Eosinophilic Asthma
Conditions
Brief summary
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy, safety, and immunogenicity of treatment with reslizumab in patients with eosinophilic asthma.
Detailed description
Demonstrate the efficacy of reslizumab, at a dose of 3 mg/kg administered iv every 4 weeks over 12 months, as assessed by the reduction in frequency of clinical asthma exacerbations (CAEs) during 12 months. An exacerbation event will be considered a CAE if the patient meets either or both of the criteria listed below and this is corroborated with at least 1 other measurement to indicate the worsening of clinical signs and symptoms of asthma: * use of systemic, or an increase in the use of inhaled, corticosteroid treatment for 3 or more days * asthma-related emergency treatment The above criteria must be corroborated with at least 1 other measurement to indicate worsening in the clinical signs and symptoms of asthma.
Interventions
DRUGReslizumab
Patients were administered intravenously over 15 to 30 minutes reslizumab at a dosage of 3.0 mg/kg at baseline and once every 4 weeks relative to baseline over 48 weeks for a total of 13 doses.
DRUGPlacebo
Matching placebo (20 mM sodium acetate, 7% sucrose), administered intravenously (iv) once every 4 weeks over 52 weeks, for a total of 13 doses administered. Each patient received a specific volume of placebo to match the volume of reslizumab on the basis of the patient's body weight.
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
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. * The patient has had at least 1 asthma exacerbation requiring oral, intramuscular (im), or intravenous (iv) corticosteroid use for at least 3 days over the past 12 months before screening. * The patient has a current blood eosinophil level of at least 400/μl. * The patient has airway reversibility of at least 12% to beta-agonist administration. * The patient has an ACQ score of at least 1.5 at the screening and baseline (before the 1st dose of study drug) visits. * The patient is taking inhaled fluticasone at a dosage of at least 440 μg, or equivalent, daily. Chronic oral corticosteroid use (no more than 10 mg/day prednisone or equivalent) is allowed. If a patient is on a stable dose, eg, 2 weeks or more of oral corticosteroid treatment at the time of study enrollment, the patient must remain on this dose throughout the study. The patient's baseline asthma therapy regimen (including but not limited to inhaled corticosteroids, oral corticosteroids up to a maximum of 10 mg of prednisone daily or equivalent, leukotriene antagonists, 5-lipooxygenase inhibitors, or cromolyn) must be stable for 30 days prior to screening and baseline, and must continue without dosage changes throughout study. * All female patients must be surgically sterile, 2 years postmenopausal, or must have a negative pregnancy test ß-human chorionic gonadotropin \[ß-HCG\]) 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 participation in the study. * Written informed consent is obtained. Patients 12 through 17 years old must provide assent. * The patient is in reasonable health (except for diagnosis of asthma) as judged by the investigator, and as determined by a medical history, medical examination, ECG evaluation (at screening), serum chemistry, hematology, and urinalysis. * Other criteria apply; please contact the investigator for more information.
Exclusion criteria
* The patient has a clinically meaningful co-morbidity that would interfere with the study schedule or procedures, or compromise the patient's safety. * The patient has known hypereosinophilic syndrome. * The patient has another confounding underlying lung disorder (eg, chronic obstructive pulmonary disease, pulmonary fibrosis, or lung cancer). Patients with pulmonary conditions with symptoms of asthma and blood eosinophilia (eg, Churg-Strauss syndrome, allergic bronchopulmonary aspergillosis) will also be excluded. * The patient is a current smoker (ie, has smoked within the last 6 months prior to screening). * The patient is using systemic immunosuppressive or immunomodulating or other biologic agents (including, but not limited to, anti-IgE mAb, methotrexate, cyclosporin, interferon-α, or anti-tumor necrosis factor \[anti TNF\] mAb) within 6 months prior to screening. * The patient has previously received an anti-hIL-5 monoclonal antibody (eg, reslizumab, mepolizumab, or benralizumab). * The patient has any aggravating medical factors that are inadequately controlled (eg, rhinitis, gastroesophageal reflux disease, and uncontrolled diabetes). * 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 6 months prior to screening. * Female patients who are pregnant, nursing, or, if of childbearing potential, and not using a medically accepted, effective method of birth control (eg, barrier method with spermicide, abstinence, IUD, or steroidal contraceptive \[oral, transdermal, implanted, and injected\]) are excluded from this study. NOTE: Partner sterility alone is not considered an acceptable form of birth control. * Other criteria apply; please contact the investigator for more information.