Open-Label Extension Study to Evaluate the Long-Term Safety and Efficacy of Reslizumab (3.0 mg/kg) as Treatment for Patients (12 Through 75 Years of Age) With Eosinophilic Asthma

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 endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.

Population: Safety analysis set

Data represents participants with potentially clinically significant (PCS) abnormal serum chemistry, hematology, and urinalysis values on any of the during treatment lab analyses. Significance criteria: * Blood urea nitrogen: \>=10.71 mmol/L * Creatinine: \>=177 μmol/L * Uric acid: M\>=625, F\>=506 μmol/L * Aspartate aminotransferase: \>=3\*upper limit of normal (ULN). Normal range is 10-43 U/L * Alanine aminotransferase: \>=3\*ULN. Normal range is 10-40 U/L * GGT = gamma-glutamyl transpeptidase: \>= 3\*upper limit of normal. Normal range is 5-49 U/L. * Total bilirubin: \>=34.2 μmol/L * White blood cells- low: \<=3.0\*10\^9/L * White blood cells-high: \>=20\*10\^9/L * Hemoglobin: M\<=115, F\<=95 g/dL * Hematocrit: M\<0.37, F\<0.32 L/L * Platelets: \>=700\*10\^9/L * Absolute neutrophil count: \<=1.0\*10\^9/L * Eosinophils: \>=10 * Urinalysis: ketones, blood, glucose, and total protein: \>=2 unit increase from baseline

Time frame: Weeks 4, 8, 24 and 48

Population: Safety analysis set, including participants who contributed to the analysis

Data represents participants with PCS vital sign values during any of the during treatment visits or the follow-up visit. Significance criteria * Sitting heart rate-high: \>100 and increase of \>= 30 beats/min (all ages) * Sitting heart rate-low: \<50 and decrease of \>=30 beats/min * Sitting systolic blood pressure (BP)-high: \>130 and increase of \>=30 mmHg (ages 12-17) * Systolic BP-low: \<90 and decrease of \>=30 mmHg (ages \>=18) * Systolic BP-high: \>160 and increase of \>=30 mmHg (ages \>=18) * Sitting diastolic BP-low: \<55 and decrease of \>=12 mmHg (ages 12-17) * Diastolic BP-high: \>85 and increase of \>=12 mmHg (ages 12-17) * Diastolic BP-low: \<50 and decrease of \>=12 mmHg (ages \>=18) * Diastolic BP-high: \>100 and increase of \>=12 mmHg (ages \>=18) * Respiration rate: \>20 and increase of \>=10 breaths/minute (ages 12-17) * Respiration rate: \>24 and increase of \>=10 breaths/minute (ages \>=18) * Body temperature-low: \<96.5° Fahrenheit (all ages) * Body temp-high: \>100.5° F (all ages)

Time frame: Week 4 to Week 65

Population: Safety analysis set, including participants who contributed to the analysis

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.

Time frame: Weeks 4, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, end of study and endpoint

Population: Safety analysis set of participants with assessments at stated timeframes

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.

Time frame: Weeks 24, 48, 72, 96, End of Study and Endpoint

Population: Safety analysis set of participants with assessments at stated timeframes

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. .

Time frame: Weeks 4, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, end of study and endpoint

Population: Safety analysis set of participants with assessments at stated timeframes

SABA are used for quick relief of asthma symptoms. To measure SABA use, at each clinical visit participants 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. .

Time frame: Weeks 4, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, end of study and endpoint

Population: Safety analysis set of participants with assessments at stated timeframes

The FEF 25%-75% is the force expiratory flow at 25% to 75% of the Forced Vital Capacity (FVC), measured in liters/second .

Time frame: Weeks 4, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, end of study and endpoint

Population: Safety analysis set of participants with assessments at stated timeframes

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.

Time frame: Weeks 4, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, end of study and endpoint

Population: Safety analysis set of participants with assessments at stated timeframes

The FVC is the volume of air that can be forcibly blown out after full inspiration, measured in liters. .

Time frame: Weeks 4, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, end of study and endpoint

Population: Safety analysis set of participants with assessments at stated timeframes

Blood samples were collected for the determination of anti-drug antibody (ADAs) before study drug infusion at baseline and every 24 weeks until end of treatment visit or early withdrawal. Serum samples were analyzed by Teva (Teva Biopharmaceuticals USA, Rockville, Maryland, USA) using a validated homogeneous solution based bridging enzyme linked immune sorbent assay (Mikulsis et al 2011, Qui et al 2010). The analysis of anti-reslizumab antibody in patient serum consists of 3 tiers of assays for screening, confirmation, and titer analysis. If a participant had a treatment-emergent ADA response (ie, ADA positive at any of the postdose time points but negative at the predose time point) or if there was a treatment-boosted ADA response (defined as a greater than 4-fold increase from a positive baseline ADA response (Shankar et at 2014), the participant was classified as overall ADA positive. Predose samples for the reslizumab-experienced participants came from the previous studies.

Time frame: Baseline, Weeks 24, 48, 72, 96, End of Study, Endpoint and Overall

Population: Safety analysis set of participants with assessments at stated timeframes

The percent predicted FEV1 is the ratio of the volume of air expired in the first second of a forced expiration to the patient's predicted FEV based on a similar population without asthma. Percent predicted lung function values were transcribed directly from the lung function report to the CRF, without any calculation by Teva.

Time frame: Weeks 4, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, end of study and endpoint

Population: Safety analysis set of participants with assessments at stated timeframes