Eosinophilic Asthma
Conditions
Brief summary
The primary objective of this study is to determine whether reslizumab, at a dosage of 0.3 or 3.0 mg/kg administered once every 4 weeks for a total of 4 doses, is more effective than placebo in improving lung function in patients with eosinophilic asthma as assessed by the overall change from baseline in forced expiratory volume in 1 second (FEV1).
Interventions
DRUGReslizumab
3.0 mg/kg or 0.3 mg/kg doses administered intravenously (iv) by qualified site personnel once every 4 weeks, for a total of 4 doses.
DRUGPlacebo
Placebo administered by iv infusion by qualified study personnel every 4 weeks for a total of 4 doses.
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* The patient is male or female, 12 through 75 years of age, with a previous diagnosis of asthma. Patients 12 through 17 years of age are excluded from participating in Argentina. * The patient has an ACQ score of at least 1.5. * The patient has airway reversibility of at least 12% to beta-agonist administration at screening. * The patient is currently taking fluticasone at a dosage of at least 440 μg daily (or equivalent). Patients' baseline asthma therapy regimens (including but not limited to inhaled corticosteroids, leukotriene antagonists, 5-lipoxygenase inhibitors, cromolyn) must be stable for 30 days before screening, and continue without dosage changes throughout study. * The patient has a blood eosinophil count of at least 400/μL. * Female patients must be surgically sterile, 2 years postmenopausal, or must have a negative pregnancy test ßHCG at screening (serum) and baseline (urine). * Female patients of childbearing potential (not surgically sterile or 2 years postmenopausal), must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study and for 30 days after the end-of-treatment visit. Acceptable methods of contraception include barrier method with spermicide, abstinence, intrauterine device (IUD), or steroidal contraceptive (oral, transdermal, implanted, and injected). * Written informed consent is obtained. Patients 12 through 17 years old, where participating, need to provide assent in accordance with local standards. * Other inclusion criteria apply.
Exclusion criteria
* The patient has a clinically meaningful comorbidity that would interfere with the study schedule or procedures, or compromise the patient's safety. * The patient has known hypereosinophilic syndrome (HES). * The patient has another confounding underlying lung disorder (eg, chronic obstructive pulmonary disease, pulmonary fibrosis, or lung cancer). The patient has other pulmonary conditions with symptoms of asthma and blood eosinophilia (eg, Churg-Strauss syndrome, allergic bronchopulmonary aspergillosis). * The patient is a current smoker (ie, has smoked within the last 6 months prior to screening). * The patient has a history of use of systemic immunosuppressive or immunomodulating agents (anti-IgE mAb, methotrexate, cyclosporin, interferon-α, or anti-tumor necrosis factor mAb) within 6 months prior to study entry (screening). * The patient is currently using systemic corticosteroids (includes use of oral corticosteroids). * The patient has a current infection or disease that may preclude assessment of asthma. * The patient is expected to be poorly compliant with study drug administration, study procedures, or visits. * The patient has any aggravating factors that are inadequately controlled (eg, gastroesophageal reflux disease). * The patient has participated in any investigative drug or device study within 30 days prior to screening. * The patient has participated in any investigative biologics study within 90 days prior to screening. * The patient has previously received anti-hIL-5 monoclonal antibody (eg, mepolizumab). * Female patients who are pregnant, or nursing, or, if of childbearing potential and not using a medically accepted, effective method of birth control (e.g. spermicide, abstinence, IUD, or steroidal contraceptive \[oral, transdermal, implanted, and injected\]) are excluded from this study. * The patient has a current infection or disease that may preclude assessment of asthma. * The patient has a history of concurrent immunodeficiency (human immunodeficiency, acquired immunodeficiency syndrome, or congenital immunodeficiency). Patients in Argentina must have documented serology testing for HIV performed during screening. * Other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline In Forced Expiratory Volume In 1 Second (FEV1) Over 16 Weeks Using Mixed Model for Repeated Measures | Day 0 (baseline, pre-dose), Weeks 4, 8, 12 and 16 | FEV1 is a standard measurement of air movement in the lungs of patients with asthma obtained from pulmonary function tests. It is the volume of air expired in the first second of a forced expiration using a spirometer. The during treatment (weeks 4, 8, 12 and 16) average FEV1 was estimated using a mixed-effect model for repeated measures (MMRM) with fixed effects (treatment, stratification factors, sex, visit, interaction of treatment and visit), covariates (height, baseline value), and patient as the random effect for the repeated measurements. Positive change from baseline scores indicate improvement in asthma control. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Forced Expiratory Flow at 25% to 75% Forced Vital Capacity (FEF 25%-75%) Over 16 Weeks Using Mixed Model for Repeated Measures | Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16 | The FEF 25%-75% is the force expiratory flow at 25% to 75% of the Forced Vital Capacity (FVC). The during treatment (weeks 4, 8, 12 and 16) average FEF 25%-75% was estimated using a mixed-effect model for repeated measures (MMRM) with fixed effects (treatment, stratification factors, sex, visit, interaction of treatment and visit), covariates (height, baseline value), and patient as the random effect for the repeated measurements. |
| Change From Baseline in % Predicted Expiratory Volume In 1 Second (FEV1) at Week 16 and at Endpoint | Day 1 (baseline, pre-dose), Week 16, endpoint | The percent predicted FEV1 is the ratio of the volume of air expired in the first second of a forced expiration to the patient's predicted FEV based on a similar population without asthma. Endpoint =week 16 or early withdrawal. |