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Clinical Asthma Exacerbations (CAEs) During 12 Months of Treatment | Day 1 to Week 52 | An exacerbation event was considered a CAE if the patient met either or both of the criteria listed below and this was corroborated with at least 1 other measurement to indicate the worsening of clinical signs and symptoms of asthma: * use of systemic, or an increase in the use of inhaled, corticosteroid treatment for 3 or more days; or an increased 2 or more fold for at least 3 or more days for patient's already on corticosteroids. * asthma-related emergency treatment, such as an unscheduled visit to the physician's office or emergency room for nebulizer treatment or other urgent treatment to prevent worsening of asthma symptoms, or an asthma-related hospitalization CAEs were adjudicated by committee to assure consistency. Adjusted CAE rate and confidence intervals were based on Negative Binomial regression model adjusted for stratification factors. Results are offered as adjusted means. |
| Frequency of Each of the Two Criteria for Clinical Asthma Exacerbations (CAEs) | Day 1 to Week 52 | An exacerbation event was considered a CAE if the patient met either or both of the criteria listed below and this was corroborated with at least 1 other measurement to indicate the worsening of clinical signs and symptoms of asthma: * use of systemic, or an increase in the use of inhaled, corticosteroid treatment for 3 or more days; or an increased 2 or more fold for at least 3 or more days for patient's already on corticosteroids. * asthma-related emergency treatment, such as an unscheduled visit to the physician's office or emergency room for nebulizer treatment or other urgent treatment to prevent worsening of asthma symptoms, or an asthma-related hospitalization. CAEs were adjudicated by committee to assure consistency. Adjusted CAE rate and confidence intervals for the two criteria were based on Negative Binomial regression model adjusted for stratification factors. Results are offered as adjusted means. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Kaplan-Meier Estimates for Time to First Clinical Asthma Exacerbation (CAE) | Day 1 to Day 478 (longest treatment time plus 2 weeks) | An exacerbation event was considered a CAE if the patient met either or both of the criteria listed below and this was corroborated with at least 1 other measurement to indicate the worsening of clinical signs and symptoms of asthma: * use of systemic, or an increase in the use of inhaled, corticosteroid treatment for 3 or more days; or an increased 2 or more fold for at least 3 or more days for patient's already on corticosteroids. * asthma-related emergency treatment, such as an unscheduled visit to the physician's office or emergency room for nebulizer treatment or other urgent treatment to prevent worsening of asthma symptoms, or an asthma-related hospitalization. CAEs were adjudicated by committee to assure consistency. The distributions were compared by a log rank test stratified by baseline usage of oral corticosteroid (yes or no) and geographical region (US or other). |
| 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; info obtained from questionnaire about asthma symptoms. 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) 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 Expiratory Volume in 1 Second (FEV1) Over 16 Weeks Using Mixed Model for Repeated Measures | Day 1 (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. Positive change from baseline scores indicate improvement in asthma control. 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. |
| Participants With Treatment-Emergent Adverse Events | Day 1 (post-dose) to Week 65. The last postbaseline value for approximately 20 patients in each | 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. |
| Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Week 4 to Week 65. The last postbaseline value for approximately 20 patients in each | Data represents participants with potentially clinically significant (PCS) abnormal serum chemistry, hematology, and urinalysis values. Significance criteria: * Blood urea nitrogen: \>=10.71 mmol/L * Uric acid: M\>=625, F\>=506 μmol/L * Aspartate aminotransferase: \>=3\*upper limit of normal (ULN). Normal range is 10-43 U/L * Alanine aminotransferase: \>=3\*ULN. Normal range is 10-40 U/L * GGT = gamma-glutamyl transpeptidase: \>= 3\*ULN. Normal range is 5-49 U/L. * Bilirubin: \>=34.2 μmol/L * White blood cells: \<=3.0 or \>20 10\^9/L * Hemoglobin: M\<=115, F\<=95 g/dL * Hematocrit: M\<0.37, F\<0.32 L/L * Neutrophils: \<=1.0 10\^9/L * Eosinophils: \>10.0 % * Platelets: \<75 or \>=700 10\^9/L * Urinalysis: blood, glucose, ketones and total protein: \>=2 unit increase from baseline |
| Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Week 4 to Week 65. The last postbaseline value for approximately 20 patients in each | Data represents participants with potentially clinically significant (PCS) vital sign values. Significance criteria * Sitting pulse - high 12-17 yr: \>100 and increase of \>= 30 beats/minute (bpm) * Sitting pulse - low \>=18 yr: \<50 and decrease of \>=30 bpm * Sitting pulse - high \>=18 yr: \>100 and increase of \>=30 bpm * Sitting systolic blood pressure - low \>=18 yr: \<90 and decrease of \>=30 mmHg * Sitting systolic blood pressure - high \>=18 yr: \>160 and increase of \>=30 mmHg * Sitting diastolic blood pressure - low 12-17 yr: \<55 and decrease of \>=12 mmHg * Sitting diastolic blood pressure - low \>=18 yr: \<50 and decrease of \>=12 mmHg * Sitting diastolic blood pressure - high \>=18 yr: \>100 and increase of \>=12 mmHg * Respiratory rate \>=18 yr: \>24 and increase of \>=10 breaths/minute * Body temperature - low 12-17 yr: \<96.5° Fahrenheit or \<35.8° Celsius * Body temp - low \>=18 yr: \<96.5° F or \<35.8° C * Body temp - high \>=18 yr: \>100.5° Fahrenheit |
| Participants With a Positive Anti-Reslizumab Antibody Status During Study | Weeks 16, 32, 48 and 52 | The immunogenicity of reslizumab was assessed by measuring for the presence of anti-reslizumab antibodies at baseline, weeks 16, 32, 48, and 52 or early withdrawal. Blood samples for anti-reslizumab antibodies assessment were also obtained from all patients (inside or outside of the US) experiencing a serious adverse event, an adverse event leading to withdrawal, or an exacerbation of asthma symptoms. |
| Change From Baseline in Blood Eosinophil Count Over 16 Weeks and 52 Weeks Using Mixed Model for Repeated Measures | Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 or early withdrawal | 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 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. |
| Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) to Week 16 | Day 1 (baseline, pre-dose), Week 16 | 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. |
Countries
Australia, Belgium, Chile, Colombia, Czechia, Denmark, Hungary, Israel, Malaysia, New Zealand, Philippines, Poland, Russia, South Africa, Sweden, Thailand, United States
Participant flow
Recruitment details
A total of 1486 patients were screened at 121 centers. Of the 1486 patients screened, 489 patients with asthma and blood eosinophils ≥400/ μL at 102 centers in 17 countries were randomly assigned to double-blind treatment.
Pre-assignment details
997 of 1486 screened patients were not randomized: 888 were excluded on the basis of not meeting inclusion criteria, 23 withdrew consent, 17 had an adverse event during the screening period, 12 met an exclusion criterion, 7 were lost to follow-up and 50 were excluded for other reasons. One placebo patient was randomized but not treated.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses. | 244 |
| Reslizumab 3.0 mg/kg Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses. | 245 |
| Total | 489 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 7 | 4 |
| Overall Study | Change of location/residence | 0 | 3 |
| Overall Study | Change of residence | 1 | 0 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Elective surgery | 0 | 1 |
| Overall Study | Excluded medication taken | 1 | 0 |
| Overall Study | Lost to Follow-up | 3 | 2 |
| Overall Study | Noncompliance with study medication | 0 | 1 |
| Overall Study | Noncompliance with study procedures | 0 | 1 |
| Overall Study | Problem with travel | 0 | 1 |
| Overall Study | Protocol Violation | 2 | 3 |
| Overall Study | Withdrawal by Subject | 14 | 11 |
Baseline characteristics
| Characteristic | Placebo | Total | Reslizumab 3.0 mg/kg |
|---|---|---|---|
| Age, Continuous | 46.7 years STANDARD_DEVIATION 14.83 | 46.6 years STANDARD_DEVIATION 14.32 | 46.6 years STANDARD_DEVIATION 13.82 |
| Asthma Control Questionnaire (ACQ) Overall Score | 2.763 units on a scale STANDARD_DEVIATION 0.8782 | 2.710 units on a scale STANDARD_DEVIATION 0.867 | 2.657 units on a scale STANDARD_DEVIATION 0.8541 |
| Asthma Exacerbations In Previous 12 Months | 2.1 exacerbations STANDARD_DEVIATION 2.31 | 2.0 exacerbations STANDARD_DEVIATION 2 | 1.9 exacerbations STANDARD_DEVIATION 1.63 |
| Asthma Quality of Life Questionnaire (AQLQ) | 4.159 units on a scale STANDARD_DEVIATION 1.0883 | 4.231 units on a scale STANDARD_DEVIATION 1.1059 | 4.303 units on a scale STANDARD_DEVIATION 1.1208 |
| Asthma Symptom Utility Index (ASUI) | 0.613 units on a scale STANDARD_DEVIATION 0.2029 | 0.623 units on a scale STANDARD_DEVIATION 0.1984 | 0.633 units on a scale STANDARD_DEVIATION 0.1938 |
| Body Mass Index | 28.0 kg/m^2 STANDARD_DEVIATION 6.16 | 27.9 kg/m^2 STANDARD_DEVIATION 6.2 | 27.7 kg/m^2 STANDARD_DEVIATION 6.26 |
| Forced Expiratory Volume in 1 Second | 1.928 liters STANDARD_DEVIATION 0.7908 | 1.911 liters STANDARD_DEVIATION 0.7583 | 1.894 liters STANDARD_DEVIATION 0.7258 |
| Height | 165.0 cm STANDARD_DEVIATION 9.74 | 164.9 cm STANDARD_DEVIATION 10.07 | 164.9 cm STANDARD_DEVIATION 10.42 |
| Number of Short-Acting Beta-Agonist Puffs (SABA) Daily | 2.7 puffs/day STANDARD_DEVIATION 3.18 | 2.6 puffs/day STANDARD_DEVIATION 3.01 | 2.4 puffs/day STANDARD_DEVIATION 2.82 |
| Oral Glucocorticosteroid (OCS) Use at Baseline OCS - No | 198 participants | 397 participants | 199 participants |
| Oral Glucocorticosteroid (OCS) Use at Baseline OCS - Yes | 46 participants | 92 participants | 46 participants |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Asian | 33 participants | 83 participants | 50 participants |
| Race/Ethnicity, Customized Black | 20 participants | 34 participants | 14 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 21 participants | 49 participants | 28 participants |
| Race/Ethnicity, Customized Non-Hispanic and non-Latino | 223 participants | 439 participants | 216 participants |
| Race/Ethnicity, Customized Other | 9 participants | 16 participants | 7 participants |
| Race/Ethnicity, Customized Pacific Islander | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Unknown | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized White | 182 participants | 355 participants | 173 participants |
| Sex: Female, Male Female | 161 Participants | 303 Participants | 142 Participants |
| Sex: Female, Male Male | 83 Participants | 186 Participants | 103 Participants |
| Weight | 76.5 kg STANDARD_DEVIATION 18.71 | 76.0 kg STANDARD_DEVIATION 18.87 | 75.6 kg STANDARD_DEVIATION 19.05 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 184 / 243 | 165 / 245 |
| serious Total, serious adverse events | 34 / 243 | 24 / 245 |
Outcome results
Primary
Frequency of Clinical Asthma Exacerbations (CAEs) During 12 Months of Treatment
An exacerbation event was considered a CAE if the patient met either or both of the criteria listed below and this was corroborated with at least 1 other measurement to indicate the worsening of clinical signs and symptoms of asthma: * use of systemic, or an increase in the use of inhaled, corticosteroid treatment for 3 or more days; or an increased 2 or more fold for at least 3 or more days for patient's already on corticosteroids. * asthma-related emergency treatment, such as an unscheduled visit to the physician's office or emergency room for nebulizer treatment or other urgent treatment to prevent worsening of asthma symptoms, or an asthma-related hospitalization CAEs were adjudicated by committee to assure consistency. Adjusted CAE rate and confidence intervals were based on Negative Binomial regression model adjusted for stratification factors. Results are offered as adjusted means.
Time frame: Day 1 to Week 52
Population: Randomized set
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Frequency of Clinical Asthma Exacerbations (CAEs) During 12 Months of Treatment | 1.804 CAEs in 52 weeks |
| Reslizumab 3.0 mg/kg | Frequency of Clinical Asthma Exacerbations (CAEs) During 12 Months of Treatment | 0.904 CAEs in 52 weeks |
Comparison: The frequency of CAEs was analyzed using the generalized linear model (GLM) for data from the negative binomial distributions that is commonly referred to as the negative binomial (NB) regression model. The primary NB model included the treatment group and randomization stratification factors as model factors and the logarithm of follow up time excluding the summed duration of exacerbations in the treatment period as an offset variable.p-value: <0.000195% CI: [0.3726, 0.6737]Chi-squared
Primary
Frequency of Each of the Two Criteria for Clinical Asthma Exacerbations (CAEs)
An exacerbation event was considered a CAE if the patient met either or both of the criteria listed below and this was corroborated with at least 1 other measurement to indicate the worsening of clinical signs and symptoms of asthma: * use of systemic, or an increase in the use of inhaled, corticosteroid treatment for 3 or more days; or an increased 2 or more fold for at least 3 or more days for patient's already on corticosteroids. * asthma-related emergency treatment, such as an unscheduled visit to the physician's office or emergency room for nebulizer treatment or other urgent treatment to prevent worsening of asthma symptoms, or an asthma-related hospitalization. CAEs were adjudicated by committee to assure consistency. Adjusted CAE rate and confidence intervals for the two criteria were based on Negative Binomial regression model adjusted for stratification factors. Results are offered as adjusted means.
Time frame: Day 1 to Week 52
Population: Randomized set
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Placebo | Frequency of Each of the Two Criteria for Clinical Asthma Exacerbations (CAEs) | Requiring systemic corticosterioids >3 days | 1.604 CAEs in 52 weeks |
| Placebo | Frequency of Each of the Two Criteria for Clinical Asthma Exacerbations (CAEs) | Requiring hospitalization or ER visit | 0.207 CAEs in 52 weeks |
| Reslizumab 3.0 mg/kg | Frequency of Each of the Two Criteria for Clinical Asthma Exacerbations (CAEs) | Requiring systemic corticosterioids >3 days | 0.722 CAEs in 52 weeks |
| Reslizumab 3.0 mg/kg | Frequency of Each of the Two Criteria for Clinical Asthma Exacerbations (CAEs) | Requiring hospitalization or ER visit | 0.137 CAEs in 52 weeks |
Comparison: CAE Due to Requiring Systemic Corticosteroids The frequency of CAEs was analyzed using the generalized linear model (GLM) for data from the negative binomial distributions that is commonly referred to as the negative binomial (NB) regression model. The primary NB model included the treatment group and randomization stratification factors as model factors and the logarithm of follow up time excluding the summed duration of exacerbations in the treatment period as an offset variable.p-value: <0.000195% CI: [0.3255, 0.622]Chi-squared
Comparison: CAE Due to Hospitalization or ER visit The frequency of CAEs was analyzed using the generalized linear model (GLM) for data from the negative binomial distributions that is commonly referred to as the negative binomial (NB) regression model. The primary NB model included the treatment group and randomization stratification factors as model factors and the logarithm of follow up time excluding the summed duration of exacerbations in the treatment period as an offset variable.p-value: 0.257295% CI: [0.321, 1.355]Chi-squared
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: Randomized 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 | -0.676 units on a scale | Standard Error 0.066 |
| Reslizumab 3.0 mg/kg | Change From Baseline in Asthma Control Questionnaire (ACQ) Over 16 Weeks Using Mixed Model for Repeated Measures | -0.941 units on a scale | Standard Error 0.065 |
Comparison: For each week and overall change, inferential statistics were from mixed model repeated measures (MMRM) with treatment, visit, treatment by visit interaction, region, oral glucocorticosteroids use at enrollment and sex as fixed factors, and covariates for height and baseline value and patient as a random effect. Unstructured covariance structure was assumed for the repeated measures.p-value: 0.000195% CI: [-0.399, -0.132]Mixed model repeated measures
Secondary
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) to Week 16
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.
