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 | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10068462 |
E.1.2 | Term | Eosinophilic asthma |
E.1.2 | System Organ Class | 100000004855 |
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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 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). |
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E.2.2 | Secondary objectives of the trial |
• to evaluate the efficacy of reslizumab :
― lung function as measured by FEV1, % predicted FEV1, FVC and FEF25-75%
― Short-acting beta-agonist use
― blood eosinophil count
― asthma symptoms (ASUI)
― asthma control (ACQ)
― quality of life (AQLQ)
• to characterize the PK of reslizumab
• to characterize the relationship between serum concentrations of reslizumab and measures of efficacy and safety
• to evaluate the safety and tolerability of reslizumab:
― occurrence of adverse events
― clinical laboratory test results
― vital signs measurements
― physical examination findings
― 12-lead electrocardiography (ECG) findings at week 16 or early withdrawal
― concomitant medication usage
― to assess immunogenicity by measurement of anti-reslizumab antibodies at baseline and at weeks 8 and 16 or early withdrawal |
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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) Inclusion criterion (a) is replaced by (a1).
(a1) The patient is a 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 India and Argentina; patients 66 through 75 years of age are excluded from participating in India.
(b) The patient has an ACQ score of at least 1.5.
(c) The patient has airway reversibility of at least 12% to beta-agonist administration at screening.
(d) Inclusion criteria (d ) is replaced by (d1).
(d1) The patient is currently taking fluticasone at a dosage of at least 440 μg daily (or equivalent). Patients’ baseline asthma therapy regimen (including but not limited to inhaled corticosteroids, leukotriene antagonists, 5-lipooxegnase inhibitors, cromolyn) must be stable for 30 days before screening, and continue without dosage changes throughout the study.
(e) The patient has a blood eosinophil count of at least 400/L.
(f) Female patients must be surgically sterile, 2 years postmenopausal, or must have a negative pregnancy test beta-human chorionic gonadotropin (ßHCG) at screening (serum) and baseline (urine).
(g) Inclusion criterion (g) is replaced by (g1).
(g1) 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).
(h) Inclusion criterion (h) is replaced by (h1).
(h1) Written informed consent is obtained. Patients 12 through 17 years old, where participating, need to provide assent in accordance with local standards.
(i) 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, urinalysis, and serology.
(j) 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 HES.
(c) Exclusion criteria (c) is replaced by (c1).
(c1) 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 aspergilosis).
(d) The patient is a current smoker (ie, has smoked within the last 6 months prior to screening).
(e) 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 (randomization).
(f) The patient is currently using systemic corticosteroids (includes use of oral corticosteroids).
(g) The patient is expected to be poorly compliant with study drug administration, study procedures, or visits.
(h) The patient has any aggravating factors that are inadequately controlled (eg, gastroesophageal reflux disease).
(i) The patient has participated in any investigative drug or device study within 30 days prior to screening.
(j) The patient has participated in any investigative biologics study within 90 days prior to screening.
(k) The patient has previously received anti-hIL-5 monoclonal antibody (eg, mepolizumab).
(l) Exclusion criterion (l) is replaced by (l1).
(l1) Female patients who are pregnant, or nursing, or, if of childbearing potential and not using a medically accepted, effective method of birth control (eg, spermicide, abstinence, IUD, or steroidal contraceptive [oral, transdermal, implanted, and injected]) are excluded from this study.
(m) The patient has a current infection or disease that may preclude assessment of asthma.
(n) Exclusion criterion (n) is replaced by (n1)
(n1) 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.
(o) The patient has current suspected drug or alcohol abuse as specified in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria.
(p) The patient has presence of or suspected parasitic infestation/infection.
(q) Patients may not have received any live attenuated vaccine within the 12-week period before screening.
(r) The patient has a history of allergic reactions to or hypersensitivity to any component of the study drug. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable for this study is the change from baseline in FEV1.
FEV1 is a standard measurement of air movement in the lungs of patients with asthma. It is the volume of air expired in the first second of a forced expiration. Improvement in FEV1 is a measure of the reduction of bronchospasm, the reduction of airway inflammation, or both. FEV1 will be measured using forced expiratory air spirometry. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Week 4, 8, 12, 16 or early withdrawal |
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E.5.2 | Secondary end point(s) |
The secondary efficacy measures and endpoints for this study are as follows:
• Lung function as measured by FEV1, % predicted FEV1, FVC, and FEF25-75% at weeks 4, 8, 12, 16, or early withdrawal
• Short-acting beta-agonist use at weeks 4, 8, 12, 16, or early withdrawal
• blood eosinophil count at weeks 4, 8, 12, 16, and follow-up or early withdrawal
• ASUI at weeks 4, 8, 12, 16, or early withdrawal
• ACQ at weeks 4, 8, 12, 16, or early withdrawal
• AQLQ at week 16, or early withdrawal
Exploratory variables and endpoints for this study are as follows:
• sputum eosinophil levels measured at baseline and week 16 or early withdrawal (subset of patients only)
• biomarkers measured at screening, baseline, and at weeks 8 and 16, or early withdrawal |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
• Lung function as measured by %FEV1, % predicted FEV1, FVC, and FEF25-75% at weeks 4, 8, 12, 16 or early withdrawal
• Short-acting beta-agonist use assessed at weeks 4, 8, 12, 16, or early withdrawal
• Blood eosinophil count measured at weeks 4, 8, 12, 16, and follow-up or early withdrawal
• ASUI at weeks 4, 8, 12, 16, or early withdrawal
• ACQ at weeks 4, 8, 12, 16, or early withdrawal
• AQLQ at week 16, or early withdrawal
Exploratory variables and endpoints for this study are as follows:
• Sputum eosinophil levels measured at at baseline and week 16 or early withdrawal
• Biomarkers measured at screening, baseline, and at weeks 8 and 16, or early withdrawal |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | 3 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 21 |
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 |
Belgium |
Brazil |
Canada |
Colombia |
Hungary |
Netherlands |
Sweden |
Israel |
Mexico |
Poland |
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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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 | 0 |
E.8.9.1 | In the Member State concerned months | 24 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 30 |
E.8.9.2 | In all countries concerned by the trial days | 0 |