90, 374)	0.270 liters/second Standard Error 0.0609	0.240 liters/second Standard Error 0.0315
Change From Baseline in the Forced Expiratory Flow at 25% to 75% of the Forced Vital Capacity (FEF25%-75%) at Weeks 4, 8, 12, and 16 Week 12 (n=87, 354)	0.136 liters/second Standard Error 0.0635	0.256 liters/second Standard Error 0.0329
Change From Baseline in the Forced Expiratory Flow at 25% to 75% of the Forced Vital Capacity (FEF25%-75%) at Weeks 4, 8, 12, and 16 Week 16 (n=82, 342)	0.179 liters/second Standard Error 0.0875	0.241 liters/second Standard Error 0.0441

SECONDARY outcome

Timeframe: Baseline (Day -2 to 1), Weeks 4, 8, 12, and 16

Population: Full analysis set. Number of participants analyzed represents # with SABA use baseline values. Number participants with assessments in the timeframes are listed with the time designation.

SABA are used for quick relief of asthma symptoms. The number of times SABA therapy was used was assessed using 3 day recall at scheduled visits. Participants were asked to recall whether SABAs were used within 3 days of the scheduled visit and, if so, how many puffs were used. Daily use was the average of those 3 days. Negative change from baseline scores indicate improvement in asthma control.

Outcome measures

Measure	Placebo n=96 Participants Placebo intravenous injection every 4 weeks for a total of 4 doses.	Reslizumab 3.0 mg/kg n=392 Participants Reslizumab intravenous injection at a dosage of 3.0 mg/kg every 4 weeks for a total of 4 doses.
Change From Baseline in Average Daily Use of Short-Acting Beta-Agonist Therapy (SABA) at Weeks 4, 8, 12, and 16 Week 4 (n=96, 388)	-0.1 puffs of SABA/day Standard Error 0.19	-0.2 puffs of SABA/day Standard Error 0.10
Change From Baseline in Average Daily Use of Short-Acting Beta-Agonist Therapy (SABA) at Weeks 4, 8, 12, and 16 Week 8 (n=94, 377)	-0.2 puffs of SABA/day Standard Error 0.18	-0.3 puffs of SABA/day Standard Error 0.09
Change From Baseline in Average Daily Use of Short-Acting Beta-Agonist Therapy (SABA) at Weeks 4, 8, 12, and 16 Week 12 (n=89, 356)	-0.2 puffs of SABA/day Standard Error 0.20	-0.3 puffs of SABA/day Standard Error 0.10
Change From Baseline in Average Daily Use of Short-Acting Beta-Agonist Therapy (SABA) at Weeks 4, 8, 12, and 16 Week 16 (n=84, 345)	-0.4 puffs of SABA/day Standard Error 0.18	-0.3 puffs of SABA/day Standard Error 0.09

SECONDARY outcome

Timeframe: Baseline (Day 1), Weeks 4, 8, 12, 16, Follow-up (Week 28)

Population: Full analysis set. Number of participants analyzed represents # with blood eosinophil count baseline values. Number participants with assessments in the timeframes are listed with the time designation.

Blood eosinophil counts were measured using a standard complete blood count with differential blood test at each scheduled visit. Follow-up was performed approximately 12 weeks after the 16 week treatment period. Endpoint is the last post-baseline assessment.