| Change From Baseline in Asthma Control Questionnaire (ACQ) Over 16 Weeks Using Mixed Model for Repeated Measures | Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16 | The ACQ is a 7-item instrument that measures asthma control (Juniper et al 1999). Six questions are self-assessments; the seventh item, completed by a member of the study staff, is the result of the patient's FEV1 measurement. Each item has 7 possible answers on a scale of 0 to 6, and the total score is the mean of all responses (the total scale is therefore 0-6). A higher score is an indication of poorer asthma control. The during treatment (weeks 4, 8, 12 and 16) average ACQ was estimated using a mixed-effect model for repeated measures (MMRM) with fixed effects (treatment, stratification factors, sex, visit, interaction of treatment and visit), covariates (height, baseline value), and patient as the random effect for the repeated measurements. Negative change from baseline scores indicate improvement in asthma control. |
| Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) at Week 16 or at Last Observed Value | Day 1 (baseline, pre-dose), Week 16 or last observed value | The AQLQ is a 32-item instrument administered as a self-assessment (Juniper et al 1992). The questionnaire is divided into 4 domains: activity limitation, symptoms, emotional function, and environmental stimuli. Patients were asked to recall their experiences during the last 2 weeks and to respond to each question on a 7-point scale (1=severe impairment, 7=no impairment). The overall AQLQ score is the mean of all 32 responses. Five of the activity questions were patient-specific, which means that each patient identified and scored 5 activities in which the patient was limited by asthma; these 5 activities were identified at the first visit and retained for all subsequent follow-up visits. Positive change from baseline scores indicate improvement in quality of life. The AQLQ score was only assessed once during the study at week 16 or at early withdrawal, i.e. last postbaseline assessment if within 3 to 5 weeks of the last dose of study drug. |
| Change From Baseline in Asthma Symptom Utility Index (ASUI) Over 16 Weeks Using Mixed Model for Repeated Measures | Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16 | The ASUI is an 11-item instrument designed to assess the frequency and severity of asthma symptoms and side effects, weighted by patient preferences (Revicki et al 1998). ASUI is a utility score that ranges from 0 to 1, with higher values indicating better asthma control. The during treatment (weeks 4, 8, 12 and 16) average ASUI was estimated using a mixed-effect model for repeated measures (MMRM) with fixed effects (treatment, stratification factors, sex, visit, interaction of treatment and visit), covariates (height, baseline value), and patient as the random effect for the repeated measurements. Positive change from baseline values indicate improvement in asthma symptoms. Information was obtained from questionnaire about asthma symptoms. |
| Change From Baseline in Short-Acting Beta-Agonist (SABA) Use Over 16 Weeks Using Mixed Model for Repeated Measures | Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16 | SABA are used for quick relief of asthma symptoms. To measure SABA use, at each clinical visit patients were asked to recall their usage of SABA therapy within the last 3 days of the scheduled visit. If usage was confirmed, the number of puffs used was recorded. For the purpose of summaries, an average daily usage was evaluated by dividing the total number of puffs recorded over 3 days by 3. The during treatment (weeks 4, 8, 12 and 16) average SABA use was estimated using a mixed-effect model for repeated measures (MMRM) with fixed effects (treatment, stratification factors, sex, visit, interaction of treatment and visit), covariates (height, baseline value), and patient as the random effect for the repeated measurements. Negative change from baseline scores indicate improvement in asthma control. |
| Change From Baseline in Forced Vital Capacity (FVC) Over 16 Weeks Using Mixed Model for Repeated Measures | Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16 | The FVC is the volume of air that can be forcibly blown out after full inspiration, measured in liters. The during treatment (weeks 4, 8, 12 and 16) average FVC was estimated using a mixed-effect model for repeated measures (MMRM) with fixed effects (treatment, stratification factors, sex, visit, interaction of treatment and visit), covariates (height, baseline value), and patient as the random effect for the repeated measurements. |
| Participants With Adverse Events | Day 1 (post-dose) to Week 29 | An adverse event was defined in the protocol as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an inability to carry out usual activities. Relation of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes. The last postbaseline value for approximately 10 patients in each treatment group is the 90-day follow-up visit post end-of-treatment (approx. Week 29). |
| Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Day 2 to Week 29 | Data represents participants with potentially clinically significant (PCS) abnormal serum chemistry, hematology (except for eosinophil values), and urinalysis values. Significance criteria: * Blood urea nitrogen: \>=10.71 mmol/L * Creatinine: \>=177 μmol/L * Uric acid: M\>=625, F\>=506 μmol/L * GGT = gamma-glutamyl transpeptidase: \>= 3\*upper limit of normal. Normal range is 5-49 U/L. * Total bilirubin: \>=34.2 μmol/L * White blood cells: \<=3.0 10\^9/L * Hemoglobin: M\<=115, F\<=95 g/dL * Hematocrit: M\<0.37, F\<0.32 % * Platelets: \>=700 10\^9/L * Absolute neutrophil count: \<=1.0 10\^9/L * Urinalysis: blood, glucose, ketones and total protein: \>=2 unit increase from baseline The last postbaseline value for approximately 10 patients in each treatment group is the 90-day follow-up visit post end-of-treatment (approx. Week 29). |
| Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Day 2 to Week 29 | Data represents participants with potentially clinically significant (PCS) vital sign values. Significance criteria * Sitting pulse - high: \>100 and increase of \>= 30 beats/minute * Sitting pulse - low: \<50 and decrease of \>=30 beats/minute * Sitting diastolic blood pressure: \>100 and increase of \>=12 mmHg * Respiration rate: \>24 and increase of \>=10 breaths/minute * Body temperature: \<96.5° Fahrenheit or \<35.8° Celsius The last postbaseline value for approximately 10 patients in each treatment group is the 90-day follow-up visit post end-of-treatment (approx. Week 29). |
| Shifts From Baseline to Endpoint in Electrocardiogram Findings | Weeks -4 to -2 (Screening Visit), Week 16 | Participant counts in each category of shift from baseline to endpoint of ECG finding. Findings summarized as normal or abnormal. |
| Participants With a Positive Anti-Reslizumab Antibody Status at Baseline, Week 8, Week 16, Endpoint, and Overall | Day 1 (pre-dose), week 8, 16 and endpoint | Counts of participants with a positive anti-drug antibody (ADA) response during treatment is offered for the two experimental treatment arms. Blood samples were collected for determination of ADAs before study drug infusion at baseline, visit 4 (week 8), and at visit 6 (week 16: EOT or early withdrawal) from patients in all 3 treatment groups (ie, placebo, 0.3 mg/kg reslizumab, and 3.0 mg/kg reslizumab); however, only the blood samples drawn from patients treated with either 0.3 mg/kg reslizumab or 3.0 mg/kg reslizumab were analyzed. Serum samples from patients who were treated with reslizumab were analyzed for ADA by Teva (Teva Biopharmaceuticals USA, Rockville, MD) using a validated homogeneous solution-based bridging enzyme-linked immunosorbent assay (ELISA). Endpoint =week 16 or early withdrawal. |
| Change From Baseline in Blood Eosinophil Count Over 16 Weeks Using Mixed Model for Repeated Measures | Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16 | Blood eosinophil counts were measured using a standard complete blood count (CBC) with differential blood test at each scheduled visit, and from all patients experiencing a serious adverse event, an adverse event leading to withdrawal, or an exacerbation of asthma symptoms. The during treatment (weeks 4, 8, 12 and 16) average eosinophil counts were estimated using a mixed-effect model for repeated measures (MMRM) with fixed effects (treatment, stratification factors, sex, visit, interaction of treatment and visit), covariates (height, baseline value), and patient as the random effect for the repeated measurements. Negative change from baseline values correlate to reduced asthma severity. |
Countries
Argentina, Belgium, Brazil, Canada, Colombia, France, Hungary, Israel, Mexico, Netherlands, Poland, Sweden, United States
Participant flow
Pre-assignment details
Of the 1025 patients screened at 80 centers in 12 countries (Argentina, Belgium, Brazil, Canada, Colombia, Hungary, Israel, Mexico, Netherlands, Poland, Sweden, and the US), 315 patients met entry criteria at 68 centers and were considered to be eligible for enrollment.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo administered intravenously (iv) once every 4 weeks, for a total of 4 doses. | 105 |
| Reslizumab - 0.3 mg/kg 0.3 mg/kg, administered intravenously (iv) once every 4 weeks, for a total of 4 doses | 104 |
| Reslizumab - 3.0 mg/kg 3.0 mg/kg, administered intravenously (iv) once every 4 weeks, for a total of 4 doses. | 106 |
| Total | 315 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 9 | 1 | 7 |
| Overall Study | Lack of Efficacy | 2 | 3 | 1 |
| Overall Study | Lost to Follow-up | 2 | 3 | 1 |
| Overall Study | Other | 1 | 1 | 3 |
| Overall Study | Protocol Violation | 4 | 3 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 1 | 4 |
Baseline characteristics
| Characteristic | Reslizumab - 3.0 mg/kg | Reslizumab - 0.3 mg/kg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 43.0 years STANDARD_DEVIATION 14.41 | 44.5 years STANDARD_DEVIATION 14.03 | 44.2 years STANDARD_DEVIATION 14.89 | 43.9 years STANDARD_DEVIATION 14.42 |
| Age, Customized Adolescents (12-17 years) | 5 participants | 5 participants | 5 participants | 15 participants |
| Age, Customized Adults (18-64 years) | 99 participants | 91 participants | 93 participants | 283 participants |
| Age, Customized From 65-84 years | 2 participants | 8 participants | 7 participants | 17 participants |
| Asthma Exacerbation Within the Last 12 Months No | 46 participants | 46 participants | 48 participants | 140 participants |
| Asthma Exacerbation Within the Last 12 Months Yes | 60 participants | 58 participants | 57 participants | 175 participants |
| Body Mass Index | 27.4 kg/m^2 STANDARD_DEVIATION 6.87 | 27.6 kg/m^2 STANDARD_DEVIATION 6.68 | 27.7 kg/m^2 STANDARD_DEVIATION 6.01 | 27.6 kg/m^2 STANDARD_DEVIATION 6.51 |
| Height | 165.9 cm STANDARD_DEVIATION 10.24 | 166.2 cm STANDARD_DEVIATION 12.21 | 166.4 cm STANDARD_DEVIATION 10.93 | 166.2 cm STANDARD_DEVIATION 11.12 |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 0 participants | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Asian | 2 participants | 2 participants | 0 participants | 4 participants |
| Race/Ethnicity, Customized Black | 5 participants | 6 participants | 7 participants | 18 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 31 participants | 29 participants | 29 participants | 89 participants |
| Race/Ethnicity, Customized Non-Hispanic and Non-Latino | 75 participants | 73 participants | 74 participants | 222 participants |
| Race/Ethnicity, Customized Other | 9 participants | 16 participants | 11 participants | 36 participants |
| Race/Ethnicity, Customized Pacific Islander | 0 participants | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Unknown | 0 participants | 2 participants | 2 participants | 4 participants |
| Race/Ethnicity, Customized White | 90 participants | 80 participants | 85 participants | 255 participants |
| Sex: Female, Male Female | 62 Participants | 59 Participants | 62 Participants | 183 Participants |
| Sex: Female, Male Male | 44 Participants | 45 Participants | 43 Participants | 132 Participants |
| Weight | 75.7 kg STANDARD_DEVIATION 20.3 | 75.9 kg STANDARD_DEVIATION 18.8 | 77.0 kg STANDARD_DEVIATION 20.1 | 76.2 kg STANDARD_DEVIATION 19.7 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 28 / 105 | 20 / 103 | 28 / 103 |
| serious Total, serious adverse events | 1 / 105 | 0 / 103 | 4 / 103 |
Outcome results
Primary
Change From Baseline In Forced Expiratory Volume In 1 Second (FEV1) Over 16 Weeks Using Mixed Model for Repeated Measures
FEV1 is a standard measurement of air movement in the lungs of patients with asthma obtained from pulmonary function tests. It is the volume of air expired in the first second of a forced expiration using a spirometer. The during treatment (weeks 4, 8, 12 and 16) average FEV1 was estimated using a mixed-effect model for repeated measures (MMRM) with fixed effects (treatment, stratification factors, sex, visit, interaction of treatment and visit), covariates (height, baseline value), and patient as the random effect for the repeated measurements. Positive change from baseline scores indicate improvement in asthma control.
