A Study to Evaluate the Efficacy and Safety of Reslizumab (3.0 mg/kg) in the Reduction of Clinical Asthma Exacerbations and Change in Lung Function in Patients (12-75 Years of Age) With Eosinophilic Asthma

• Overall change in forced expiratory volume in 1 second (FEV1) [ Time Frame: From baseline to Week 16, or the onset of first CAE, whichever occurs first ] [ Designated as safety issue: No ]
• A reduction in the frequency (i.e., number) of clinical asthma exacerbations (CAEs) [ Time Frame: From baseline to Week 52 ] [ Designated as safety issue: No ]

• Lung function as measured by Forced Expiratory Volume (FEV1) [ Time Frame: At baseline and at weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 or early withdrawal, or at time of first CAE ] [ Designated as safety issue: No ]
• Lung function as measured by percent predicted Forced Expiratory Volume in 1 second (%FEV1) [ Time Frame: At baseline and at weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 or early withdrawal, or at time of first CAE ] [ Designated as safety issue: No ]
• Lung function as measured by Forced Vital Capacity (FVC) [ Time Frame: At baseline and at weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 or early withdrawal, or at time of first CAE ] [ Designated as safety issue: No ]
• Lung function as measured by Forced Expiratory Flow at 25% to 75% of FVC (FEF25-75%) [ Time Frame: At baseline and at weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 or early withdrawal, or at time of first CAE ] [ Designated as safety issue: No ]
• Measurement of time to first clinical asthma exacerbation (CAE) [ Time Frame: From baseline to Week 52 ] [ Designated as safety issue: No ]
• Document the courses of oral corticosteroids prescribed for asthma worsening (3 or more days of administration or doubling of current dose) [ Time Frame: From Baseline to Week 52 or early withdrawal, or at time of first CAE ] [ Designated as safety issue: No ]
• Short-acting Beta-agonist usage [ Time Frame: From baseline to Week 52 or early withdrawal, or at time of first CAE ] [ Designated as safety issue: No ]
• Blood eosinophil count [ Time Frame: At baseline and at weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 or early withdrawal, or at time of first CAE ] [ Designated as safety issue: No ]
• Asthma symptoms as measured by the Asthma Symptom Utility Index (ASUI) [ Time Frame: At baseline and at weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 or early withdrawal, or at time of first CAE ] [ Designated as safety issue: No ]
• Asthma control as measured by the Asthma Control Questionnaire (ACQ) [ Time Frame: At baseline and at weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52 or early withdrawal, or at time of first CAE ] [ Designated as safety issue: No ]
• Quality of life as measured by the Asthma Quality of Life Questionnaire (AQLQ) [ Time Frame: At baseline and Weeks 16, 32, and 52 or early withdrawal, or at time of first CAE ] [ Designated as safety issue: No ]
• Safety and tolerability of reslizumab treatment in patients with eosinophilic asthma [ Time Frame: Throughout the 2- to 4-week screening period, 52-week double-blind treatment period, and at a 90-day follow-up evaluation ] [ Designated as safety issue: Yes ]

• Lung function as measured by Forced Expiratory Volume (FEV1) [ Designated as safety issue: No ]
• Lung function as measured by percent predicted Forced Expiratory Volume in 1 second (%FEV1) [ Designated as safety issue: No ]
• Lung function as measured by Forced Vital Capacity (FVC) [ Designated as safety issue: No ]
• Lung function as measured by Forced Expiratory Flow at 25% to 75% of FVC (FEF25-75%) [ Designated as safety issue: No ]
• Measurement of time to first clinical asthma exacerbation (CAE) [ Designated as safety issue: No ]
• Document the courses of oral corticosteroids prescribed for asthma worsening (3 or more days of administration or doubling of current dose) [ Designated as safety issue: No ]
• Short-acting Beta-agonist usage [ Time Frame: during the entire 52 week treatment period ] [ Designated as safety issue: No ]
• Blood eosinophil count [ Designated as safety issue: No ]
• Asthma symptoms as measured by the Asthma Symptom Utility Index (ASUI) [ Designated as safety issue: No ]
• Asthma control as measured by the Asthma Control Questionnaire (ACQ) [ Designated as safety issue: No ]
• Quality of life as measured by the Asthma Quality of Life Questionnaire (AQLQ) [ Designated as safety issue: No ]
• Safety and tolerability of reslizumab treatment in patients with eosinophilic asthma [ Time Frame: during the entire 52 week treatment period ] [ Designated as safety issue: Yes ]

The primary objective of this study is to demonstrate the efficacy of reslizumab, at a dose of 3 mg/kg administered intravenously every 4 weeks over 12 months, as assessed by the reduction in frequency of clinical asthma exacerbations (CAEs) during 12 months and by the overall change in forced expiratory volume in 1 second (FEV1) during the first 16 weeks, in patients with eosinophilic asthma.

• Drug: Reslizumab
  3.0 mg/kg, administered intravenously (iv) once every 4 weeks over 52 weeks (a total of 13 doses administered)
• Drug: Placebo
  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

• Experimental: Reslizumab
  Intervention: Drug: Reslizumab
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

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.
• 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. Patients' baseline asthma therapy regimen (including but not limited to inhaled corticosteroids, oral steroids up to a maximum of 10 mg of prednisone daily or equivalent, leukotriene antagonists, 5-lipooxegnase inhibitors, cromolyn) must be stable for 30 days prior to screening, and 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 must be willing and able to understand and comply with study restrictions, requirements, and procedures, as specified by the study center, and to remain at the study center for the required duration during the study period, and willing to return to the study center for the follow-up evaluation as specified in the protocol.

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 agents (anti-IgE mAb, methotrexate, cyclosporin, interferon-α, or anti-tumor necrosis factor [anti TNF] mAb) within 6 months prior to screening.
• The patient has participated in an anti-interleukin-5 (IL-5) study for asthma.
• 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] in conjunction with a barrier method) are excluded from this study.
• The patient has concurrent infection or disease that may preclude assessment of active asthma.
• The patient has a history of concurrent immunodeficiency (human immunodeficiency or acquired immunodeficiency syndrome or congenital immunodeficiency).
• The patient has the presence of or suspected parasitic infestation/infection.
• The patient may not have received any live attenuated vaccine within the 12-week period prior to screening.
• The patient has a history of allergic reactions to or hypersensitivity to any component of the study drug.