Outcome measures

Measure	Placebo n=95 Participants Placebo intravenous injection every 4 weeks for a total of 4 doses.	Reslizumab 3.0 mg/kg n=394 Participants Reslizumab intravenous injection at a dosage of 3.0 mg/kg every 4 weeks for a total of 4 doses.
Change From Baseline in Blood Eosinophil Counts at Weeks 4, 8, 12, 16, Follow-up (Week 28) and Endpoint Week 4 (n=93, 385)	0.010 10^9/liter Standard Deviation 0.1917	-0.226 10^9/liter Standard Deviation 0.2297
Change From Baseline in Blood Eosinophil Counts at Weeks 4, 8, 12, 16, Follow-up (Week 28) and Endpoint Week 8 (n=91, 372)	0.036 10^9/liter Standard Deviation 0.3104	-0.239 10^9/liter Standard Deviation 0.2389
Change From Baseline in Blood Eosinophil Counts at Weeks 4, 8, 12, 16, Follow-up (Week 28) and Endpoint Week 12 (n=84, 353)	0.027 10^9/liter Standard Deviation 0.2082	-0.240 10^9/liter Standard Deviation 0.2418
Change From Baseline in Blood Eosinophil Counts at Weeks 4, 8, 12, 16, Follow-up (Week 28) and Endpoint Week 16 (n=80, 346)	0.021 10^9/liter Standard Deviation 02466	-0.239 10^9/liter Standard Deviation 0.2462
Change From Baseline in Blood Eosinophil Counts at Weeks 4, 8, 12, 16, Follow-up (Week 28) and Endpoint Follow-up (n=90, 364)	0.035 10^9/liter Standard Deviation 0.3369	-0.159 10^9/liter Standard Deviation 0.2301
Change From Baseline in Blood Eosinophil Counts at Weeks 4, 8, 12, 16, Follow-up (Week 28) and Endpoint Endpoint (n=94, 392)	0.036 10^9/liter Standard Deviation 0.3306	-0.169 10^9/liter Standard Deviation 0.2294

SECONDARY outcome

Timeframe: Baseline (Day 1), Weeks 4, 8, 12 and 16

Population: Full analysis set. Number of participants analyzed represents # with ACQ baseline values. Number participants with assessments in the timeframes are listed with the time designation. ACQ were excluded if obtained at visits which were preceded by usage within 7 days of a limited subset of medications that could significantly alter interpretation.

The ACQ score was measured using the ACQ-7. Six questions are self-assessments; the seventh item is the result of the patient's % predicted 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 score of 0 indicates good asthma control; higher scores indicate increasingly poorer asthma control. Negative change from baseline scores indicate improvement in asthma control.

Outcome measures

Measure	Placebo n=97 Participants Placebo intravenous injection every 4 weeks for a total of 4 doses.	Reslizumab 3.0 mg/kg n=394 Participants Reslizumab intravenous injection at a dosage of 3.0 mg/kg every 4 weeks for a total of 4 doses.
Change From Baseline in Asthma Control Questionnaire (ACQ) at Weeks 4, 8, 12 and 16 Week 4 (n=96, 385)	-0.502 units on a scale Standard Error 0.0710	-0.585 units on a scale Standard Error 0.0375
Change From Baseline in Asthma Control Questionnaire (ACQ) at Weeks 4, 8, 12 and 16 Week 8 (n=93, 377)	-0.631 units on a scale Standard Error 0.0807	-0.701 units on a scale Standard Error 0.0420
Change From Baseline in Asthma Control Questionnaire (ACQ) at Weeks 4, 8, 12 and 16 Week 12 (n=90, 357)	-0.674 units on a scale Standard Error 0.0843	-0.818 units on a scale Standard Error 0.0439
Change From Baseline in Asthma Control Questionnaire (ACQ) at Weeks 4, 8, 12 and 16 Week 16 (n=83, 343)	-0.648 units on a scale Standard Error 0.0878	-0.844 units on a scale Standard Error 0.0453

SECONDARY outcome

Timeframe: Day 1 to Week 28

Population: The safety analysis set includes all patients who took at least 1 dose of study drug, regardless of whether the patients were randomized.