Time frame: Day 0 (baseline, pre-dose), Weeks 4, 8, 12 and 16
Population: Full analysis set-all patients randomly assigned to treatment and treated with at least 1 dose of study drug. Number of participants analyzed includes those who contributed at least once to the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline In Forced Expiratory Volume In 1 Second (FEV1) Over 16 Weeks Using Mixed Model for Repeated Measures | 0.126 liters | Standard Error 0.0549 |
| Reslizumab - 0.3 mg/kg | Change From Baseline In Forced Expiratory Volume In 1 Second (FEV1) Over 16 Weeks Using Mixed Model for Repeated Measures | 0.242 liters | Standard Error 0.0556 |
| Reslizumab - 3.0 mg/kg | Change From Baseline In Forced Expiratory Volume In 1 Second (FEV1) Over 16 Weeks Using Mixed Model for Repeated Measures | 0.286 liters | Standard Error 0.0548 |
Comparison: The primary variable was analyzed using a mixed-effect model for repeated measures (MMRM) with fixed effects (treatment, stratification factors, sex, visit, interaction of treatment and visit), covariates (height, baseline value), and patient as the random effect for the repeated measurements.p-value: 0.001895% CI: [0.06, 0.259]Mixed Models Analysis
Comparison: The primary variable was analyzed using a mixed-effect model for repeated measures (MMRM) with fixed effects (treatment, stratification factors, sex, visit, interaction of treatment and visit), covariates (height, baseline value), and patient as the random effect for the repeated measurements.p-value: 0.023795% CI: [0.016, 0.215]Mixed Models Analysis
Secondary
Change From Baseline in Asthma Control Questionnaire (ACQ) Over 16 Weeks Using Mixed Model for Repeated Measures
The ACQ is a 7-item instrument that measures asthma control (Juniper et al 1999). Six questions are self-assessments; the seventh item, completed by a member of the study staff, is the result of the patient's FEV1 measurement. Each item has 7 possible answers on a scale of 0 to 6, and the total score is the mean of all responses (the total scale is therefore 0-6). A higher score is an indication of poorer asthma control. The during treatment (weeks 4, 8, 12 and 16) average ACQ was estimated using a mixed-effect model for repeated measures (MMRM) with fixed effects (treatment, stratification factors, sex, visit, interaction of treatment and visit), covariates (height, baseline value), and patient as the random effect for the repeated measurements. Negative change from baseline scores indicate improvement in asthma control.
Time frame: Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16
Population: Full analysis set, including participants who contributed at least once to the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Asthma Control Questionnaire (ACQ) Over 16 Weeks Using Mixed Model for Repeated Measures | -0.494 units on a scale | Standard Error 0.1231 |
| Reslizumab - 0.3 mg/kg | Change From Baseline in Asthma Control Questionnaire (ACQ) Over 16 Weeks Using Mixed Model for Repeated Measures | -0.732 units on a scale | Standard Error 0.125 |
| Reslizumab - 3.0 mg/kg | Change From Baseline in Asthma Control Questionnaire (ACQ) Over 16 Weeks Using Mixed Model for Repeated Measures | -0.853 units on a scale | Standard Error 0.1233 |
Comparison: As with the primary outcome, this respiratory test outcome was analyzed using a mixed-effect model for repeated measures (MMRM) with fixed effects (treatment, stratification factors, sex, visit, interaction of treatment and visit), covariates (height, baseline value), and patient as the random effect for the repeated measurements.p-value: 0.001495% CI: [-0.577, -0.14]Mixed Models Analysis
Comparison: As with the primary outcome, this respiratory test outcome was analyzed using a mixed-effect model for repeated measures (MMRM) with fixed effects (treatment, stratification factors, sex, visit, interaction of treatment and visit), covariates (height, baseline value), and patient as the random effect for the repeated measurements.p-value: 0.032995% CI: [-0.456, -0.019]Mixed Models Analysis
Secondary
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) at Week 16 or at Last Observed Value
The AQLQ is a 32-item instrument administered as a self-assessment (Juniper et al 1992). The questionnaire is divided into 4 domains: activity limitation, symptoms, emotional function, and environmental stimuli. Patients were asked to recall their experiences during the last 2 weeks and to respond to each question on a 7-point scale (1=severe impairment, 7=no impairment). The overall AQLQ score is the mean of all 32 responses. Five of the activity questions were patient-specific, which means that each patient identified and scored 5 activities in which the patient was limited by asthma; these 5 activities were identified at the first visit and retained for all subsequent follow-up visits. Positive change from baseline scores indicate improvement in quality of life. The AQLQ score was only assessed once during the study at week 16 or at early withdrawal, i.e. last postbaseline assessment if within 3 to 5 weeks of the last dose of study drug.
Time frame: Day 1 (baseline, pre-dose), Week 16 or last observed value
Population: Full analysis set of participants with assessments at stated timeframes.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) at Week 16 or at Last Observed Value | 0.779 units on a scale | Standard Error 0.1817 |
| Reslizumab - 0.3 mg/kg | Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) at Week 16 or at Last Observed Value | 1.057 units on a scale | Standard Error 0.1881 |
| Reslizumab - 3.0 mg/kg | Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) at Week 16 or at Last Observed Value | 1.138 units on a scale | Standard Error 0.1829 |
Comparison: As with the primary outcome, this respiratory test outcome was analyzed using a mixed-effect model for repeated measures (MMRM) with fixed effects (treatment, stratification factors, sex, visit, interaction of treatment and visit), covariates (height, baseline value), and patient as the random effect for the repeated measurements.p-value: 0.024195% CI: [0.047, 0.67]Mixed Models Analysis
Comparison: As with the primary outcome, this respiratory test outcome was analyzed using a mixed-effect model for repeated measures (MMRM) with fixed effects (treatment, stratification factors, sex, visit, interaction of treatment and visit), covariates (height, baseline value), and patient as the random effect for the repeated measurements.p-value: 0.082295% CI: [-0.036, 0.591]Mixed Models Analysis
Secondary
Change From Baseline in Asthma Symptom Utility Index (ASUI) Over 16 Weeks Using Mixed Model for Repeated Measures
The ASUI is an 11-item instrument designed to assess the frequency and severity of asthma symptoms and side effects, weighted by patient preferences (Revicki et al 1998). ASUI is a utility score that ranges from 0 to 1, with higher values indicating better asthma control. The during treatment (weeks 4, 8, 12 and 16) average ASUI was estimated using a mixed-effect model for repeated measures (MMRM) with fixed effects (treatment, stratification factors, sex, visit, interaction of treatment and visit), covariates (height, baseline value), and patient as the random effect for the repeated measurements. Positive change from baseline values indicate improvement in asthma symptoms. Information was obtained from questionnaire about asthma symptoms.
