Trial Outcomes & Findings for A Study of Reslizumab in Patients 12 Years of Age and Older With Severe Eosinophilic Asthma (NCT NCT03052725)

NCT ID: NCT03052725

Last Updated: 2022-12-14

Results Overview

An adverse event is any untoward medical occurrence, regardless of whether it has a causal relationship with study treatment. In this study, asthma exacerbations should not be recorded as adverse events unless assessed by the investigator as more severe than the patient's usual disease course. The period for reporting treatment-emergent adverse events was defined as the period after the first dose of study drug was administered until the end of treatment visit. 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.

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 391 participants
• Primary outcome timeframe: Day 1 to up to Day 269; for participants who discontinued early for reasons other than study termination, the timeframe was first dose of study drug to 4 weeks after the last dose of study drug.
• Results posted on: 2022-12-14

Participant Flow

A total of 392 patients with severe eosinophilic asthma rolled over from Study 30025 or 30027, and 391 of these patients (at 125 centers) were enrolled into this extension study and treated with reslizumab. One patient withdrew consent after completing Study 30025 and before enrolling in Study 30066.

Of the 391 patients enrolled, 112 (29%) enrolled seamlessly and 279 (71%) enrolled non-seamlessly, meaning there was a time gap between completion of the parent study and start of this extension study.

Participant milestones

Measure	Reslizumab 110 mg; Previous Treatment Placebo Participants who were administered placebo in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.	Reslizumab 110 mg: Previous Treatment Reslizumab Participants who were administered reslizumab in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.
Overall Study STARTED	194	197
Overall Study Safety Analysis Set	194	196
Overall Study COMPLETED	46	47
Overall Study NOT COMPLETED	148	150

Reasons for withdrawal

Measure	Reslizumab 110 mg; Previous Treatment Placebo Participants who were administered placebo in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.	Reslizumab 110 mg: Previous Treatment Reslizumab Participants who were administered reslizumab in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.
Overall Study Adverse Event	2	0
Overall Study Withdrawal by Subject	3	4
Overall Study Pregnancy	0	1
Overall Study Site closure	0	1
Overall Study Study terminated by sponsor	143	144

Baseline Characteristics

Some participants were missing a baseline weight measurement.

Baseline characteristics by cohort

Measure	Reslizumab 110 mg; Previous Treatment Placebo n=194 Participants Participants who were administered placebo in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.	Reslizumab 110 mg: Previous Treatment Reslizumab n=197 Participants Participants who were administered reslizumab in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.	Total n=391 Participants Total of all reporting groups
Age, Continuous	50.4 years STANDARD_DEVIATION 14.85 • n=194 Participants	52.5 years STANDARD_DEVIATION 15.62 • n=197 Participants	51.5 years STANDARD_DEVIATION 15.26 • n=391 Participants
Age, Customized 12 to <18 years	9 Participants n=194 Participants	8 Participants n=197 Participants	17 Participants n=391 Participants
Age, Customized 18 to <65 years	156 Participants n=194 Participants	141 Participants n=197 Participants	297 Participants n=391 Participants
Age, Customized >=65 years	29 Participants n=194 Participants	48 Participants n=197 Participants	77 Participants n=391 Participants
Sex: Female, Male Female	112 Participants n=194 Participants	122 Participants n=197 Participants	234 Participants n=391 Participants
Sex: Female, Male Male	82 Participants n=194 Participants	75 Participants n=197 Participants	157 Participants n=391 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	18 Participants n=194 Participants	8 Participants n=197 Participants	26 Participants n=391 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	174 Participants n=194 Participants	187 Participants n=197 Participants	361 Participants n=391 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=194 Participants	2 Participants n=197 Participants	4 Participants n=391 Participants
Race/Ethnicity, Customized White	182 Participants n=194 Participants	185 Participants n=197 Participants	367 Participants n=391 Participants
Race/Ethnicity, Customized Black	7 Participants n=194 Participants	10 Participants n=197 Participants	17 Participants n=391 Participants
Race/Ethnicity, Customized Asian	3 Participants n=194 Participants	2 Participants n=197 Participants	5 Participants n=391 Participants
Race/Ethnicity, Customized Other	2 Participants n=194 Participants	0 Participants n=197 Participants	2 Participants n=391 Participants
Weight	79.78 kg STANDARD_DEVIATION 17.647 • n=186 Participants • Some participants were missing a baseline weight measurement.	81.22 kg STANDARD_DEVIATION 18.712 • n=184 Participants • Some participants were missing a baseline weight measurement.	80.49 kg STANDARD_DEVIATION 18.174 • n=370 Participants • Some participants were missing a baseline weight measurement.
Body Mass Index (BMI)	28.377 kg/m^2 STANDARD_DEVIATION 5.8288 • n=184 Participants • Some participants were missing a baseline BMI measure.	28.880 kg/m^2 STANDARD_DEVIATION 5.9672 • n=182 Participants • Some participants were missing a baseline BMI measure.	28.627 kg/m^2 STANDARD_DEVIATION 5.8954 • n=366 Participants • Some participants were missing a baseline BMI measure.
Systemic Corticosteroid (OCS) Use at Baseline	12.01 mg prednisolone or equivalent STANDARD_DEVIATION 10.870 • n=46 Participants • Safety Analysis set of participants on daily OCS at baseline	12.26 mg prednisolone or equivalent STANDARD_DEVIATION 10.760 • n=45 Participants • Safety Analysis set of participants on daily OCS at baseline	12.14 mg prednisolone or equivalent STANDARD_DEVIATION 10.756 • n=91 Participants • Safety Analysis set of participants on daily OCS at baseline
Region Group U.S./Canada	47 Participants n=194 Participants • Enrolled analysis set	41 Participants n=197 Participants • Enrolled analysis set	88 Participants n=391 Participants • Enrolled analysis set
Region Group Europe	131 Participants n=194 Participants • Enrolled analysis set	136 Participants n=197 Participants • Enrolled analysis set	267 Participants n=391 Participants • Enrolled analysis set
Region Group Other	16 Participants n=194 Participants • Enrolled analysis set	20 Participants n=197 Participants • Enrolled analysis set	36 Participants n=391 Participants • Enrolled analysis set

