E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment for patients with eosinophilic asthma |
|
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. |
|
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 | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10068462 |
E.1.2 | Term | Eosinophilic asthma |
E.1.2 | System Organ Class | 100000004855 |
|
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.
An exacerbation event will be considered a CAE if the patient meets
either or both of the 2 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
Above criteria must be corroborated with at least 1 other measurement
to indicate worsening in the clinical signs and symptoms of asthma. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of reslizumab treatment compared with placebo
treatment in patients with eosinophilic asthma, as assessed by the effect
of reslizumab on the following:
• overall change from baseline in FEV1 over 16 weeks
• change from baseline in Asthma Quality of Life Questionnaire (AQLQ)
score to week 16
• overall change from baseline in Asthma Control Questionnaire (ACQ)
score over 16 weeks
• time to 1st CAE
• overall change from baseline in Asthma Symptom Utility Index (ASUI)
score over 16 weeks
• overall change from baseline in short-acting beta-agonist use over 16
weeks
• overall change from baseline in blood eosinophil count over 16 weeks
and 52 weeks |
|
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 (a2) is replaced by (a3).
(a2) The patient is 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 Germany, India, Argentina, and Korea; patients 66
through 75 years of age are excluded from participating in India and
Korea.
(b) Inclusion criterion (b) is replaced by (b1).
(b1) The patient has had at least 1 asthma exacerbation requiring oral,
intramuscular, 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/µL.
(d) The patient has airway reversibility of at least 12% to beta-agonist
administration.
(e) Inclusion criterion (e) is replaced by (e1).
(e1) The patient has an ACQ score of at least 1.5 at the screening and baseline (before the 1st dose of study drug) visits.
(f) Inclusion criterion (f2) is replaced by (f3).
(f3) 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 patients' baseline asthma therapy regimen (including but not
limited to inhaled corticosteroids, oral corticosteroids up to a maximum
dose of 10 mg prednisone daily or equivalent, leukotriene antagonists,
5 lipoxygenase inhibitors, cromolyn) must be stable for 30 days prior to
screening and baseline and must continue without dosage changes throughout the 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) Inclusion criterion (h1) is replaced by (h2).
(h2) 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). NOTE: Partner sterility alone is not acceptable for inclusion in the study.
(i) Inclusion criteria (i) is replaced by (i1).
(i1) Written informed consent is obtained. Patients 12 through 17 years
old, where participating, must provide assent.
(j) Inclusion criterion (j) is replaced by (j1).
(j1) 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.
(k) Inclusion criterion (k) is replaced by (k1).
(k1) 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 this protocol.
(l) Patients who experience an asthma exacerbation during the
screening period will be considered to have failed screening and cannot
be randomly assigned to study drug. Patients may be rescreened 1 time
only. |
|
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) Exclusion criterion (e2) is replaced by (e3).
(e3) The patient is using systemic immunosuppressive, 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.
(f) Exclusion criterion (f1) is replaced by (f2).
(f2) The patient has previously received an anti-hIL-5 monoclonal
antibody (eg, reslizumab, mepolizumab, or benralizumab).
(g) Exclusion criterion (g) is replaced by (g1).
(g1) The patient has any aggravating medical factors that are
inadequately controlled (eg, rhinitis, gastroesophageal reflux disease, and uncontrolled diabetes).
(h) Exclusion criterion (h) is replaced by (h1).
(h1) The patient has participated in any investigative drug or device
study within 30 days prior to screening.
(i) Exclusion criterion (i1) is replaced by (i2).
(i2) The patient has participated in any investigative biologics study within 6 months prior to screening.
(j) Exclusion criterion (j1) is replaced by (j2).
(j2) 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.
(k) The patient has concurrent infection or disease that may preclude
assessment of active asthma.
(l) Exclusion criterion (l) is replaced by (l1).
(l1) The patient has a history of concurrent immunodeficiency (human
immunodeficiency virus [HIV] or acquired immunodeficiency syndrome
or congenital immunodeficiency). Patients in Argentina must have
documented serology testing for HIV performed during screening.
(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) Exclusion criterion (n) is replaced by (n1).
(n1) The patient has had an active parasitic infection within 6 months prior to screening.
(o) Patients may not have received any live attenuated vaccine within
the 12-week period prior to screening.
(p) The patient has a history of allergic reactions to or hypersensitivity
to any component of the study drug.
(q) The patient has had an infection requiring the following:
― an admission to the hospital for at least 24 hours within 4 weeks
prior to screening or during the screening period
― treatment with iv antibiotics within 4 weeks prior to screening or
during the screening period
― treatment with oral antibiotics within 4 weeks prior to screening or
during the screening period
(r) The patient has a history of exposure to water borne parasites
within 6 weeks prior to screening or during the screening period or a
history of diarrheal illness of undetermined etiology within 3 months
prior to screening or during the screening period.
(s) The patient requires treatment for an asthma exacerbation within 4
weeks of screening or during the screening period. |
|
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 52 week treatment period. |
|
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. |
|
E.5.2 | Secondary end point(s) |
The secondary efficacy variables and endpoints for this study are as
follows:
• overall change from baseline in FEV1 over 16 weeks
• change from baseline in AQLQ score to week 16
• overall change from baseline in ACQ score over 16 weeks
• time to 1st CAE
• overall change from baseline in ASUI score over 16 weeks
• overall change from baseline in short-acting beta-agonist use over 16
weeks
• overall change from baseline in blood eosinophil count over 16 weeks
and 52 weeks |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | 10 |
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 |
|
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
|
The last visit of the last subject undergoing the trial |
|
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 |