Time frame: Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16
Population: Full analysis set, including patients who contributed at least once to the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Asthma Symptom Utility Index (ASUI) Over 16 Weeks Using Mixed Model for Repeated Measures | 0.082 units on a scale | Standard Error 0.0218 |
| Reslizumab - 0.3 mg/kg | Change From Baseline in Asthma Symptom Utility Index (ASUI) Over 16 Weeks Using Mixed Model for Repeated Measures | 0.132 units on a scale | Standard Error 0.0221 |
| Reslizumab - 3.0 mg/kg | Change From Baseline in Asthma Symptom Utility Index (ASUI) Over 16 Weeks Using Mixed Model for Repeated Measures | 0.129 units on a scale | Standard Error 0.0218 |
Comparison: As with the primary outcome, this respiratory test outcome was analyzed using a mixed-effect model for repeated measures (MMRM) with fixed effects (treatment, stratification factors, sex, visit, interaction of treatment and visit), covariates (height, baseline value), and patient as the random effect for the repeated measurements.p-value: 0.01695% CI: [0.009, 0.085]Mixed Models Analysis
Comparison: As with the primary outcome, this respiratory test outcome was analyzed using a mixed-effect model for repeated measures (MMRM) with fixed effects (treatment, stratification factors, sex, visit, interaction of treatment and visit), covariates (height, baseline value), and patient as the random effect for the repeated measurements.p-value: 0.009495% CI: [0.012, 0.089]Mixed Models Analysis
Secondary
Change From Baseline in Blood Eosinophil Count Over 16 Weeks Using Mixed Model for Repeated Measures
Blood eosinophil counts were measured using a standard complete blood count (CBC) with differential blood test at each scheduled visit, and from all patients experiencing a serious adverse event, an adverse event leading to withdrawal, or an exacerbation of asthma symptoms. The during treatment (weeks 4, 8, 12 and 16) average eosinophil counts were estimated using a mixed-effect model for repeated measures (MMRM) with fixed effects (treatment, stratification factors, sex, visit, interaction of treatment and visit), covariates (height, baseline value), and patient as the random effect for the repeated measurements. Negative change from baseline values correlate to reduced asthma severity.
Time frame: Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16
Population: Full analysis set, including patients who contributed at least once to the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Blood Eosinophil Count Over 16 Weeks Using Mixed Model for Repeated Measures | -0.035 10^9 blood eosinophil/L | Standard Error 0.0271 |
| Reslizumab - 0.3 mg/kg | Change From Baseline in Blood Eosinophil Count Over 16 Weeks Using Mixed Model for Repeated Measures | -0.358 10^9 blood eosinophil/L | Standard Error 0.0277 |
| Reslizumab - 3.0 mg/kg | Change From Baseline in Blood Eosinophil Count Over 16 Weeks Using Mixed Model for Repeated Measures | -0.529 10^9 blood eosinophil/L | Standard Error 0.027 |
Comparison: As with the primary outcome, this respiratory test outcome was analyzed using a mixed-effect model for repeated measures (MMRM) with fixed effects (treatment, stratification factors, sex, visit, interaction of treatment and visit), covariates (height, baseline value), and patient as the random effect for the repeated measurements.p-value: 095% CI: [-0.542, -0.447]Regression, Logistic
Comparison: As with the primary outcome, this respiratory test outcome was analyzed using a mixed-effect model for repeated measures (MMRM) with fixed effects (treatment, stratification factors, sex, visit, interaction of treatment and visit), covariates (height, baseline value), and patient as the random effect for the repeated measurements.p-value: 095% CI: [-0.37, -0.275]Mixed Models Analysis
Secondary
Change From Baseline in Forced Expiratory Flow at 25% to 75% Forced Vital Capacity (FEF 25%-75%) Over 16 Weeks Using Mixed Model for Repeated Measures
The FEF 25%-75% is the force expiratory flow at 25% to 75% of the Forced Vital Capacity (FVC). The during treatment (weeks 4, 8, 12 and 16) average FEF 25%-75% was estimated using a mixed-effect model for repeated measures (MMRM) with fixed effects (treatment, stratification factors, sex, visit, interaction of treatment and visit), covariates (height, baseline value), and patient as the random effect for the repeated measurements.
Time frame: Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16
Population: Full analysis set. Number of participants analyzed includes those who contributed at least once to the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Forced Expiratory Flow at 25% to 75% Forced Vital Capacity (FEF 25%-75%) Over 16 Weeks Using Mixed Model for Repeated Measures | -0.145 liters/second | Standard Error 0.1342 |
| Reslizumab - 0.3 mg/kg | Change From Baseline in Forced Expiratory Flow at 25% to 75% Forced Vital Capacity (FEF 25%-75%) Over 16 Weeks Using Mixed Model for Repeated Measures | -0.114 liters/second | Standard Error 0.1361 |
| Reslizumab - 3.0 mg/kg | Change From Baseline in Forced Expiratory Flow at 25% to 75% Forced Vital Capacity (FEF 25%-75%) Over 16 Weeks Using Mixed Model for Repeated Measures | 0.089 liters/second | Standard Error 0.1342 |
Comparison: As with the primary outcome, this respiratory test outcome was analyzed using a mixed-effect model for repeated measures (MMRM) with fixed effects (treatment, stratification factors, sex, visit, interaction of treatment and visit), covariates (height, baseline value), and patient as the random effect for the repeated measurements.p-value: 0.055295% CI: [-0.005, 0.472]Mixed Models Analysis
Comparison: As with the primary outcome, this respiratory test outcome was analyzed using a mixed-effect model for repeated measures (MMRM) with fixed effects (treatment, stratification factors, sex, visit, interaction of treatment and visit), covariates (height, baseline value), and patient as the random effect for the repeated measurements.p-value: 0.80295% CI: [-0.209, 0.27]Mixed Models Analysis
Secondary
Change From Baseline in Forced Vital Capacity (FVC) Over 16 Weeks Using Mixed Model for Repeated Measures
The FVC is the volume of air that can be forcibly blown out after full inspiration, measured in liters. The during treatment (weeks 4, 8, 12 and 16) average FVC was estimated using a mixed-effect model for repeated measures (MMRM) with fixed effects (treatment, stratification factors, sex, visit, interaction of treatment and visit), covariates (height, baseline value), and patient as the random effect for the repeated measurements.
Time frame: Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16
Population: Full analysis set. Number of participants analyzed includes those who contributed at least once to the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) Over 16 Weeks Using Mixed Model for Repeated Measures | 0.172 liters | Standard Error 0.0614 |
| Reslizumab - 0.3 mg/kg | Change From Baseline in Forced Vital Capacity (FVC) Over 16 Weeks Using Mixed Model for Repeated Measures | 0.220 liters | Standard Error 0.0623 |
| Reslizumab - 3.0 mg/kg | Change From Baseline in Forced Vital Capacity (FVC) Over 16 Weeks Using Mixed Model for Repeated Measures | 0.301 liters | Standard Error 0.0613 |
Comparison: As with the primary outcome, this respiratory test outcome was analyzed using a mixed-effect model for repeated measures (MMRM) with fixed effects (treatment, stratification factors, sex, visit, interaction of treatment and visit), covariates (height, baseline value), and patient as the random effect for the repeated measurements.p-value: 0.017495% CI: [0.023, 0.237]Mixed Models Analysis
Comparison: As with the primary outcome, this respiratory test outcome was analyzed using a mixed-effect model for repeated measures (MMRM) with fixed effects (treatment, stratification factors, sex, visit, interaction of treatment and visit), covariates (height, baseline value), and patient as the random effect for the repeated measurements.p-value: 0.373195% CI: [-0.058, 0.155]Mixed Models Analysis
Secondary
Change From Baseline in % Predicted Expiratory Volume In 1 Second (FEV1) at Week 16 and at Endpoint
The percent predicted FEV1 is the ratio of the volume of air expired in the first second of a forced expiration to the patient's predicted FEV based on a similar population without asthma. Endpoint =week 16 or early withdrawal.
Time frame: Day 1 (baseline, pre-dose), Week 16, endpoint
Population: Full analysis set of participants with assessments at stated timeframes.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in % Predicted Expiratory Volume In 1 Second (FEV1) at Week 16 and at Endpoint | Week 16 (n=84, 92, 91) | 0.8 percentage of predicted FEV1 | Standard Deviation 11.92 |
| Placebo | Change From Baseline in % Predicted Expiratory Volume In 1 Second (FEV1) at Week 16 and at Endpoint | Endpoint (n=103, 101, 102) | 0.8 percentage of predicted FEV1 | Standard Deviation 13.83 |
| Reslizumab - 0.3 mg/kg | Change From Baseline in % Predicted Expiratory Volume In 1 Second (FEV1) at Week 16 and at Endpoint | Week 16 (n=84, 92, 91) | 4.9 percentage of predicted FEV1 | Standard Deviation 15.06 |
| Reslizumab - 0.3 mg/kg | Change From Baseline in % Predicted Expiratory Volume In 1 Second (FEV1) at Week 16 and at Endpoint | Endpoint (n=103, 101, 102) | 5.5 percentage of predicted FEV1 | Standard Deviation 15.16 |
| Reslizumab - 3.0 mg/kg | Change From Baseline in % Predicted Expiratory Volume In 1 Second (FEV1) at Week 16 and at Endpoint | Week 16 (n=84, 92, 91) | 7.5 percentage of predicted FEV1 | Standard Deviation 14.74 |
| Reslizumab - 3.0 mg/kg | Change From Baseline in % Predicted Expiratory Volume In 1 Second (FEV1) at Week 16 and at Endpoint | Endpoint (n=103, 101, 102) | 6.7 percentage of predicted FEV1 | Standard Deviation 15.01 |
Secondary
Change From Baseline in Short-Acting Beta-Agonist (SABA) Use Over 16 Weeks Using Mixed Model for Repeated Measures
SABA are used for quick relief of asthma symptoms. To measure SABA use, at each clinical visit patients were asked to recall their usage of SABA therapy within the last 3 days of the scheduled visit. If usage was confirmed, the number of puffs used was recorded. For the purpose of summaries, an average daily usage was evaluated by dividing the total number of puffs recorded over 3 days by 3. The during treatment (weeks 4, 8, 12 and 16) average SABA use was estimated using a mixed-effect model for repeated measures (MMRM) with fixed effects (treatment, stratification factors, sex, visit, interaction of treatment and visit), covariates (height, baseline value), and patient as the random effect for the repeated measurements. Negative change from baseline scores indicate improvement in asthma control.
Time frame: Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16
Population: Full analysis set, including patients who contributed at least once to the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Short-Acting Beta-Agonist (SABA) Use Over 16 Weeks Using Mixed Model for Repeated Measures | -0.3 SABA puffs per day | Standard Error 0.28 |
| Reslizumab - 0.3 mg/kg | Change From Baseline in Short-Acting Beta-Agonist (SABA) Use Over 16 Weeks Using Mixed Model for Repeated Measures | -1.0 SABA puffs per day | Standard Error 0.28 |
| Reslizumab - 3.0 mg/kg | Change From Baseline in Short-Acting Beta-Agonist (SABA) Use Over 16 Weeks Using Mixed Model for Repeated Measures | -0.9 SABA puffs per day | Standard Error 0.27 |
Comparison: As with the primary outcome, this respiratory test outcome was analyzed using a mixed-effect model for repeated measures (MMRM) with fixed effects (treatment, stratification factors, sex, visit, interaction of treatment and visit), covariates (height, baseline value), and patient as the random effect for the repeated measurements.p-value: 0.015195% CI: [-1.126, -0.121]Mixed Models Analysis
Comparison: As with the primary outcome, this respiratory test outcome was analyzed using a mixed-effect model for repeated measures (MMRM) with fixed effects (treatment, stratification factors, sex, visit, interaction of treatment and visit), covariates (height, baseline value), and patient as the random effect for the repeated measurements.p-value: 0.011995% CI: [-1.152, -0.144]Mixed Models Analysis
Secondary
Participants With Adverse Events
An adverse event was defined in the protocol as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an inability to carry out usual activities. Relation of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes. The last postbaseline value for approximately 10 patients in each treatment group is the 90-day follow-up visit post end-of-treatment (approx. Week 29).