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

Measure	Placebo n=97 Participants Placebo intravenous injection every 4 weeks for a total of 4 doses.	Reslizumab 3.0 mg/kg n=395 Participants Reslizumab intravenous injection at a dosage of 3.0 mg/kg every 4 weeks for a total of 4 doses.
Participants With Treatment-Emergent Adverse Events Any adverse event	72 participants	218 participants
Participants With Treatment-Emergent Adverse Events Severe adverse event	10 participants	25 participants
Participants With Treatment-Emergent Adverse Events Treatment-related adverse event	16 participants	28 participants
Participants With Treatment-Emergent Adverse Events Deaths	0 participants	0 participants
Participants With Treatment-Emergent Adverse Events Serious AEs other than death	4 participants	16 participants
Participants With Treatment-Emergent Adverse Events Treatment-related serious AE	0 participants	2 participants
Participants With Treatment-Emergent Adverse Events Withdrawn from study due to adverse events	12 participants	29 participants
Participants With Treatment-Emergent Adverse Events Withdrawn from study due to treatment-related AE	1 participants	3 participants

SECONDARY outcome

Timeframe: Week 4 to Week 16

Population: Safety analysis set with assessments

Data represents participants with potentially clinically significant (PCS) abnormal serum chemistry, hematology, and urinalysis values during any of the lab tests conducted during the treatment period.

Significance criteria:

• Blood urea nitrogen: >=10.71 mmol/L
• Creatinine: >=177 μmol/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 4-49 U/L.
• Total bilirubin: >=34.2 μmol/L
• Creatinine phosphokinase: >5*ULN. Normal range is 24-207 U/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
• Platelets: <=75 10^9/L
• Absolute neutrophil count: <=1.0 10^9/L
• Urinalysis: blood, glucose, ketones and total protein: >=2 unit increase from baseline

Outcome measures

Measure	Placebo n=97 Participants Placebo intravenous injection every 4 weeks for a total of 4 doses.	Reslizumab 3.0 mg/kg n=393 Participants Reslizumab intravenous injection at a dosage of 3.0 mg/kg every 4 weeks for a total of 4 doses.
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Atleast 1 PCS abnormal serum blood chemistry value	8 participants	26 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Blood urea nitrogen	0 participants	7 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Creatinine	0 participants	1 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Uric acid	1 participants	7 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Aspartate aminotransferase	1 participants	3 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 GGT	2 participants	11 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Total bilirubin	1 participants	0 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Creatinine phosphokinase	1 participants	11 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values At least 1 PCS abnormal hematology value	4 participants	30 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values White blood cells - low	0 participants	6 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values White blood cells - high	0 participants	4 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Hemoglobin	0 participants	10 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Hematocrit	1 participants	19 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Platelets	0 participants	1 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Absolute neutrophil count	3 participants	7 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values At least 1 PCS abnormal urinalysis value	23 participants	94 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Blood (hemoglobin)	6 participants	40 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Glucose	3 participants	17 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Ketones	6 participants	7 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values Total protein	11 participants	43 participants

SECONDARY outcome

Timeframe: Week 4 to Week 28

Population: Safety analysis set of participants with assessments

Data represents participants with potentially clinically significant (PCS) vital sign values during any of the treatment period exams.

Significance criteria

• Heart rate - high: >100 and increase of >= 30 beats/minute (bpm)
• Sitting systolic blood pressure - high: >160 and increase of >=30 mmHg
• Sitting systolic blood pressure - low: <90 and decrease of >=30 mmHg
• Sitting diastolic blood pressure - high: >100 and increase of >=12 mmHg
• Sitting diastolic blood pressure - low: <50 and decrease of >=12 mmHg
• Body temperature - high: >100.5° Fahrenheit or 38.1° Celsius and increase of >2°
• Body temperature - low: <96.5° Fahrenheit or <35.8° Celsius

Outcome measures

Measure	Placebo n=97 Participants Placebo intravenous injection every 4 weeks for a total of 4 doses.	Reslizumab 3.0 mg/kg n=394 Participants Reslizumab intravenous injection at a dosage of 3.0 mg/kg every 4 weeks for a total of 4 doses.
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values At least 1 PCS abnormality	7 participants	43 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values Heart rate	0 participants	4 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values Sitting systolic blood pressure - high	1 participants	6 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values Sitting systolic blood pressure - low	1 participants	4 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values Sitting diastolic blood pressure - high	2 participants	3 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values Sitting diastolic blood pressure - low	0 participants	2 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values Body temperature - high	1 participants	2 participants
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values Body temperature - low	2 participants	25 participants

SECONDARY outcome

Timeframe: Week 16 or endpoint

Population: Safety analysis set

Counts represent the number of participants with potentially clinically significant ECG abnormalities as assessed by the investigator.