Time frame: Day 1 (baseline, pre-dose), Week 16
Population: Randomized set of patients with assessments at both timepoints
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) to Week 16 | 0.695 units on a scale | Standard Error 0.088 |
| Reslizumab 3.0 mg/kg | Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) to Week 16 | 0.933 units on a scale | Standard Error 0.088 |
Comparison: For each week and overall change, inferential statistics were from mixed model repeated measures (MMRM) with treatment, visit, treatment by visit interaction, region, oral glucocorticosteroids use at enrollment and sex as fixed factors, and covariates for height and baseline value and patient as a random effect. Unstructured covariance structure was assumed for the repeated measures.p-value: 0.014395% CI: [0.048, 0.428]Mixed model repeated measures
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; info obtained from questionnaire about asthma symptoms. 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: Randomized set, including participants 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 | 0.109 units on a scale | Standard Error 0.012 |
| Reslizumab 3.0 mg/kg | Change From Baseline in Asthma Symptom Utility Index (ASUI) Over 16 Weeks Using Mixed Model for Repeated Measures | 0.167 units on a scale | Standard Error 0.188 |
Comparison: For each week, inferential statistics were from mixed model repeated measures (MMRM) with treatment, visit, treatment by visit interaction, region, oral glucocorticosteroids use at enrollment as fixed factor, and covariate baseline value and patient as a random effect. Unstructured covariance structure was assumed for the repeated measures.p-value: <0.000195% CI: [0.034, 0.083]Mixed model repeated measures
Secondary
Change From Baseline in Blood Eosinophil Count Over 16 Weeks and 52 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 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, 20, 24, 28, 32, 36, 40, 44, 48, 52 or early withdrawal
Population: Randomized set of participants with assessments within timeframe
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Blood Eosinophil Count Over 16 Weeks and 52 Weeks Using Mixed Model for Repeated Measures | Over first 16 weeks | -0.118 10^9 blood eosinophil/L | Standard Error 0.0232 |
| Placebo | Change From Baseline in Blood Eosinophil Count Over 16 Weeks and 52 Weeks Using Mixed Model for Repeated Measures | Over 52 weeks | -0.127 10^9 blood eosinophil/L | Standard Error 0.0168 |
| Reslizumab 3.0 mg/kg | Change From Baseline in Blood Eosinophil Count Over 16 Weeks and 52 Weeks Using Mixed Model for Repeated Measures | Over first 16 weeks | -0.584 10^9 blood eosinophil/L | Standard Error 0.023 |
| Reslizumab 3.0 mg/kg | Change From Baseline in Blood Eosinophil Count Over 16 Weeks and 52 Weeks Using Mixed Model for Repeated Measures | Over 52 weeks | -0.582 10^9 blood eosinophil/L | Standard Error 0.0167 |
Comparison: Eosinophil Count Over 16 Weeks~Inferential statistics were from mixed model repeated measures (MMRM) with treatment, visit, treatment by visit interaction, region, oral glucocorticosteroids use at enrollment as fixed factor, and covariate baseline value and patient as a random effect. Unstructured covariance structure was assumed for the repeated measures.p-value: <0.000195% CI: [-0.514, -0.418]Mixed model repeated measures
Comparison: Eosinophil Count Over 52 Weeks~Inferential statistics were from mixed model repeated measures (MMRM) with treatment, visit, treatment by visit interaction, region, oral glucocorticosteroids use at enrollment as fixed factor, and covariate baseline value and patient as a random effect. Unstructured covariance structure was assumed for the repeated measures.p-value: <0.000195% CI: [-0.491, -0.419]Mixed model repeated measures
Secondary
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. Positive change from baseline scores indicate improvement in asthma control. 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.
Time frame: Day 1 (baseline, pre-dose), Weeks 4, 8, 12 and 16
Population: Randomized set, including participants 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 | 0.110 liters | Standard Error 0.031 |
| 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 | 0.248 liters | Standard Error 0.03 |
Comparison: For each week and overall change, inferential statistics were from mixed model repeated measures (MMRM) with treatment, visit, treatment by visit interaction, region, oral glucocorticosteroids use at enrollment and sex as fixed factors, and covariates for height and baseline value and patient as a random effect. Unstructured covariance structure was assumed for the repeated measures.p-value: <0.000195% CI: [0.076, 0.198]Mixed Model Repeated Measures
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) 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: Randomized set of participants with assessments within the timeframe
| 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 | -0.36 puffs/day | Standard Error 0.158 |
| Reslizumab 3.0 mg/kg | Change From Baseline in Short-Acting Beta-Agonist (SABA) Use Over 16 Weeks Using Mixed Model for Repeated Measures | -0.64 puffs/day | Standard Error 0.156 |
Comparison: Inferential statistics were from mixed model repeated measures (MMRM) with treatment, visit, treatment by visit interaction, region, OCS use at enrollment as fixed factors, and covariate for baseline value and patient as a random effect. Unstructured covariance structure was assumed for the repeated measures.p-value: 0.091995% CI: [-0.597, 0.045]Mixed model repeated measures
Secondary
Kaplan-Meier Estimates for Time to First Clinical Asthma Exacerbation (CAE)
An exacerbation event was considered a CAE if the patient met either or both of the criteria listed below and this was corroborated with at least 1 other measurement to indicate the worsening of clinical signs and symptoms of asthma: * use of systemic, or an increase in the use of inhaled, corticosteroid treatment for 3 or more days; or an increased 2 or more fold for at least 3 or more days for patient's already on corticosteroids. * asthma-related emergency treatment, such as an unscheduled visit to the physician's office or emergency room for nebulizer treatment or other urgent treatment to prevent worsening of asthma symptoms, or an asthma-related hospitalization. CAEs were adjudicated by committee to assure consistency. The distributions were compared by a log rank test stratified by baseline usage of oral corticosteroid (yes or no) and geographical region (US or other).