Time frame: Day 1 (post-dose) to Week 29
Population: Safety analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Participants With Adverse Events | Treatment-related AE | 8 participants |
| Placebo | Participants With Adverse Events | Withdrawn from study due to AE | 10 participants |
| Placebo | Participants With Adverse Events | Withdrawn due to treatment-related AE | 0 participants |
| Placebo | Participants With Adverse Events | Death | 0 participants |
| Placebo | Participants With Adverse Events | Serious AE (excluding death outcome) | 1 participants |
| Placebo | Participants With Adverse Events | At least 1 AE | 66 participants |
| Placebo | Participants With Adverse Events | Treatment-related serious AEs | 0 participants |
| Placebo | Participants With Adverse Events | Severe AE | 4 participants |
| Reslizumab - 0.3 mg/kg | Participants With Adverse Events | At least 1 AE | 59 participants |
| Reslizumab - 0.3 mg/kg | Participants With Adverse Events | Treatment-related AE | 6 participants |
| Reslizumab - 0.3 mg/kg | Participants With Adverse Events | Serious AE (excluding death outcome) | 0 participants |
| Reslizumab - 0.3 mg/kg | Participants With Adverse Events | Severe AE | 2 participants |
| Reslizumab - 0.3 mg/kg | Participants With Adverse Events | Withdrawn from study due to AE | 1 participants |
| Reslizumab - 0.3 mg/kg | Participants With Adverse Events | Death | 0 participants |
| Reslizumab - 0.3 mg/kg | Participants With Adverse Events | Treatment-related serious AEs | 0 participants |
| Reslizumab - 0.3 mg/kg | Participants With Adverse Events | Withdrawn due to treatment-related AE | 0 participants |
| Reslizumab - 3.0 mg/kg | Participants With Adverse Events | At least 1 AE | 61 participants |
| Reslizumab - 3.0 mg/kg | Participants With Adverse Events | Serious AE (excluding death outcome) | 4 participants |
| Reslizumab - 3.0 mg/kg | Participants With Adverse Events | Withdrawn due to treatment-related AE | 1 participants |
| Reslizumab - 3.0 mg/kg | Participants With Adverse Events | Death | 0 participants |
| Reslizumab - 3.0 mg/kg | Participants With Adverse Events | Treatment-related serious AEs | 0 participants |
| Reslizumab - 3.0 mg/kg | Participants With Adverse Events | Severe AE | 7 participants |
| Reslizumab - 3.0 mg/kg | Participants With Adverse Events | Treatment-related AE | 12 participants |
| Reslizumab - 3.0 mg/kg | Participants With Adverse Events | Withdrawn from study due to AE | 6 participants |
Secondary
Participants With a Positive Anti-Reslizumab Antibody Status at Baseline, Week 8, Week 16, Endpoint, and Overall
Counts of participants with a positive anti-drug antibody (ADA) response during treatment is offered for the two experimental treatment arms. Blood samples were collected for determination of ADAs before study drug infusion at baseline, visit 4 (week 8), and at visit 6 (week 16: EOT or early withdrawal) from patients in all 3 treatment groups (ie, placebo, 0.3 mg/kg reslizumab, and 3.0 mg/kg reslizumab); however, only the blood samples drawn from patients treated with either 0.3 mg/kg reslizumab or 3.0 mg/kg reslizumab were analyzed. Serum samples from patients who were treated with reslizumab were analyzed for ADA by Teva (Teva Biopharmaceuticals USA, Rockville, MD) using a validated homogeneous solution-based bridging enzyme-linked immunosorbent assay (ELISA). Endpoint =week 16 or early withdrawal.
Time frame: Day 1 (pre-dose), week 8, 16 and endpoint
Population: Pharmacokinetic analysis set. Anti-Reslizumab antibody status was not analyzed for patients in the Placebo treatment arm.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Reslizumab - 0.3 mg/kg | Participants With a Positive Anti-Reslizumab Antibody Status at Baseline, Week 8, Week 16, Endpoint, and Overall | Baseline (n=99, 98) | 8 participants |
| Reslizumab - 0.3 mg/kg | Participants With a Positive Anti-Reslizumab Antibody Status at Baseline, Week 8, Week 16, Endpoint, and Overall | Week 16 (n=91, 89) | 7 participants |
| Reslizumab - 0.3 mg/kg | Participants With a Positive Anti-Reslizumab Antibody Status at Baseline, Week 8, Week 16, Endpoint, and Overall | Week 8 (n=90, 94) | 8 participants |
| Reslizumab - 0.3 mg/kg | Participants With a Positive Anti-Reslizumab Antibody Status at Baseline, Week 8, Week 16, Endpoint, and Overall | Endpoint (n=101, 102) | 10 participants |
| Reslizumab - 0.3 mg/kg | Participants With a Positive Anti-Reslizumab Antibody Status at Baseline, Week 8, Week 16, Endpoint, and Overall | Overall (n=102, 103) | 12 participants |
| Reslizumab - 3.0 mg/kg | Participants With a Positive Anti-Reslizumab Antibody Status at Baseline, Week 8, Week 16, Endpoint, and Overall | Endpoint (n=101, 102) | 6 participants |
| Reslizumab - 3.0 mg/kg | Participants With a Positive Anti-Reslizumab Antibody Status at Baseline, Week 8, Week 16, Endpoint, and Overall | Overall (n=102, 103) | 11 participants |
| Reslizumab - 3.0 mg/kg | Participants With a Positive Anti-Reslizumab Antibody Status at Baseline, Week 8, Week 16, Endpoint, and Overall | Baseline (n=99, 98) | 8 participants |
| Reslizumab - 3.0 mg/kg | Participants With a Positive Anti-Reslizumab Antibody Status at Baseline, Week 8, Week 16, Endpoint, and Overall | Week 8 (n=90, 94) | 10 participants |
| Reslizumab - 3.0 mg/kg | Participants With a Positive Anti-Reslizumab Antibody Status at Baseline, Week 8, Week 16, Endpoint, and Overall | Week 16 (n=91, 89) | 5 participants |
Secondary
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values
Data represents participants with potentially clinically significant (PCS) abnormal serum chemistry, hematology (except for eosinophil values), and urinalysis values. Significance criteria: * Blood urea nitrogen: \>=10.71 mmol/L * Creatinine: \>=177 μmol/L * Uric acid: M\>=625, F\>=506 μmol/L * GGT = gamma-glutamyl transpeptidase: \>= 3\*upper limit of normal. Normal range is 5-49 U/L. * Total bilirubin: \>=34.2 μmol/L * White blood cells: \<=3.0 10\^9/L * Hemoglobin: M\<=115, F\<=95 g/dL * Hematocrit: M\<0.37, F\<0.32 % * Platelets: \>=700 10\^9/L * Absolute neutrophil count: \<=1.0 10\^9/L * Urinalysis: blood, glucose, ketones and total protein: \>=2 unit increase from baseline The last postbaseline value for approximately 10 patients in each treatment group is the 90-day follow-up visit post end-of-treatment (approx. Week 29).