Outcome measures

Measure	Placebo n=97 Participants Placebo intravenous injection every 4 weeks for a total of 4 doses.	Reslizumab 3.0 mg/kg n=395 Participants Reslizumab intravenous injection at a dosage of 3.0 mg/kg every 4 weeks for a total of 4 doses.
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Electrocardiogram (ECG) Abnormalities	0 participants	1 participants

SECONDARY outcome

Timeframe: Screening (Week -3), Weeks 8 and 16

Population: Safety analysis set; antibody assessments reported for active treatment arm only.

Counts of participants with a positive anti-drug antibody (ADA) response during treatment is offered for the experimental treatment arm. Blood samples were collected for determination of ADAs before study drug infusion at screening, weeks 8 and 16 or early withdrawal. 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.

Counts represent the total number of participants at each time point with a positive immunogenicity test, and not 'new' participants with a positive test. An overall status of positive includes participants who had a positive ADA at any time point.

Outcome measures

Measure	Placebo Placebo intravenous injection every 4 weeks for a total of 4 doses.	Reslizumab 3.0 mg/kg n=395 Participants Reslizumab intravenous injection at a dosage of 3.0 mg/kg every 4 weeks for a total of 4 doses.
Participants With a Positive Anti-Reslizumab Antibody Status During Study Overall status - negative	—	376 participants
Participants With a Positive Anti-Reslizumab Antibody Status During Study Overall status - positive	—	19 participants
Participants With a Positive Anti-Reslizumab Antibody Status During Study Screening status - negative	—	375 participants
Participants With a Positive Anti-Reslizumab Antibody Status During Study Screening status - positive	—	13 participants
Participants With a Positive Anti-Reslizumab Antibody Status During Study Week 8 - negative	—	346 participants
Participants With a Positive Anti-Reslizumab Antibody Status During Study Week 8 - positive	—	15 participants
Participants With a Positive Anti-Reslizumab Antibody Status During Study Week 16 - negative	—	328 participants
Participants With a Positive Anti-Reslizumab Antibody Status During Study Week 16 - positive	—	9 participants
Participants With a Positive Anti-Reslizumab Antibody Status During Study Endpoint - negative	—	375 participants
Participants With a Positive Anti-Reslizumab Antibody Status During Study Endpoint - positive	—	10 participants