PRIMARY outcome

Timeframe: Day 1 to up to Day 269; for participants who discontinued early for reasons other than study termination, the timeframe was first dose of study drug to 4 weeks after the last dose of study drug.

Population: Safety analysis set

An adverse event is any untoward medical occurrence, regardless of whether it has a causal relationship with study treatment. In this study, asthma exacerbations should not be recorded as adverse events unless assessed by the investigator as more severe than the patient's usual disease course. The period for reporting treatment-emergent adverse events was defined as the period after the first dose of study drug was administered until the end of treatment visit. 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	Reslizumab 110 mg; Previous Treatment Placebo n=194 Participants Participants who were administered placebo in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.	Reslizumab 110 mg; Previous Treatment Reslizumab n=196 Participants Participants who were administered reslizumab in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.
Participants With Treatment-Emergent Adverse Events (TEAEs) >=1 serious TEAE	5 Participants	11 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) >=1 TEAE	102 Participants	114 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) >=1 treatment-related TEAE	7 Participants	6 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) >=1 treatment-related, serious TEAE	0 Participants	0 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) >=1 TEAE leading to discontinuation	2 Participants	0 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) >=1 TEAE leading to death	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Week 0 (baseline), Weeks 8, 24, 36 plus any unscheduled visits

Population: Safety analysis set of participants with a baseline and post-baseline result for each variable

Participants are included in the counts if the worst study value reaches the following clinically significant levels:

Eosinophils (high): >=1.5*10^9/L and increase >0 Hematocrit (low): >=18 years old: <0.32 L/L for females; <0.37 L/L for males plus a decrease >0 for both or 12 to <18 years old: <0.30 L/L and a decrease >0 for both females and males Hemoglobin (low): >=18 years old: <=95 g/L and decrease >0; 12 to <18 years old: <=100 g/L and decrease >0 Leukocytes (high): >=20*10^9/L and increase >0 Leukocytes (low): <=3*10^9/L and decrease >0 Neutrophils (low): <=1*10^9/L and decrease >0 Platelets (low): <=75*10^9/L and decrease >0

Outcome measures

Measure	Reslizumab 110 mg; Previous Treatment Placebo n=192 Participants Participants who were administered placebo in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.	Reslizumab 110 mg; Previous Treatment Reslizumab n=192 Participants Participants who were administered reslizumab in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.
Participants With Potentially Clinically Significant Abnormal Hematology Values Eosinophils (high)	1 Participants	0 Participants
Participants With Potentially Clinically Significant Abnormal Hematology Values Participants with >=1 abnormality	8 Participants	5 Participants
Participants With Potentially Clinically Significant Abnormal Hematology Values Hematocrit (low)	4 Participants	2 Participants
Participants With Potentially Clinically Significant Abnormal Hematology Values Hemoglobin (low)	2 Participants	0 Participants
Participants With Potentially Clinically Significant Abnormal Hematology Values Leukocytes (high)	0 Participants	1 Participants
Participants With Potentially Clinically Significant Abnormal Hematology Values Leukocytes (low)	2 Participants	0 Participants
Participants With Potentially Clinically Significant Abnormal Hematology Values Neutrophils (low)	1 Participants	1 Participants
Participants With Potentially Clinically Significant Abnormal Hematology Values Platelets	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Week 0 (baseline), Weeks 4, 8, 24, 36 plus any unscheduled visits