Time frame: Day 1 to Day 478 (longest treatment time plus 2 weeks)
Population: Randomized set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Kaplan-Meier Estimates for Time to First Clinical Asthma Exacerbation (CAE) | 34.9 weeks |
| Reslizumab 3.0 mg/kg | Kaplan-Meier Estimates for Time to First Clinical Asthma Exacerbation (CAE) | NA weeks |
Comparison: Kaplan-Meier estimate of probability (5) of not experiencing a CAE by week 52. The first CAEs for each patient occurring after randomization and up to 2 weeks after the end of treatment period were analyzed. Patients without a CAE within this time frame were censored at two weeks after the treatment completion date or study discontinuation, whichever came first.p-value: <0.000195% CI: [0.44, 0.75]Regression, Cox
Secondary
Participants With a Positive Anti-Reslizumab Antibody Status During Study
The immunogenicity of reslizumab was assessed by measuring for the presence of anti-reslizumab antibodies at baseline, weeks 16, 32, 48, and 52 or early withdrawal. Blood samples for anti-reslizumab antibodies assessment were also obtained from all patients (inside or outside of the US) experiencing a serious adverse event, an adverse event leading to withdrawal, or an exacerbation of asthma symptoms.
Time frame: Weeks 16, 32, 48 and 52
Population: Safety analysis set. Immunogenicity for anti-reslizumab antibodies not reported for the placebo treatment arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Reslizumab 3.0 mg/kg | Participants With a Positive Anti-Reslizumab Antibody Status During Study | 8 participants |
Secondary
Participants With Treatment-Emergent 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.
Time frame: Day 1 (post-dose) to Week 65. The last postbaseline value for approximately 20 patients in each
Population: Safety analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Participants With Treatment-Emergent Adverse Events | Serious AE | 34 participants |
| Placebo | Participants With Treatment-Emergent Adverse Events | Mild severity AE | 41 participants |
| Placebo | Participants With Treatment-Emergent Adverse Events | AE causing patient discontinuation | 8 participants |
| Placebo | Participants With Treatment-Emergent Adverse Events | Moderate severity AE | 133 participants |
| Placebo | Participants With Treatment-Emergent Adverse Events | Deaths | 1 participants |
| Placebo | Participants With Treatment-Emergent Adverse Events | Severe AE | 32 participants |
| Placebo | Participants With Treatment-Emergent Adverse Events | Treatment-related severe AE | 0 participants |
| Placebo | Participants With Treatment-Emergent Adverse Events | Treatment-related AE | 36 participants |
| Placebo | Participants With Treatment-Emergent Adverse Events | At least 1 AE | 206 participants |
| Placebo | Participants With Treatment-Emergent Adverse Events | Treatment-related mild AE | 23 participants |
| Placebo | Participants With Treatment-Emergent Adverse Events | Treatment-related moderate AE | 13 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Adverse Events | Treatment-related mild AE | 24 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Adverse Events | Treatment-related moderate AE | 9 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Adverse Events | Treatment-related severe AE | 3 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Adverse Events | AE causing patient discontinuation | 4 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Adverse Events | Serious AE | 24 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Adverse Events | Deaths | 0 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Adverse Events | At least 1 AE | 197 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Adverse Events | Mild severity AE | 68 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Adverse Events | Moderate severity AE | 107 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Adverse Events | Severe AE | 22 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Adverse Events | Treatment-related AE | 36 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, and urinalysis values. Significance criteria: * Blood urea nitrogen: \>=10.71 mmol/L * Uric acid: M\>=625, F\>=506 μmol/L * Aspartate aminotransferase: \>=3\*upper limit of normal (ULN). Normal range is 10-43 U/L * Alanine aminotransferase: \>=3\*ULN. Normal range is 10-40 U/L * GGT = gamma-glutamyl transpeptidase: \>= 3\*ULN. Normal range is 5-49 U/L. * Bilirubin: \>=34.2 μmol/L * White blood cells: \<=3.0 or \>20 10\^9/L * Hemoglobin: M\<=115, F\<=95 g/dL * Hematocrit: M\<0.37, F\<0.32 L/L * Neutrophils: \<=1.0 10\^9/L * Eosinophils: \>10.0 % * Platelets: \<75 or \>=700 10\^9/L * Urinalysis: blood, glucose, ketones and total protein: \>=2 unit increase from baseline
Time frame: Week 4 to Week 65. The last postbaseline value for approximately 20 patients in each