Time frame: Day 2 to Week 29
Population: Safety analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Blood in urine | 10 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | >=1 PCS abnormal hematology value | 4 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Total bilirubin | 0 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Creatinine | 1 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | White blood cells | 0 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Ketones in urine | 0 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Blood urea nitrogen | 0 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Hemoglobin | 0 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | >=1 PCS abnormal urinalysis value | 21 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | >=1 PCS abnormal serum chemistry value | 1 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Hematocrit | 2 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Total protein in urine | 11 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Uric acid | 0 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Platelets | 0 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Glucose in urine | 3 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | GGT | 0 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Absolute neutrophil count | 2 participants |
| Reslizumab - 0.3 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | >=1 PCS abnormal serum chemistry value | 5 participants |
| Reslizumab - 0.3 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | >=1 PCS abnormal urinalysis value | 21 participants |
| Reslizumab - 0.3 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | GGT | 4 participants |
| Reslizumab - 0.3 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Blood in urine | 11 participants |
| Reslizumab - 0.3 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Blood urea nitrogen | 0 participants |
| Reslizumab - 0.3 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Glucose in urine | 4 participants |
| Reslizumab - 0.3 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Ketones in urine | 1 participants |
| Reslizumab - 0.3 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Total bilirubin | 1 participants |
| Reslizumab - 0.3 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Total protein in urine | 11 participants |
| Reslizumab - 0.3 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Absolute neutrophil count | 1 participants |
| Reslizumab - 0.3 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | >=1 PCS abnormal hematology value | 7 participants |
| Reslizumab - 0.3 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | White blood cells | 0 participants |
| Reslizumab - 0.3 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Creatinine | 0 participants |
| Reslizumab - 0.3 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Hemoglobin | 2 participants |
| Reslizumab - 0.3 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Hematocrit | 6 participants |
| Reslizumab - 0.3 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Platelets | 0 participants |
| Reslizumab - 0.3 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Uric acid | 0 participants |
| Reslizumab - 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Total protein in urine | 11 participants |
| Reslizumab - 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | >=1 PCS abnormal serum chemistry value | 2 participants |
| Reslizumab - 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Blood urea nitrogen | 1 participants |
| Reslizumab - 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Creatinine | 0 participants |
| Reslizumab - 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Uric acid | 2 participants |
| Reslizumab - 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | GGT | 0 participants |
| Reslizumab - 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Total bilirubin | 0 participants |
| Reslizumab - 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | >=1 PCS abnormal hematology value | 3 participants |
| Reslizumab - 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | White blood cells | 1 participants |
| Reslizumab - 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Hemoglobin | 0 participants |
| Reslizumab - 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Hematocrit | 2 participants |
| Reslizumab - 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Platelets | 1 participants |
| Reslizumab - 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Absolute neutrophil count | 0 participants |
| Reslizumab - 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | >=1 PCS abnormal urinalysis value | 18 participants |
| Reslizumab - 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Blood in urine | 6 participants |
| Reslizumab - 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Glucose in urine | 5 participants |
| Reslizumab - 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Ketones in urine | 3 participants |
Secondary
Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values
Data represents participants with potentially clinically significant (PCS) vital sign values. Significance criteria * Sitting pulse - high: \>100 and increase of \>= 30 beats/minute * Sitting pulse - low: \<50 and decrease of \>=30 beats/minute * Sitting diastolic blood pressure: \>100 and increase of \>=12 mmHg * Respiration rate: \>24 and increase of \>=10 breaths/minute * Body temperature: \<96.5° Fahrenheit or \<35.8° Celsius The last postbaseline value for approximately 10 patients in each treatment group is the 90-day follow-up visit post end-of-treatment (approx. Week 29).
Time frame: Day 2 to Week 29
Population: Safety analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | >=1 PCS abnormal vital sign | 12 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Sitting pulse - high | 0 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Sitting pulse - low | 0 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Sitting diastolic blood pressure - high | 0 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Respiration rate - high | 0 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Body temperature - low | 12 participants |
| Reslizumab - 0.3 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Body temperature - low | 13 participants |
| Reslizumab - 0.3 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | >=1 PCS abnormal vital sign | 16 participants |
| Reslizumab - 0.3 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Sitting diastolic blood pressure - high | 0 participants |
| Reslizumab - 0.3 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Respiration rate - high | 2 participants |
| Reslizumab - 0.3 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Sitting pulse - high | 1 participants |
| Reslizumab - 0.3 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Sitting pulse - low | 1 participants |
| Reslizumab - 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Sitting pulse - high | 2 participants |
| Reslizumab - 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Sitting pulse - low | 1 participants |
| Reslizumab - 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Body temperature - low | 13 participants |
| Reslizumab - 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Sitting diastolic blood pressure - high | 1 participants |
| Reslizumab - 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | >=1 PCS abnormal vital sign | 16 participants |
| Reslizumab - 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Respiration rate - high | 0 participants |
Secondary
Shifts From Baseline to Endpoint in Electrocardiogram Findings
Participant counts in each category of shift from baseline to endpoint of ECG finding. Findings summarized as normal or abnormal.
Time frame: Weeks -4 to -2 (Screening Visit), Week 16
Population: Safety analysis set of participants with both baseline and endpoint values.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Shifts From Baseline to Endpoint in Electrocardiogram Findings | Normal to Normal | 64 participants |
| Placebo | Shifts From Baseline to Endpoint in Electrocardiogram Findings | Abnormal to Abnormal | 13 participants |
| Placebo | Shifts From Baseline to Endpoint in Electrocardiogram Findings | Abnormal to Normal | 11 participants |
| Placebo | Shifts From Baseline to Endpoint in Electrocardiogram Findings | Normal to Abnormal | 14 participants |
| Reslizumab - 0.3 mg/kg | Shifts From Baseline to Endpoint in Electrocardiogram Findings | Normal to Abnormal | 10 participants |
| Reslizumab - 0.3 mg/kg | Shifts From Baseline to Endpoint in Electrocardiogram Findings | Abnormal to Normal | 9 participants |
| Reslizumab - 0.3 mg/kg | Shifts From Baseline to Endpoint in Electrocardiogram Findings | Abnormal to Abnormal | 10 participants |
| Reslizumab - 0.3 mg/kg | Shifts From Baseline to Endpoint in Electrocardiogram Findings | Normal to Normal | 70 participants |
| Reslizumab - 3.0 mg/kg | Shifts From Baseline to Endpoint in Electrocardiogram Findings | Abnormal to Abnormal | 10 participants |
| Reslizumab - 3.0 mg/kg | Shifts From Baseline to Endpoint in Electrocardiogram Findings | Normal to Normal | 63 participants |
| Reslizumab - 3.0 mg/kg | Shifts From Baseline to Endpoint in Electrocardiogram Findings | Abnormal to Normal | 13 participants |
| Reslizumab - 3.0 mg/kg | Shifts From Baseline to Endpoint in Electrocardiogram Findings | Normal to Abnormal | 15 participants |