Population: Safety analysis set of participants with a baseline and post-baseline result for each variable

Participants are included in the counts if the worst study value reaches the following clinically significant levels:

Alanine Aminotransferase (high): >=3* upper limit of normal (ULN) and increase >0 Aspartate Aminotransferase (high): >=3* upper limit of normal (ULN) and increase >0 Bilirubin (high): >=34.2 micromol/L and increase >0 Blood Urea Nitrogen (high): >=10.71 mmol/L and increase >0 Creatine Phosphokinase (high): >10* ULN and increase >0 Creatine Phosphokinase (medium high): >=3.1*ULN and <=10*ULN and increase >0 Creatinine (high): >=177 micromol/L and increase >0

Outcome measures

Measure	Reslizumab 110 mg; Previous Treatment Placebo n=193 Participants Participants who were administered placebo in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.	Reslizumab 110 mg; Previous Treatment Reslizumab n=192 Participants Participants who were administered reslizumab in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.
Participants With Potentially Clinically Significant Abnormal Serum Chemistry Values Participants with >=1 abnormality	12 Participants	10 Participants
Participants With Potentially Clinically Significant Abnormal Serum Chemistry Values Alanine Aminotransferase (high)	1 Participants	2 Participants
Participants With Potentially Clinically Significant Abnormal Serum Chemistry Values Aspartate Aminotransferase (high)	1 Participants	1 Participants
Participants With Potentially Clinically Significant Abnormal Serum Chemistry Values Bilirubin (high)	2 Participants	1 Participants
Participants With Potentially Clinically Significant Abnormal Serum Chemistry Values Blood Urea Nitrogen (high)	2 Participants	4 Participants
Participants With Potentially Clinically Significant Abnormal Serum Chemistry Values Creatine Phosphokinase (high)	2 Participants	1 Participants
Participants With Potentially Clinically Significant Abnormal Serum Chemistry Values Creatine Phosphokinase (medium high)	6 Participants	4 Participants
Participants With Potentially Clinically Significant Abnormal Serum Chemistry Values Creatinine (high)	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, 16, 20, 24, 28, and 36

Population: Safety analysis set

The worst finding for participants in each tolerability and injection site domain from all treatment weeks is summarized. Local tolerability at the injection site was assessed approximately 1 hour after study drug administration.

Severity was rated on a 4-level scale of none, mild, moderate and severe.

Outcome measures

Measure	Reslizumab 110 mg; Previous Treatment Placebo n=194 Participants Participants who were administered placebo in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.	Reslizumab 110 mg; Previous Treatment Reslizumab n=196 Participants Participants who were administered reslizumab in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.
Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity Swelling - None	191 Participants	190 Participants
Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity Pain - None	191 Participants	194 Participants
Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity Pain - Mild	3 Participants	2 Participants
Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity Pain - Moderate	0 Participants	0 Participants
Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity Pain - Severe	0 Participants	0 Participants
Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity Tenderness - None	193 Participants	192 Participants
Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity Tenderness - Mild	1 Participants	4 Participants
Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity Tenderness - Moderate	0 Participants	0 Participants
Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity Tenderness - Severe	0 Participants	0 Participants
Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity Erythema - None	191 Participants	188 Participants
Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity Erythema - Mild	2 Participants	7 Participants
Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity Erythema - Moderate	1 Participants	1 Participants
Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity Erythema - Severe	0 Participants	0 Participants
Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity Warmth - None	192 Participants	192 Participants
Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity Warmth - Mild	1 Participants	4 Participants
Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity Warmth - Moderate	1 Participants	0 Participants
Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity Warmth - Severe	0 Participants	0 Participants
Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity Swelling - Mild	2 Participants	5 Participants
Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity Swelling - Moderate	1 Participants	1 Participants
Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity Swelling - Severe	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Week 0 (baseline), Weeks 4, 8, 12, 16,20, 24, 28, 32, 36 plus any unscheduled visits

Population: Safety analysis set of participants with a baseline and post-baseline result for each variable

Participants are included in the counts if the worst study value reaches the following clinically significant levels:

Diastolic blood pressure (high): >100 mmHg and increase >=12 for participants >=18 years; >85 mmHg and increase >=12 for participants 12 - < 18 years Pulse rate (high): >100 beats/minute and increase >=12 Respiratory rate (high): >24 breaths/minute and increase >=10 for participants >=18 years >20 breaths/minute and increase >=10 for participants 12 - < 18 years Systolic blood pressure (high): >160 mmHg and increase >=30 for participants >=18 years; >130 mmHg and increase >=30 for participants 12 - < 18 years Temperature (high): >38.1 celsius and increase >=1.1 Temperature (low): <35.8 celsius