Adverse Events

Placebo

Serious events: 4 serious events

Other events: 41 other events

Deaths: 0 deaths

Reslizumab 3.0 mg/kg

Serious events: 16 serious events

Other events: 118 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=97 participants at risk Placebo intravenous injection every 4 weeks for a total of 4 doses.	Reslizumab 3.0 mg/kg n=395 participants at risk Reslizumab intravenous injection at a dosage of 3.0 mg/kg every 4 weeks for a total of 4 doses.
Gastrointestinal disorders Neurogenic bowel	0.00% 0/97 • Day 1 to Week 28	0.25% 1/395 • Number of events 1 • Day 1 to Week 28
General disorders Non-cardiac chest pain	0.00% 0/97 • Day 1 to Week 28	0.25% 1/395 • Number of events 1 • Day 1 to Week 28
Immune system disorders Anaphylactic reaction	0.00% 0/97 • Day 1 to Week 28	0.51% 2/395 • Number of events 2 • Day 1 to Week 28
Infections and infestations Arthritis infective	0.00% 0/97 • Day 1 to Week 28	0.25% 1/395 • Number of events 1 • Day 1 to Week 28
Infections and infestations Cellulitis	1.0% 1/97 • Number of events 1 • Day 1 to Week 28	0.00% 0/395 • Day 1 to Week 28
Infections and infestations Lower respiratory tract infection	0.00% 0/97 • Day 1 to Week 28	0.25% 1/395 • Number of events 1 • Day 1 to Week 28
Infections and infestations Pneumonia	0.00% 0/97 • Day 1 to Week 28	0.25% 1/395 • Number of events 1 • Day 1 to Week 28
Injury, poisoning and procedural complications Fall	0.00% 0/97 • Day 1 to Week 28	0.25% 1/395 • Number of events 1 • Day 1 to Week 28
Injury, poisoning and procedural complications Tibia fracture	0.00% 0/97 • Day 1 to Week 28	0.25% 1/395 • Number of events 1 • Day 1 to Week 28
Metabolism and nutrition disorders Diabetic ketoacidosis	1.0% 1/97 • Number of events 1 • Day 1 to Week 28	0.00% 0/395 • Day 1 to Week 28
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.00% 0/97 • Day 1 to Week 28	0.25% 1/395 • Number of events 1 • Day 1 to Week 28
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/97 • Day 1 to Week 28	0.25% 1/395 • Number of events 1 • Day 1 to Week 28
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/97 • Day 1 to Week 28	0.25% 1/395 • Number of events 1 • Day 1 to Week 28
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.00% 0/97 • Day 1 to Week 28	0.25% 1/395 • Number of events 1 • Day 1 to Week 28
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.00% 0/97 • Day 1 to Week 28	0.25% 1/395 • Number of events 1 • Day 1 to Week 28
Nervous system disorders Cerebral vasoconstriction	0.00% 0/97 • Day 1 to Week 28	0.25% 1/395 • Number of events 1 • Day 1 to Week 28
Nervous system disorders Lumbar radiculopathy	0.00% 0/97 • Day 1 to Week 28	0.25% 1/395 • Number of events 1 • Day 1 to Week 28
Nervous system disorders Syncope	0.00% 0/97 • Day 1 to Week 28	0.25% 1/395 • Number of events 1 • Day 1 to Week 28
Nervous system disorders VIIth nerve paralysis	0.00% 0/97 • Day 1 to Week 28	0.25% 1/395 • Number of events 1 • Day 1 to Week 28
Respiratory, thoracic and mediastinal disorders Asthma	2.1% 2/97 • Number of events 2 • Day 1 to Week 28	1.3% 5/395 • Number of events 6 • Day 1 to Week 28
Respiratory, thoracic and mediastinal disorders Status asthmaticus	0.00% 0/97 • Day 1 to Week 28	0.25% 1/395 • Number of events 2 • Day 1 to Week 28

Other adverse events

Measure	Placebo n=97 participants at risk Placebo intravenous injection every 4 weeks for a total of 4 doses.	Reslizumab 3.0 mg/kg n=395 participants at risk Reslizumab intravenous injection at a dosage of 3.0 mg/kg every 4 weeks for a total of 4 doses.
Gastrointestinal disorders Nausea	5.2% 5/97 • Number of events 6 • Day 1 to Week 28	0.76% 3/395 • Number of events 3 • Day 1 to Week 28
Infections and infestations Bronchitis	6.2% 6/97 • Number of events 7 • Day 1 to Week 28	3.5% 14/395 • Number of events 14 • Day 1 to Week 28
Infections and infestations Nasopharyngitis	5.2% 5/97 • Number of events 5 • Day 1 to Week 28	3.3% 13/395 • Number of events 15 • Day 1 to Week 28
Infections and infestations Sinusitis	7.2% 7/97 • Number of events 7 • Day 1 to Week 28	5.6% 22/395 • Number of events 26 • Day 1 to Week 28
Infections and infestations Upper respiratory tract infection	11.3% 11/97 • Number of events 13 • Day 1 to Week 28	10.6% 42/395 • Number of events 50 • Day 1 to Week 28
Respiratory, thoracic and mediastinal disorders Asthma	18.6% 18/97 • Number of events 20 • Day 1 to Week 28	12.2% 48/395 • Number of events 58 • Day 1 to Week 28

Additional Information

Director, Clinical Research

Teva Branded Pharmaceutical Products, R&D Inc.

Phone: 215-591-3000

Email: ustevatrials@tevapharm.com

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