E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment for patients with eosinophilic asthma |
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E.1.1.1 | Medical condition in easily understood language |
A particular form of asthma characterized by the presence of a high number in the lungs of a certain type of white blood cells, called eosinophils, which lead to airways inflammation and symptoms. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10068462 |
E.1.2 | Term | Eosinophilic asthma |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to determine whether reslizumab, at a dose of 3 mg/kg administered intravenously (iv) every 4 weeks over 12 months, is more effective than placebo in reducing the number of clinical asthma exacerbations (CAEs) in patients with eosinophilic asthma as assessed by the frequency of CAEs. A CAE is defined by one of the following: 1) a hospitalization because of asthma, 2) emergency treatment because of asthma, 3) a decrease in forced expiratory volume in 1 second (FEV1) by 20% or more, or 4) a decrease in peak expiratory flow rate (PEFR) of 30% or more in 2 consecutive measurements. Emergency treatment includes unscheduled visits to the physician’s office for nebulizer treatment or other urgent treatment to prevent worsening of asthma symptoms, or a visit to the emergency room for treatment, regardless of subsequent admission. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are the following: • to evaluate the efficacy of reslizumab: ― lung function [FEV1], [%FEV1], [FVC], [FEF25-75%] ― time to first CAE ― oral corticosteroids prescribed for asthma worsening ― use of short-acting beta-agonists ― blood eosinophil count ― Asthma Symptom Utility Index (ASUI) ― Asthma Control Questionnaire (ACQ) ― Asthma Quality of Life (AQLQ) • to evaluate the safety and tolerability of reslizumab: ― occurrence of adverse events ― clinical laboratory test results ― vital signs ― ECG findings ― physical examination findings ― concomitant medication usage throughout the study ― measurement of anti-drug antibodies • as exploratory objectives, to evaluate PEFR, and to characterize potential biomarkers in sputum that may more effectively identify patients who have this phenotype of asthma |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients are included in the study if all of the following criteria are met: (a) The patient is male or female, 12 through 75 years of age, with a previous diagnosis of asthma. (b) The patient has had at least 1 asthma exacerbation requiring oral or iv corticosteroid use for at least 3 days over the past 12 months before screening. (c) The patient has a current blood eosinophil level of at least 400/L. (d) The patient has airway reversibility of at least 12% to beta-agonist administration. (e) The patient has an ACQ score of at least 1.5. (f) Inclusion criterion (f) is replaced by (f1). 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, leukotriene antagonists, 5-lipooxegnase inhibitors, cromolyn) must be stable for 30 days prior to screening, and continue without dosage changes throughout study. (g) 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). (h) 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. Acceptable methods of contraception include barrier method with spermicide, abstinence, intrauterine device (IUD), or steroidal contraceptive (oral, transdermal, implanted, and injected) in conjunction with a barrier method. (i) Written informed consent is obtained. Patients 12 through 17 years old must provide assent. (j) 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, serum chemistry, hematology, and urinalysis. (k) The patient must be willing and able to comply with study restrictions and to remain at the clinic for the required duration during the study period, and willing to return to the clinic for the follow-up evaluation as specified in this protocol. |
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E.4 | Principal exclusion criteria |
Patients are excluded from participating in this study if 1 or more of the following criteria are met: (a) The patient has a clinically meaningful comorbidity that would interfere with the study schedule or procedures, or compromise the patient’s safety. (b) The patient has known hypereosinophilic syndrome. (c) Exclusion criterion (c) is replaced by (c1). 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. (d) The patient is a current smoker (ie, has smoked within the last 6 months prior to screening). (e) The patient is using systemic immunosuppressive or immunomodulating drugs eg, systemic corticosteroids greater than 10 mg/day daily dose, methotrexate, cyclosporine, antibody 6 months prior to study entry (randomization). (f) The patient has participated in an anti-interleukin-5 (IL-5) study for asthma. (g) The patient has any aggravating medical factors that are inadequately controlled (eg, rhinitis, gastroesophageal reflux disease). (h) The patient has participated in any investigative drug or device study within 30 days prior to study enrollment (randomization). (i) The patient has participated in any investigative biologics study within 3 months prior to study enrollment (randomization). (j) 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. (k) The patient has concurrent infection or disease that may preclude assessment of active asthma. (l) The patient has a history of concurrent immunodeficiency (human immunodeficiency or acquired immunodeficiency syndrome or congenital immunodeficiency). (m) The patient has current suspected drug and alcohol abuse as specified in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria. (n) Presence of or suspected parasitic infestation /infection. (o) Patients may not have received any live attenuated vaccine within the 12-week period prior to screening. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy measure for this study is the frequency of CAEs per patient during the double-blind treatment period and within 2 weeks after the last visit.
A CAE is defined by 1 of the following: 1) a hospitalization because of asthma, 2) emergency treatment because of asthma, 3) a decrease in FEV1 by 20% or more, or 4) a PEFR of 30% or more in 2 consecutive measurements.
Patients who experience a CAE will be instructed to come to the study center for pulmonary function tests and asthma symptom score assessment. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The frequency of CAEs per patient will be measured during the 52 week double-blind treatment period and within 2 weeks after the last visit.
A CAE is defined by 1 of the following: 1) A hospitalization because of asthma, 2) Emergency treatment because of asthma, 3) A decrease in FEV1 by 20% or more, or 4) A PEFR of 30% or more in 2 consecutive measurements.
Patients who experience a CAE will be instructed to come to the study center for pulmonary function tests and asthma symptom score assessment. |
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E.5.2 | Secondary end point(s) |
The secondary efficacy variables and endpoints for this study are as follows:
• Change in lung function as measured by FEV1, %FEV1, FVC, FEF25-75% from baseline to weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52, and endpoint, or at time of first CAE • Time to first CAE • Change in the number of courses of oral corticosteroids prescribed for asthma worsening (3 or more days of administration or doubling of current dose) from baseline to weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52, and endpoint, or at time of first CAE • Change in short-acting beta-agonist use from baseline to weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52, and endpoint, or at time of first CAE • Change in blood eosinophil count from baseline to weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52, and endpoint, or at time of first CAE • Change in ASUI score at weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52, and endpoint, or at time of first CAE • Change in ACQ score from baseline to weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52, and endpoint, or at time of first CAE • Change in AQLQ score from baseline to weeks 16, 32, and 52, and endpoint, or at time of first CAE |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 37 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Brazil |
Canada |
France |
Germany |
Greece |
India |
Korea, Republic of |
Mexico |
Peru |
Romania |
Russian Federation |
Slovakia |
Taiwan |
Ukraine |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The last visit of the last subject undergoing the trial |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |