Eosinophils, Asthma
Conditions
Brief summary
This is a multicenter, open-label (OL) extension study to obtain additional long-term safety data for subcutaneous (sc) administration of reslizumab treatment administered at a fixed dose of 110 mg in patients 12 years of age and older with severe eosinophilic asthma who completed the treatment period of a placebo-controlled Phase 3 trial of sc reslizumab. The study consists of a screening/baseline visit followed by a 36-week OL treatment period and a 15-week follow-up period.
Interventions
DRUGreslizumab
Reslizumab was provided in a pre-filled syringe.
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
• Patient with eosinophilic asthma who completed the treatment period of a double-blind, placebo controlled sc reslizumab study (Study C38072-AS-30025 or C38072-AS-30027) \ \ Additional criteria apply, please contact the investigator for more information
Exclusion criteria
* Patient has received any reslizumab administration in any previous clinical trial other than Studies C38072-AS-30025 and C38072-AS-30027. * The patient has any clinically significant, uncontrolled medical condition * The patient has another confounding underlying lung disorder * The patient has a known/diagnosed hypereosinophilic syndrome. * The patient has a diagnosis of malignancy within 5 years of the screening visit, except for treated and cured non-melanoma skin cancers. * The patient is a pregnant or lactating woman * The patient is a current smoker (ie, has smoked within the last 6 months before screening) or has a smoking history ≥10 pack-years. * The patient is currently using any systemic immunosuppressive or immunomodulatory agents other than OCS * The patient has a history of allergic reaction or hypersensitivity to any component of the study drug. * The patient has a history of an immunodeficiency disorder including human immunodeficiency virus (HIV). * Additional criteria apply, please contact the investigator for more information
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants With Treatment-Emergent Adverse Events (TEAEs) | 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. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Participants With Potentially Clinically Significant Abnormal Serum Chemistry Values | Week 0 (baseline), Weeks 4, 8, 24, 36 plus any unscheduled visits | 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 |
| Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Weeks 4, 8, 12, 16, 20, 24, 28, and 36 | 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. |
| Participants With Potentially Clinically Significant Abnormal Vital Sign Values | Week 0 (baseline), Weeks 4, 8, 12, 16,20, 24, 28, 32, 36 plus any unscheduled visits | 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 |
| Annualized Rate of Clinical Asthma Exacerbations (CAEs) | 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. | 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. |
| Annualized Rate of Clinical Asthma Exacerbations (CAEs) Requiring Asthma-Specific Hospital Admissions or Emergency Room Visits | 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. | 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. |
| Mean Number of Days of Hospital Stay During the Treatment Period | 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 | Participants with no hospitalizations are included. |
| Mean Number of School/Work Days Missed Due to Asthma During the Treatment Period | 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 | Participants with no school or work days missed due to asthma are included in the counts. |
| Participants With Potentially Clinically Significant Abnormal Hematology Values | Week 0 (baseline), Weeks 8, 24, 36 plus any unscheduled visits | 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 |
| Morning Ambulatory Forced Expiratory Volume in One Second (FEV1): Baseline Values and Change From Baseline Values at Weeks 1, 4, 8, 24 and 36 | Week 0 (baseline), Weeks 1, 4, 8, 24, 36 | 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. |
| Percent Change From Baseline in Daily Oral Corticosteroid (OCS) Dose During Weeks 16-20 and Weeks 32-36 | Week 0 (baseline), Weeks 16-20, Weeks 32-36 | 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) |
| Total Inhalations of Reliever Bronchodilator Medication: Baseline Values and Change From Baseline Values at Weeks 1, 4, 8, 24 and 36 | Baseline (Week 0), Weeks 1, 4, 8, 24, 36 | 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. |
| Asthma Control Questionnaire-6 (ACQ-6) Total Score: Baseline Values and Change From Baseline Values at Weeks 8, 24 and 36 | Baseline (Week 0), Weeks 8, 24, 36 | 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. |
| 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 (Week 0), Weeks 8, 24, 36 | 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. |
| Participants With Treatment-Emergent Anti-Drug Antibody (ADA) Responses | Baseline - date of randomization in the previous study (C38072-AS-30025 or C38072-AS-30027), Weeks 8, 24, 36 or early withdrawal | 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. |
| Participants With Treatment-Emergent Anti-Drug Antibody (ADA) At the End-0f-Study Visit (Week 51) | Week 51 | 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. |
| Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1): Baseline Values and Change From Baseline Values at Weeks 8, 24 and 36 | Week 0 (baseline), Weeks 8, 24, 36 | 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. |
Countries
Belgium, Canada, Czechia, France, Germany, Hungary, Israel, Poland, Romania, Russia, Spain, Ukraine, United States
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 194 |
| 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. | 197 |
| Total | 391 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Pregnancy | 0 | 1 |
| Overall Study | Site closure | 0 | 1 |
| Overall Study | Study terminated by sponsor | 143 | 144 |
| Overall Study | Withdrawal by Subject | 3 | 4 |
Baseline characteristics
| Characteristic | Reslizumab 110 mg; Previous Treatment Placebo | Reslizumab 110 mg: Previous Treatment Reslizumab | Total |
|---|---|---|---|
| Age, Continuous | 50.4 years STANDARD_DEVIATION 14.85 | 52.5 years STANDARD_DEVIATION 15.62 | 51.5 years STANDARD_DEVIATION 15.26 |
| Age, Customized 12 to <18 years | 9 Participants | 8 Participants | 17 Participants |
| Age, Customized 18 to <65 years | 156 Participants | 141 Participants | 297 Participants |
| Age, Customized >=65 years | 29 Participants | 48 Participants | 77 Participants |
| Body Mass Index (BMI) | 28.377 kg/m^2 STANDARD_DEVIATION 5.8288 | 28.880 kg/m^2 STANDARD_DEVIATION 5.9672 | 28.627 kg/m^2 STANDARD_DEVIATION 5.8954 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 18 Participants | 8 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 174 Participants | 187 Participants | 361 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants | 2 Participants | 5 Participants |
| Race/Ethnicity, Customized Black | 7 Participants | 10 Participants | 17 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 182 Participants | 185 Participants | 367 Participants |
| Region Group Europe | 131 Participants | 136 Participants | 267 Participants |
| Region Group Other | 16 Participants | 20 Participants | 36 Participants |
| Region Group U.S./Canada | 47 Participants | 41 Participants | 88 Participants |
| Sex: Female, Male Female | 112 Participants | 122 Participants | 234 Participants |
| Sex: Female, Male Male | 82 Participants | 75 Participants | 157 Participants |
| Systemic Corticosteroid (OCS) Use at Baseline | 12.01 mg prednisolone or equivalent STANDARD_DEVIATION 10.87 | 12.26 mg prednisolone or equivalent STANDARD_DEVIATION 10.76 | 12.14 mg prednisolone or equivalent STANDARD_DEVIATION 10.756 |
| Weight | 79.78 kg STANDARD_DEVIATION 17.647 | 81.22 kg STANDARD_DEVIATION 18.712 | 80.49 kg STANDARD_DEVIATION 18.174 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 390 |
| other Total, other adverse events | 70 / 390 |
| serious Total, serious adverse events | 16 / 390 |
Outcome results
Primary
Participants With Treatment-Emergent Adverse Events (TEAEs)
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.
Time frame: 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
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Reslizumab 110 mg; Previous Treatment Placebo | Participants With Treatment-Emergent Adverse Events (TEAEs) | >=1 TEAE | 102 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants With Treatment-Emergent Adverse Events (TEAEs) | >=1 treatment-related TEAE | 7 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants With Treatment-Emergent Adverse Events (TEAEs) | >=1 serious TEAE | 5 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants With Treatment-Emergent Adverse Events (TEAEs) | >=1 treatment-related, serious TEAE | 0 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants With Treatment-Emergent Adverse Events (TEAEs) | >=1 TEAE leading to discontinuation | 2 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants With Treatment-Emergent Adverse Events (TEAEs) | >=1 TEAE leading to death | 0 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants With Treatment-Emergent Adverse Events (TEAEs) | >=1 TEAE leading to discontinuation | 0 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants With Treatment-Emergent Adverse Events (TEAEs) | >=1 TEAE | 114 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants With Treatment-Emergent Adverse Events (TEAEs) | >=1 treatment-related, serious TEAE | 0 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants With Treatment-Emergent Adverse Events (TEAEs) | >=1 treatment-related TEAE | 6 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants With Treatment-Emergent Adverse Events (TEAEs) | >=1 TEAE leading to death | 0 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants With Treatment-Emergent Adverse Events (TEAEs) | >=1 serious TEAE | 11 Participants |
Secondary
Annualized Rate of Clinical Asthma Exacerbations (CAEs)
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.
Time frame: 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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Reslizumab 110 mg; Previous Treatment Placebo | Annualized Rate of Clinical Asthma Exacerbations (CAEs) | 0.42 CAEs / year | Standard Deviation 1.104 |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Annualized Rate of Clinical Asthma Exacerbations (CAEs) | 0.70 CAEs / year | Standard Deviation 1.538 |
Secondary
Annualized Rate of Clinical Asthma Exacerbations (CAEs) Requiring Asthma-Specific Hospital Admissions or Emergency Room Visits
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.
Time frame: 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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Reslizumab 110 mg; Previous Treatment Placebo | Annualized Rate of Clinical Asthma Exacerbations (CAEs) Requiring Asthma-Specific Hospital Admissions or Emergency Room Visits | 0.06 CAEs / year | Standard Deviation 0.362 |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Annualized Rate of Clinical Asthma Exacerbations (CAEs) Requiring Asthma-Specific Hospital Admissions or Emergency Room Visits | 0.11 CAEs / year | Standard Deviation 0.514 |
Secondary
Asthma Control Questionnaire-6 (ACQ-6) Total Score: Baseline Values and Change From Baseline Values at Weeks 8, 24 and 36
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.
Time frame: Baseline (Week 0), Weeks 8, 24, 36
Population: Safety analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Reslizumab 110 mg; Previous Treatment Placebo | 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 |
| Reslizumab 110 mg; Previous Treatment Placebo | 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 |
| Reslizumab 110 mg; Previous Treatment Placebo | 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 |
| Reslizumab 110 mg; Previous Treatment Placebo | 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 |
| Reslizumab 110 mg; Previous Treatment Reslizumab | 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 | -0.28 units on a scale | Standard Deviation 0.867 |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Asthma Control Questionnaire-6 (ACQ-6) Total Score: Baseline Values and Change From Baseline Values at Weeks 8, 24 and 36 | Baseline - observed values | 1.69 units on a scale | Standard Deviation 1.171 |
| Reslizumab 110 mg; Previous Treatment Reslizumab | 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 | -0.23 units on a scale | Standard Deviation 0.771 |
| Reslizumab 110 mg; Previous Treatment Reslizumab | 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 | -0.20 units on a scale | Standard Deviation 0.718 |
Secondary
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
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.
Time frame: Baseline (Week 0), Weeks 8, 24, 36
Population: Safety Analysis set of participants age 12-70 years
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Reslizumab 110 mg; Previous Treatment Placebo | 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 |
| Reslizumab 110 mg; Previous Treatment Placebo | 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 |
| Reslizumab 110 mg; Previous Treatment Placebo | 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 |
| Reslizumab 110 mg; Previous Treatment Placebo | 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 |
| Reslizumab 110 mg; Previous Treatment Reslizumab | 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 | 0.19 units on a scale | Standard Deviation 0.948 |
| Reslizumab 110 mg; Previous Treatment Reslizumab | 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 | 5.14 units on a scale | Standard Deviation 1.27 |
| Reslizumab 110 mg; Previous Treatment Reslizumab | 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 | 0.20 units on a scale | Standard Deviation 0.83 |
| Reslizumab 110 mg; Previous Treatment Reslizumab | 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 | 0.14 units on a scale | Standard Deviation 0.7 |
Secondary
Mean Number of Days of Hospital Stay During the Treatment Period
Participants with no hospitalizations are included.
Time frame: 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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Reslizumab 110 mg; Previous Treatment Placebo | Mean Number of Days of Hospital Stay During the Treatment Period | 0.25 days | Standard Deviation 1.658 |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Mean Number of Days of Hospital Stay During the Treatment Period | 1.02 days | Standard Deviation 7.848 |
Secondary
Mean Number of School/Work Days Missed Due to Asthma During the Treatment Period
Participants with no school or work days missed due to asthma are included in the counts.
Time frame: 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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Reslizumab 110 mg; Previous Treatment Placebo | Mean Number of School/Work Days Missed Due to Asthma During the Treatment Period | 0.11 days | Standard Deviation 1.202 |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Mean Number of School/Work Days Missed Due to Asthma During the Treatment Period | 0.00 days | Standard Deviation 0 |
Secondary
Morning Ambulatory Forced Expiratory Volume in One Second (FEV1): Baseline Values and Change From Baseline Values at Weeks 1, 4, 8, 24 and 36
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.
Time frame: Week 0 (baseline), Weeks 1, 4, 8, 24, 36
Population: Safety analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Reslizumab 110 mg; Previous Treatment Placebo | 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 |
| Reslizumab 110 mg; Previous Treatment Placebo | 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 |
| Reslizumab 110 mg; Previous Treatment Placebo | 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 0.49 |
| Reslizumab 110 mg; Previous Treatment Placebo | 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 |
| Reslizumab 110 mg; Previous Treatment Placebo | 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 |
| Reslizumab 110 mg; Previous Treatment Placebo | 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 |
| Reslizumab 110 mg; Previous Treatment Reslizumab | 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 | -0.062 liters | Standard Deviation 0.403 |
| Reslizumab 110 mg; Previous Treatment Reslizumab | 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 | 2.027 liters | Standard Deviation 0.847 |
| Reslizumab 110 mg; Previous Treatment Reslizumab | 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 | -0.039 liters | Standard Deviation 0.345 |
| Reslizumab 110 mg; Previous Treatment Reslizumab | 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 | -0.044 liters | Standard Deviation 0.291 |
| Reslizumab 110 mg; Previous Treatment Reslizumab | 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 | -0.053 liters | Standard Deviation 0.465 |
| Reslizumab 110 mg; Previous Treatment Reslizumab | 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 | -0.049 liters | Standard Deviation 0.319 |
Secondary
Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity
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.
Time frame: Weeks 4, 8, 12, 16, 20, 24, 28, and 36
Population: Safety analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Reslizumab 110 mg; Previous Treatment Placebo | Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Pain - Mild | 3 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Pain - Moderate | 0 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Pain - Severe | 0 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Tenderness - None | 193 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Tenderness - Mild | 1 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Tenderness - Moderate | 0 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Tenderness - Severe | 0 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Erythema - None | 191 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Erythema - Mild | 2 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Erythema - Moderate | 1 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Erythema - Severe | 0 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Warmth - None | 192 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Warmth - Mild | 1 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Warmth - Moderate | 1 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Warmth - Severe | 0 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Swelling - None | 191 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Swelling - Mild | 2 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Swelling - Moderate | 1 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Swelling - Severe | 0 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Pain - None | 191 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Warmth - Severe | 0 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Pain - Mild | 2 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Erythema - Severe | 0 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Pain - Moderate | 0 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Swelling - Mild | 5 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Pain - Severe | 0 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Warmth - None | 192 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Tenderness - None | 192 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Pain - None | 194 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Tenderness - Mild | 4 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Swelling - Moderate | 1 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Tenderness - Moderate | 0 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Warmth - Moderate | 0 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Tenderness - Severe | 0 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Warmth - Mild | 4 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Erythema - None | 188 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Swelling - Severe | 0 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Erythema - Mild | 7 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Swelling - None | 190 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants' Tolerability and Injection Site Reactions by Domain and Worst Overall Severity | Erythema - Moderate | 1 Participants |
Secondary
Participants With Potentially Clinically Significant Abnormal Hematology Values
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
Time frame: 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
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Reslizumab 110 mg; Previous Treatment Placebo | Participants With Potentially Clinically Significant Abnormal Hematology Values | Participants with >=1 abnormality | 8 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants With Potentially Clinically Significant Abnormal Hematology Values | Eosinophils (high) | 1 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants With Potentially Clinically Significant Abnormal Hematology Values | Hematocrit (low) | 4 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants With Potentially Clinically Significant Abnormal Hematology Values | Hemoglobin (low) | 2 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants With Potentially Clinically Significant Abnormal Hematology Values | Leukocytes (high) | 0 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants With Potentially Clinically Significant Abnormal Hematology Values | Leukocytes (low) | 2 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants With Potentially Clinically Significant Abnormal Hematology Values | Neutrophils (low) | 1 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants With Potentially Clinically Significant Abnormal Hematology Values | Platelets | 0 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants With Potentially Clinically Significant Abnormal Hematology Values | Platelets | 