Outcome measures

Measure	Reslizumab 110 mg; Previous Treatment Placebo n=193 Participants Participants who were administered placebo in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.	Reslizumab 110 mg; Previous Treatment Reslizumab n=196 Participants Participants who were administered reslizumab in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.
Participants With Potentially Clinically Significant Abnormal Vital Sign Values Participants with >=1 abnormality	20 Participants	16 Participants
Participants With Potentially Clinically Significant Abnormal Vital Sign Values Diastolic Blood Pressure - High	0 Participants	1 Participants
Participants With Potentially Clinically Significant Abnormal Vital Sign Values Pulse Rate - High	1 Participants	2 Participants
Participants With Potentially Clinically Significant Abnormal Vital Sign Values Respiratory Rate - High	2 Participants	0 Participants
Participants With Potentially Clinically Significant Abnormal Vital Sign Values Systolic Blood Pressure - High	2 Participants	0 Participants
Participants With Potentially Clinically Significant Abnormal Vital Sign Values Temperature - High	1 Participants	0 Participants
Participants With Potentially Clinically Significant Abnormal Vital Sign Values Temperature - Low	14 Participants	13 Participants

SECONDARY outcome

Timeframe: Day 1 to up to Day 269; for participants who discontinued early for reasons other than study termination, the timeframe was first dose of study drug to 4 weeks after the last dose of study drug.

Population: Safety Analysis set

Data is included between the first dose of study drug to the end of treatment visit for completed participants, and the first dose of study drug to 4 weeks after the last dose of study drug for patients who discontinued treatment early.

Annual rate is defined as the number of events/(duration of treatment [days]/365.25).

Participants with zero events are included.

Outcome measures

Measure	Reslizumab 110 mg; Previous Treatment Placebo n=194 Participants Participants who were administered placebo in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.	Reslizumab 110 mg; Previous Treatment Reslizumab n=196 Participants Participants who were administered reslizumab in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.
Annualized Rate of Clinical Asthma Exacerbations (CAEs)	0.42 CAEs / year Standard Deviation 1.104	0.70 CAEs / year Standard Deviation 1.538

SECONDARY outcome

Timeframe: Day 1 to up to Day 269; for participants who discontinued early for reasons other than study termination, the timeframe was first dose of study drug to 4 weeks after the last dose of study drug.

Population: Safety Analysis set

Data is included between the first dose of study drug to the end of treatment visit for completed participants, and the first dose of study drug to 4 weeks after the last dose of study drug for patients who discontinued treatment early.

Annual rate is defined as the number of events/(duration of treatment [days]/365.25).

Participants with zero events are included.

Outcome measures

Measure	Reslizumab 110 mg; Previous Treatment Placebo n=194 Participants Participants who were administered placebo in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.	Reslizumab 110 mg; Previous Treatment Reslizumab n=196 Participants Participants who were administered reslizumab in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.
Annualized Rate of Clinical Asthma Exacerbations (CAEs) Requiring Asthma-Specific Hospital Admissions or Emergency Room Visits	0.06 CAEs / year Standard Deviation 0.362	0.11 CAEs / year Standard Deviation 0.514

SECONDARY outcome

Timeframe: Day 1 to up to Day 269; for participants who discontinued early for reasons other than study termination, the timeframe was first dose of study drug to 4 weeks after the last dose of study drug

Population: Safety Analysis set

Participants with no hospitalizations are included.

Outcome measures

Measure	Reslizumab 110 mg; Previous Treatment Placebo n=194 Participants Participants who were administered placebo in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.	Reslizumab 110 mg; Previous Treatment Reslizumab n=196 Participants Participants who were administered reslizumab in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.
Mean Number of Days of Hospital Stay During the Treatment Period	0.25 days Standard Deviation 1.658	1.02 days Standard Deviation 7.848

SECONDARY outcome

Timeframe: Day 1 to up to Day 269; for participants who discontinued early for reasons other than study termination, the timeframe was first dose of study drug to 4 weeks after the last dose of study drug

Population: Safety Analysis set

Participants with no school or work days missed due to asthma are included in the counts.

Outcome measures

Measure	Reslizumab 110 mg; Previous Treatment Placebo n=194 Participants Participants who were administered placebo in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.	Reslizumab 110 mg; Previous Treatment Reslizumab n=196 Participants Participants who were administered reslizumab in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.
Mean Number of School/Work Days Missed Due to Asthma During the Treatment Period	0.11 days Standard Deviation 1.202	0.00 days Standard Deviation 0.000

SECONDARY outcome

Timeframe: Week 0 (baseline), Weeks 8, 24, 36

Population: Safety Analysis set

The FEV1 is the volume of air that can be forcibly exhaled from the lungs in the first second, measured in liters.

Pre-bronchodilator spirometry assessments at designated clinic visits (weeks 0, 8, and 24, and 36) should only be performed after withholding short-acting bronchodilators (ie, inhaled short-acting beta-adrenergic agonists and/or short-acting anticholinergics) for at least 6 hours and long-acting bronchodilators ie, inhaled long-acting beta-adrenergic agonists and long acting anticholinergic agents) for at least 12 or 24 hours, according to their labeled dose schedule.

Outcome measures

Measure	Reslizumab 110 mg; Previous Treatment Placebo n=194 Participants Participants who were administered placebo in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.	Reslizumab 110 mg; Previous Treatment Reslizumab n=196 Participants Participants who were administered reslizumab in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.
Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1): Baseline Values and Change From Baseline Values at Weeks 8, 24 and 36 Baseline - observed value	2.162 liters Standard Deviation 0.980	2.117 liters Standard Deviation 0.927
Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1): Baseline Values and Change From Baseline Values at Weeks 8, 24 and 36 Change at Week 8	0.099 liters Standard Deviation 0.704	0.031 liters Standard Deviation 0.529
Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1): Baseline Values and Change From Baseline Values at Weeks 8, 24 and 36 Change at Week 24	0.169 liters Standard Deviation 0.851	-0.020 liters Standard Deviation 0.472
Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1): Baseline Values and Change From Baseline Values at Weeks 8, 24 and 36 Change at Week 36	0.245 liters Standard Deviation 0.677	0.010 liters Standard Deviation 0.550

SECONDARY outcome

Timeframe: Week 0 (baseline), Weeks 1, 4, 8, 24, 36

Population: Safety analysis set

A weekly average of daily morning ambulatory FEV1 (measured by the handheld spirometry device) was derived using 7-day window intervals. The average was calculated as the sum of all values divided by the number of non-missing assessments. There will be no imputation of missing data. At least 4 of the 7 measurements need to be recorded for a week to be included in the analysis; otherwise the week was treated as missing.

Outcome measures

Measure	Reslizumab 110 mg; Previous Treatment Placebo n=194 Participants Participants who were administered placebo in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.	Reslizumab 110 mg; Previous Treatment Reslizumab n=196 Participants Participants who were administered reslizumab in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.
Morning Ambulatory Forced Expiratory Volume in One Second (FEV1): Baseline Values and Change From Baseline Values at Weeks 1, 4, 8, 24 and 36 Baseline - observed value	2.057 liters Standard Deviation 0.814	2.027 liters Standard Deviation 0.847
Morning Ambulatory Forced Expiratory Volume in One Second (FEV1): Baseline Values and Change From Baseline Values at Weeks 1, 4, 8, 24 and 36 Change at Week 1	0.002 liters Standard Deviation 0.345	-0.044 liters Standard Deviation 0.291
Morning Ambulatory Forced Expiratory Volume in One Second (FEV1): Baseline Values and Change From Baseline Values at Weeks 1, 4, 8, 24 and 36 Change at Week 4	0.051 liters Standard Deviation 0.490	-0.049 liters Standard Deviation 0.319
Morning Ambulatory Forced Expiratory Volume in One Second (FEV1): Baseline Values and Change From Baseline Values at Weeks 1, 4, 8, 24 and 36 Change at Week 8	0.028 liters Standard Deviation 0.463	-0.039 liters Standard Deviation 0.345
Morning Ambulatory Forced Expiratory Volume in One Second (FEV1): Baseline Values and Change From Baseline Values at Weeks 1, 4, 8, 24 and 36 Change at Week 24	0.051 liters Standard Deviation 0.492	-0.062 liters Standard Deviation 0.403
Morning Ambulatory Forced Expiratory Volume in One Second (FEV1): Baseline Values and Change From Baseline Values at Weeks 1, 4, 8, 24 and 36 Change at Week 36	0.061 liters Standard Deviation 0.273	-0.053 liters Standard Deviation 0.465

SECONDARY outcome

Timeframe: Week 0 (baseline), Weeks 16-20, Weeks 32-36

Population: Safety Analysis set of participants on daily OCS at baseline

Daily OCS dose is defined as total OCS dose in a day (accounting for reported dose and dose frequency) and converting the total daily dose to a prednisone-equivalent dose.

Baseline dose is the prescribed OCS dose on the day of first dose of study drug in this study. Dose at Weeks 16-20 and 32-36 is the mean of all daily OCS doses during the week range.