Population: Safety analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Blood urea nitrogen | 9 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Uric acid | 9 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Aspartate aminotransferase | 1 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Alanine aminotransferase | 3 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Gamma-glutamyl transpeptidase | 12 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Bilirubin | 2 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | White blood cells - low | 6 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | White blood cells - high | 5 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Hemoglobin | 7 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Hematocrit | 9 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Neutrophils | 8 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Eosinophils | 135 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Platelets - low | 1 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Platelets - high | 2 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Urinalysis - Blood (hemoglobin) | 32 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Urinalysis - Ketones | 4 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Urinalysis - Glucose | 11 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Urinalysis - Protein | 32 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Platelets - high | 0 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Blood urea nitrogen | 8 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Hematocrit | 6 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Uric acid | 6 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Urinalysis - Protein | 34 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Aspartate aminotransferase | 1 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Neutrophils | 6 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Alanine aminotransferase | 5 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Urinalysis - Blood (hemoglobin) | 21 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Gamma-glutamyl transpeptidase | 12 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Eosinophils | 3 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Bilirubin | 1 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Urinalysis - Glucose | 14 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | White blood cells - low | 6 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Platelets - low | 2 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | White blood cells - high | 3 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Urinalysis - Ketones | 5 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values | Hemoglobin | 4 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 12-17 yr: \>100 and increase of \>= 30 beats/minute (bpm) * Sitting pulse - low \>=18 yr: \<50 and decrease of \>=30 bpm * Sitting pulse - high \>=18 yr: \>100 and increase of \>=30 bpm * Sitting systolic blood pressure - low \>=18 yr: \<90 and decrease of \>=30 mmHg * Sitting systolic blood pressure - high \>=18 yr: \>160 and increase of \>=30 mmHg * Sitting diastolic blood pressure - low 12-17 yr: \<55 and decrease of \>=12 mmHg * Sitting diastolic blood pressure - low \>=18 yr: \<50 and decrease of \>=12 mmHg * Sitting diastolic blood pressure - high \>=18 yr: \>100 and increase of \>=12 mmHg * Respiratory rate \>=18 yr: \>24 and increase of \>=10 breaths/minute * Body temperature - low 12-17 yr: \<96.5° Fahrenheit or \<35.8° Celsius * Body temp - low \>=18 yr: \<96.5° F or \<35.8° C * Body temp - high \>=18 yr: \>100.5° Fahrenheit
Time frame: Week 4 to Week 65. The last postbaseline value for approximately 20 patients in each
Population: Safety analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Sitting pulse - high 12-17 yr | 1 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Sitting pulse - low >=18 yr | 1 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Sitting pulse - high >=18 yr | 5 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Sitting systolic blood pressure - low >=18 yr | 2 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Sitting systolic blood pressure - high >=18 yr | 7 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Sitting diastolic blood pressure - low 12-17 yr | 1 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Sitting diastolic blood pressure - low >=18 yr | 0 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Sitting diastolic blood pressure - high >=18 yr | 10 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Respiratory rate >=18 yr | 3 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Body temperature - low 12-17 yr | 1 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Body temperature - low >=18 yr | 54 participants |
| Placebo | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Body temperature - high >=18 yr | 0 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Body temperature - low >=18 yr | 49 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Sitting pulse - high 12-17 yr | 1 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Sitting diastolic blood pressure - low >=18 yr | 1 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Sitting pulse - low >=18 yr | 0 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Body temperature - low 12-17 yr | 1 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Sitting pulse - high >=18 yr | 7 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Sitting diastolic blood pressure - high >=18 yr | 5 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Sitting systolic blood pressure - low >=18 yr | 5 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Body temperature - high >=18 yr | 1 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Sitting systolic blood pressure - high >=18 yr | 7 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Respiratory rate >=18 yr | 2 participants |
| Reslizumab 3.0 mg/kg | Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values | Sitting diastolic blood pressure - low 12-17 yr | 0 participants |