1 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants With Potentially Clinically Significant Abnormal Hematology Values | Participants with >=1 abnormality | 5 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants With Potentially Clinically Significant Abnormal Hematology Values | Leukocytes (high) | 1 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants With Potentially Clinically Significant Abnormal Hematology Values | Eosinophils (high) | 0 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants With Potentially Clinically Significant Abnormal Hematology Values | Neutrophils (low) | 1 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants With Potentially Clinically Significant Abnormal Hematology Values | Hematocrit (low) | 2 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants With Potentially Clinically Significant Abnormal Hematology Values | Leukocytes (low) | 0 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants With Potentially Clinically Significant Abnormal Hematology Values | Hemoglobin (low) | 0 Participants |
Secondary
Participants With Potentially Clinically Significant Abnormal Serum Chemistry Values
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
Time frame: 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
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Reslizumab 110 mg; Previous Treatment Placebo | Participants With Potentially Clinically Significant Abnormal Serum Chemistry Values | Participants with >=1 abnormality | 12 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants With Potentially Clinically Significant Abnormal Serum Chemistry Values | Alanine Aminotransferase (high) | 1 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants With Potentially Clinically Significant Abnormal Serum Chemistry Values | Aspartate Aminotransferase (high) | 1 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants With Potentially Clinically Significant Abnormal Serum Chemistry Values | Bilirubin (high) | 2 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants With Potentially Clinically Significant Abnormal Serum Chemistry Values | Blood Urea Nitrogen (high) | 2 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants With Potentially Clinically Significant Abnormal Serum Chemistry Values | Creatine Phosphokinase (high) | 2 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants With Potentially Clinically Significant Abnormal Serum Chemistry Values | Creatine Phosphokinase (medium high) | 6 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants With Potentially Clinically Significant Abnormal Serum Chemistry Values | Creatinine (high) | 0 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants With Potentially Clinically Significant Abnormal Serum Chemistry Values | Creatinine (high) | 1 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants With Potentially Clinically Significant Abnormal Serum Chemistry Values | Participants with >=1 abnormality | 10 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants With Potentially Clinically Significant Abnormal Serum Chemistry Values | Blood Urea Nitrogen (high) | 4 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants With Potentially Clinically Significant Abnormal Serum Chemistry Values | Alanine Aminotransferase (high) | 2 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants With Potentially Clinically Significant Abnormal Serum Chemistry Values | Creatine Phosphokinase (medium high) | 4 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants With Potentially Clinically Significant Abnormal Serum Chemistry Values | Aspartate Aminotransferase (high) | 1 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants With Potentially Clinically Significant Abnormal Serum Chemistry Values | Creatine Phosphokinase (high) | 1 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants With Potentially Clinically Significant Abnormal Serum Chemistry Values | Bilirubin (high) | 1 Participants |
Secondary
Participants With Potentially Clinically Significant Abnormal Vital Sign Values
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
Time frame: 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
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Reslizumab 110 mg; Previous Treatment Placebo | Participants With Potentially Clinically Significant Abnormal Vital Sign Values | Pulse Rate - High | 1 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants With Potentially Clinically Significant Abnormal Vital Sign Values | Systolic Blood Pressure - High | 2 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants With Potentially Clinically Significant Abnormal Vital Sign Values | Diastolic Blood Pressure - High | 0 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants With Potentially Clinically Significant Abnormal Vital Sign Values | Temperature - High | 1 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants With Potentially Clinically Significant Abnormal Vital Sign Values | Respiratory Rate - High | 2 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants With Potentially Clinically Significant Abnormal Vital Sign Values | Temperature - Low | 14 Participants |
| Reslizumab 110 mg; Previous Treatment Placebo | Participants With Potentially Clinically Significant Abnormal Vital Sign Values | Participants with >=1 abnormality | 20 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants With Potentially Clinically Significant Abnormal Vital Sign Values | Temperature - Low | 13 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants With Potentially Clinically Significant Abnormal Vital Sign Values | Participants with >=1 abnormality | 16 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants With Potentially Clinically Significant Abnormal Vital Sign Values | Diastolic Blood Pressure - High | 1 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants With Potentially Clinically Significant Abnormal Vital Sign Values | Pulse Rate - High | 2 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants With Potentially Clinically Significant Abnormal Vital Sign Values | Respiratory Rate - High | 0 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants With Potentially Clinically Significant Abnormal Vital Sign Values | Systolic Blood Pressure - High | 0 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants With Potentially Clinically Significant Abnormal Vital Sign Values | Temperature - High | 0 Participants |
Secondary
Participants With Treatment-Emergent Anti-Drug Antibody (ADA) At the End-0f-Study Visit (Week 51)
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.