Percent change = 100 * (absolute change / baseline dose)

Outcome measures

Measure	Reslizumab 110 mg; Previous Treatment Placebo n=46 Participants Participants who were administered placebo in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.	Reslizumab 110 mg; Previous Treatment Reslizumab n=45 Participants Participants who were administered reslizumab in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.
Percent Change From Baseline in Daily Oral Corticosteroid (OCS) Dose During Weeks 16-20 and Weeks 32-36 % change at Week 16-20	-2.19 percent change Standard Deviation 51.347	-6.96 percent change Standard Deviation 40.904
Percent Change From Baseline in Daily Oral Corticosteroid (OCS) Dose During Weeks 16-20 and Weeks 32-36 % change at Week 32-36	-8.44 percent change Standard Deviation 24.236	-8.75 percent change Standard Deviation 29.666

SECONDARY outcome

Timeframe: Baseline (Week 0), Weeks 1, 4, 8, 24, 36

Population: Safety Analysis set

Total inhalations of reliever bronchodilator medication (eg, short-acting beta-agonist [SABA]) measured using weekly averages.

The average was calculated as the sum of all values divided by the number of non-missing assessments. There was no imputation of missing data. At least 4 of the 7 measurements need to be recorded for a week to be included in the analysis; otherwise the week was treated as missing.

Outcome measures

Measure	Reslizumab 110 mg; Previous Treatment Placebo n=194 Participants Participants who were administered placebo in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.	Reslizumab 110 mg; Previous Treatment Reslizumab n=196 Participants Participants who were administered reslizumab in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.
Total Inhalations of Reliever Bronchodilator Medication: Baseline Values and Change From Baseline Values at Weeks 1, 4, 8, 24 and 36 Baseline - observed values	2.4 inhalations Standard Deviation 3.39	2.6 inhalations Standard Deviation 3.10
Total Inhalations of Reliever Bronchodilator Medication: Baseline Values and Change From Baseline Values at Weeks 1, 4, 8, 24 and 36 Change at Week 1	-0.4 inhalations Standard Deviation 1.30	-0.4 inhalations Standard Deviation 1.17
Total Inhalations of Reliever Bronchodilator Medication: Baseline Values and Change From Baseline Values at Weeks 1, 4, 8, 24 and 36 Change at Week 4	-0.6 inhalations Standard Deviation 1.86	-0.5 inhalations Standard Deviation 1.50
Total Inhalations of Reliever Bronchodilator Medication: Baseline Values and Change From Baseline Values at Weeks 1, 4, 8, 24 and 36 Change at Week 8	-0.7 inhalations Standard Deviation 1.79	-0.6 inhalations Standard Deviation 1.61
Total Inhalations of Reliever Bronchodilator Medication: Baseline Values and Change From Baseline Values at Weeks 1, 4, 8, 24 and 36 Change at Week 24	-0.8 inhalations Standard Deviation 1.92	-0.8 inhalations Standard Deviation 1.78
Total Inhalations of Reliever Bronchodilator Medication: Baseline Values and Change From Baseline Values at Weeks 1, 4, 8, 24 and 36 Change at Week 36	-0.5 inhalations Standard Deviation 1.69	-0.6 inhalations Standard Deviation 1.80

SECONDARY outcome

Timeframe: Baseline (Week 0), Weeks 8, 24, 36

Population: Safety analysis set

The ACQ-6 is a validated asthma assessment tool that has been widely used. There are 6 self-assessment questions. Each item on the ACQ-6 has a possible score ranging from 0 to 6 and the total score is the mean of all responses. The seven-point response scale: 0 = 'totally controlled' and 6 = 'severely uncontrolled.' Negative change from baseline values indicate improved asthma control.

Outcome measures

Measure	Reslizumab 110 mg; Previous Treatment Placebo n=194 Participants Participants who were administered placebo in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.	Reslizumab 110 mg; Previous Treatment Reslizumab n=196 Participants Participants who were administered reslizumab in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.
Asthma Control Questionnaire-6 (ACQ-6) Total Score: Baseline Values and Change From Baseline Values at Weeks 8, 24 and 36 Change at Week 36	-0.34 units on a scale Standard Deviation 0.855	-0.28 units on a scale Standard Deviation 0.867
Asthma Control Questionnaire-6 (ACQ-6) Total Score: Baseline Values and Change From Baseline Values at Weeks 8, 24 and 36 Baseline - observed values	1.72 units on a scale Standard Deviation 1.098	1.69 units on a scale Standard Deviation 1.171
Asthma Control Questionnaire-6 (ACQ-6) Total Score: Baseline Values and Change From Baseline Values at Weeks 8, 24 and 36 Change at Week 8	-0.31 units on a scale Standard Deviation 0.777	-0.20 units on a scale Standard Deviation 0.718
Asthma Control Questionnaire-6 (ACQ-6) Total Score: Baseline Values and Change From Baseline Values at Weeks 8, 24 and 36 Change at Week 24	-0.30 units on a scale Standard Deviation 0.936	-0.23 units on a scale Standard Deviation 0.771