Time frame: Week 51
Population: Safety Analysis set
Secondary
Participants With Treatment-Emergent Anti-Drug Antibody (ADA) Responses
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.
Time frame: 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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reslizumab 110 mg; Previous Treatment Placebo | Participants With Treatment-Emergent Anti-Drug Antibody (ADA) Responses | 11 Participants |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Participants With Treatment-Emergent Anti-Drug Antibody (ADA) Responses | 9 Participants |
Secondary
Percent Change From Baseline in Daily Oral Corticosteroid (OCS) Dose During Weeks 16-20 and Weeks 32-36
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)
Time frame: Week 0 (baseline), Weeks 16-20, Weeks 32-36
Population: Safety Analysis set of participants on daily OCS at baseline
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Reslizumab 110 mg; Previous Treatment Placebo | 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 |
| Reslizumab 110 mg; Previous Treatment Placebo | 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 |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Percent Change From Baseline in Daily Oral Corticosteroid (OCS) Dose During Weeks 16-20 and Weeks 32-36 | % change at Week 16-20 | -6.96 percent change | Standard Deviation 40.904 |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Percent Change From Baseline in Daily Oral Corticosteroid (OCS) Dose During Weeks 16-20 and Weeks 32-36 | % change at Week 32-36 | -8.75 percent change | Standard Deviation 29.666 |
Secondary
Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1): Baseline Values and Change From Baseline Values at Weeks 8, 24 and 36
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.
Time frame: Week 0 (baseline), Weeks 8, 24, 36
Population: Safety Analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Reslizumab 110 mg; Previous Treatment Placebo | 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 0.98 |
| Reslizumab 110 mg; Previous Treatment Placebo | 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 |
| Reslizumab 110 mg; Previous Treatment Placebo | 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 |
| Reslizumab 110 mg; Previous Treatment Placebo | 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 |
| Reslizumab 110 mg; Previous Treatment Reslizumab | 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 | 0.010 liters | Standard Deviation 0.55 |
| Reslizumab 110 mg; Previous Treatment Reslizumab | 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 | 2.117 liters | Standard Deviation 0.927 |
| Reslizumab 110 mg; Previous Treatment Reslizumab | 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 | -0.020 liters | Standard Deviation 0.472 |
| Reslizumab 110 mg; Previous Treatment Reslizumab | 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 | 0.031 liters | Standard Deviation 0.529 |
Secondary
Total Inhalations of Reliever Bronchodilator Medication: Baseline Values and Change From Baseline Values at Weeks 1, 4, 8, 24 and 36
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.
Time frame: Baseline (Week 0), Weeks 1, 4, 8, 24, 36
Population: Safety Analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Reslizumab 110 mg; Previous Treatment Placebo | 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 |
| Reslizumab 110 mg; Previous Treatment Placebo | 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 1.3 |
| Reslizumab 110 mg; Previous Treatment Placebo | 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 |
| Reslizumab 110 mg; Previous Treatment Placebo | 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 |
| Reslizumab 110 mg; Previous Treatment Placebo | 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 |
| Reslizumab 110 mg; Previous Treatment Placebo | 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 |
| Reslizumab 110 mg; Previous Treatment Reslizumab | 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 1.78 |
| Reslizumab 110 mg; Previous Treatment Reslizumab | Total Inhalations of Reliever Bronchodilator Medication: Baseline Values and Change From Baseline Values at Weeks 1, 4, 8, 24 and 36 | Baseline - observed values | 2.6 inhalations | Standard Deviation 3.1 |
| Reslizumab 110 mg; Previous Treatment Reslizumab | 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 | -0.6 inhalations | Standard Deviation 1.61 |
| Reslizumab 110 mg; Previous Treatment Reslizumab | 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 1.17 |
| Reslizumab 110 mg; Previous Treatment Reslizumab | 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 | -0.6 inhalations | Standard Deviation 1.8 |
| Reslizumab 110 mg; Previous Treatment Reslizumab | 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 | -0.5 inhalations | Standard Deviation 1.5 |