SECONDARY outcome

Timeframe: Baseline (Week 0), Weeks 8, 24, 36

Population: Safety Analysis set of participants age 12-70 years

The AQLQ +12 is a modified version of the standardized AQLQ, which was developed to measure functional impairments experienced by adults ≥17 years of age. The AQLQ +12 is valid for patients 12 to 70 years of age and includes 32 questions in 4 domains (symptoms, activity limitation, emotional function, and environmental stimuli). Participants were asked to recall their experiences during the previous 2 weeks and score each of the questions on a 7-point scale, where 7=not at all limited and 1=totally limited. The overall score of the AQLQ +12 was derived as the average of the 32 questions, thus, the total score ranges from 1 (indicates "total impairment") to 7 (indicates "no impairment").

Positive change from baseline values indicate improved quality of life.

Outcome measures

Measure	Reslizumab 110 mg; Previous Treatment Placebo n=187 Participants Participants who were administered placebo in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.	Reslizumab 110 mg; Previous Treatment Reslizumab n=179 Participants Participants who were administered reslizumab in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.
Asthma Quality of Life Questionnaire Administered to Participants Ages 12-70 Years (AQLQ +12) Overall Score: Baseline Values and Change From Baseline Values at Weeks 8, 24 and 36 Baseline - observed value	5.04 units on a scale Standard Deviation 1.249	5.14 units on a scale Standard Deviation 1.270
Asthma Quality of Life Questionnaire Administered to Participants Ages 12-70 Years (AQLQ +12) Overall Score: Baseline Values and Change From Baseline Values at Weeks 8, 24 and 36 Change at Week 8	0.30 units on a scale Standard Deviation 0.716	0.14 units on a scale Standard Deviation 0.700
Asthma Quality of Life Questionnaire Administered to Participants Ages 12-70 Years (AQLQ +12) Overall Score: Baseline Values and Change From Baseline Values at Weeks 8, 24 and 36 Change at Week 24	0.28 units on a scale Standard Deviation 0.727	0.20 units on a scale Standard Deviation 0.830
Asthma Quality of Life Questionnaire Administered to Participants Ages 12-70 Years (AQLQ +12) Overall Score: Baseline Values and Change From Baseline Values at Weeks 8, 24 and 36 Change at Week 36	0.32 units on a scale Standard Deviation 0.835	0.19 units on a scale Standard Deviation 0.948

SECONDARY outcome

Timeframe: Baseline - date of randomization in the previous study (C38072-AS-30025 or C38072-AS-30027), Weeks 8, 24, 36 or early withdrawal

Population: Safety Analysis set

Treatment-emergent responses were defined as a positive sample post-baseline (negative baseline) OR a titer increase of >=4-fold relative to a positive baseline sample.

Two types of antibody assay were performed, an immunogenicity status assay (ADA) and neutralizing assay (NAb).

The ADA assay produces a positive or negative result. For samples with a positive result, a neutralizing assay was performed, which also produces a positive or negative result.

Outcome measures

Measure	Reslizumab 110 mg; Previous Treatment Placebo n=194 Participants Participants who were administered placebo in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.	Reslizumab 110 mg; Previous Treatment Reslizumab n=196 Participants Participants who were administered reslizumab in the parent study, were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.
Participants With Treatment-Emergent Anti-Drug Antibody (ADA) Responses	11 Participants	9 Participants

SECONDARY outcome

Timeframe: Week 51

Population: Safety Analysis set

The endpoint was defined to evaluate immunogenicity after study drug washout since the end of study visit on Week 51 was to be 19 weeks after the final dose of study drug. Due to the early termination of the study no participants had an end of study visit.

Outcome measures

Outcome data not reported

Adverse Events

Reslizumab 110 mg

Serious events: 16 serious events

Other events: 70 other events

Deaths: 0 deaths

Serious adverse events

Measure	Reslizumab 110 mg n=390 participants at risk Participants were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.
Gastrointestinal disorders Abdominal distension	0.26% 1/390 • Number of events 1 • Day 1 to up to Day 269; for participants who discontinued early for reasons other than study termination, the timeframe was first dose of study drug to 4 weeks after the last dose of study drug.
Gastrointestinal disorders Dysphagia	0.26% 1/390 • Number of events 1 • Day 1 to up to Day 269; for participants who discontinued early for reasons other than study termination, the timeframe was first dose of study drug to 4 weeks after the last dose of study drug.
Gastrointestinal disorders Inguinal hernia	0.26% 1/390 • Number of events 1 • Day 1 to up to Day 269; for participants who discontinued early for reasons other than study termination, the timeframe was first dose of study drug to 4 weeks after the last dose of study drug.
Gastrointestinal disorders Vomiting	0.26% 1/390 • Number of events 1 • Day 1 to up to Day 269; for participants who discontinued early for reasons other than study termination, the timeframe was first dose of study drug to 4 weeks after the last dose of study drug.
General disorders Chest pain	0.26% 1/390 • Number of events 1 • Day 1 to up to Day 269; for participants who discontinued early for reasons other than study termination, the timeframe was first dose of study drug to 4 weeks after the last dose of study drug.
Infections and infestations Appendicitis	0.26% 1/390 • Number of events 1 • Day 1 to up to Day 269; for participants who discontinued early for reasons other than study termination, the timeframe was first dose of study drug to 4 weeks after the last dose of study drug.
Infections and infestations Influenza	0.26% 1/390 • Number of events 1 • Day 1 to up to Day 269; for participants who discontinued early for reasons other than study termination, the timeframe was first dose of study drug to 4 weeks after the last dose of study drug.
Infections and infestations Peritonsillar abscess	0.26% 1/390 • Number of events 1 • Day 1 to up to Day 269; for participants who discontinued early for reasons other than study termination, the timeframe was first dose of study drug to 4 weeks after the last dose of study drug.
Infections and infestations Pneumonia	0.77% 3/390 • Number of events 3 • Day 1 to up to Day 269; for participants who discontinued early for reasons other than study termination, the timeframe was first dose of study drug to 4 weeks after the last dose of study drug.
Injury, poisoning and procedural complications Post procedural haematoma	0.26% 1/390 • Number of events 1 • Day 1 to up to Day 269; for participants who discontinued early for reasons other than study termination, the timeframe was first dose of study drug to 4 weeks after the last dose of study drug.
Musculoskeletal and connective tissue disorders Neck pain	0.26% 1/390 • Number of events 1 • Day 1 to up to Day 269; for participants who discontinued early for reasons other than study termination, the timeframe was first dose of study drug to 4 weeks after the last dose of study drug.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.26% 1/390 • Number of events 1 • Day 1 to up to Day 269; for participants who discontinued early for reasons other than study termination, the timeframe was first dose of study drug to 4 weeks after the last dose of study drug.
Musculoskeletal and connective tissue disorders Synovial cyst	0.26% 1/390 • Number of events 1 • Day 1 to up to Day 269; for participants who discontinued early for reasons other than study termination, the timeframe was first dose of study drug to 4 weeks after the last dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.26% 1/390 • Number of events 1 • Day 1 to up to Day 269; for participants who discontinued early for reasons other than study termination, the timeframe was first dose of study drug to 4 weeks after the last dose of study drug.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.26% 1/390 • Number of events 1 • Day 1 to up to Day 269; for participants who discontinued early for reasons other than study termination, the timeframe was first dose of study drug to 4 weeks after the last dose of study drug.
Renal and urinary disorders Nephrolithiasis	0.26% 1/390 • Number of events 1 • Day 1 to up to Day 269; for participants who discontinued early for reasons other than study termination, the timeframe was first dose of study drug to 4 weeks after the last dose of study drug.
Respiratory, thoracic and mediastinal disorders Asthma	0.51% 2/390 • Number of events 2 • Day 1 to up to Day 269; for participants who discontinued early for reasons other than study termination, the timeframe was first dose of study drug to 4 weeks after the last dose of study drug.
Vascular disorders Hypertensive crisis	0.26% 1/390 • Number of events 1 • Day 1 to up to Day 269; for participants who discontinued early for reasons other than study termination, the timeframe was first dose of study drug to 4 weeks after the last dose of study drug.

Other adverse events

Measure	Reslizumab 110 mg n=390 participants at risk Participants were administered reslizumab 110 mg by subcutaneous injection every 4 weeks for a total of 9 doses.
Infections and infestations Upper respiratory tract infection	5.9% 23/390 • Number of events 24 • Day 1 to up to Day 269; for participants who discontinued early for reasons other than study termination, the timeframe was first dose of study drug to 4 weeks after the last dose of study drug.
Infections and infestations Viral upper respiratory tract infection	12.6% 49/390 • Number of events 62 • Day 1 to up to Day 269; for participants who discontinued early for reasons other than study termination, the timeframe was first dose of study drug to 4 weeks after the last dose of study drug.

Additional Information

Director, Clinical Research

Teva Branded Pharmaceutical Products, R&D Inc.

Phone: 1-888-483-8279

Email: USMedInfo@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