|E.1 Medical condition or disease under investigation
|E.1.1||Medical condition(s) being investigated ||
|Asthma & elevated blood Eosinophils
|E.1.1.1||Medical condition in easily understood language ||
|E.1.1.2||Therapeutic area ||Diseases [C] - Respiratory Tract Diseases [C08]
|E.1.2 Medical condition or disease under investigation
|E.1.2||Classification code ||10003553
|E.1.2||System Organ Class ||10038738 - Respiratory, thoracic and mediastinal disorders
|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 the ability of reslizumab (110 mg) administered subcutaneously (sc) once every 4 weeks to produce a corticosteroid-sparing effect (as demonstrated by percent reduction in daily OCS use) in patients with OCS-dependent asthma and elevated blood eosinophils, without loss of asthma control.
|E.2.2||Secondary objectives of the trial ||
|The secondary objective of this study is to evaluate the clinical benefits of reslizumab in the context of OCS reduction.
|E.2.3||Trial contains a sub-study || No
|E.3||Principal inclusion criteria ||
|Patients may be included in the study only if they meet all of the
a. The patient is male or female, 12 years of age and older, with a
previous diagnosis of asthma. Patients 12 to <18 years of age are
excluded from participating in South Korea, the Netherlands, and
Argentina, and patients 66 years of age and older are excluded from
participating in South Korea.
b. Written informed consent is obtained. A patient 12 through <18 years
of age must provide assent and his/her parent(s) or legal guardian(s)
must provide consent.
c. The patient continues to require an average daily maintenance dose of
OCS for asthma of between 5 and 40 mg of Prednisone or equivalent
during the 3 months before screening. Patients on an OCS dose of >40
mg at screening who the investigator believes may be able to decrease
OCS dose to ≤40 mg during the optimization period may also be
enrolled. Note: every-other-day dosing that is within this daily average
(ie, 10 to 80 mg) is allowed.
d. The patient has a documented blood eosinophil level of at least
300/μL during the previous 12 months while on at least medium total daily dose of ICS based on Global Initiative for Asthma 2016 clinical
comparability table (Appendix A), or ≥300/μL at screening while on
chronic OCS or that becomes manifest during the OCS optimization
period or at the week -2 visit (end of optimization period/beginning of
e. The patient has required at least 880 μg of inhaled fluticasone
propionate or equivalent daily PLUS another controller(s) (eg, longacting
beta-agonist [LABA], long-acting anti-muscarinic antagonist,
inhibitor, or theophylline), or documented intolerance to
controller, for at least 6 months before the screening visit. For a
ICS/LABA preparation, the highest labeled dose in that region
satisfy this criterion. For patients 12 through <18 years of age, the
dose must correspond to at least a medium total daily ICS dose.
the dose and regimen of asthma controllers and any allergen
should have been stable during the 30 days before
the Informed Assent Form/Informed Consent Form (ICF).
The patient has FEV1 reversibility of at least 12% after administration
inhaled reliever medication according to the standard American
Society (ATS) or European Respiratory Society (ERS) protocol.
the refractory nature of the disease in this population and the
of high background controller medications on reversibility
documented FEV1 reversibility of 12% or a provocation
producing a 20% fall in FEV1 for methacholine of ≤8
within 24 months of the screening visit, and performed
to the standard ATS/ERS procedures, would fulfill this
Patients may be screened again if they did not meet
criteria initially. The duration between the date
Screen Failure and the re-screening must be >30 days.
Females of childbearing potential (not surgically sterile by
bilateral salpingectomy, bilateral oophorectomy or 2
postmenopausal) must have exclusively same-sex partners or use
acceptable methods of birth control and must agree to
use of this method for the duration of the study and for 5
after the last study drug dose. Acceptable methods of birth
include intrauterine device, systemic hormonal contraceptive
implanted, transdermal, or injected), barrier method with
abstinence, bilateral fallopian tube occlusion, and partner
The patient must be willing and able to comply with study restrictions,
and able to perform requisite procedures and to remain at the
for the required duration during the study period, and willing to
to the clinic for the follow up evaluation as specified in this
Except for the OCS, which will be adjusted per protocol, the patient
maintain his/her usual asthma controller regimen without change
the screening, optimization, run-in, and treatment periods.
|E.4||Principal exclusion criteria||
|Patients will be excluded from participating in this study if they meet
any of the following criteria:
a. The patient has any clinically significant, uncontrolled medical
condition (treated or untreated) that would interfere with the study
schedule or procedures and interpretation of efficacy results or would
compromise the patient's safety.
b. The patient has another confounding underlying lung disorder (eg,
chronic obstructive pulmonary disease, interstitial lung disease,
bronchiectasis eosinophilic granulomatosis with polyangiitis [also known
as Churg-Strauss syndrome], or allergic bronchopulmonary
c. The patient has a known hypereosinophilic syndrome.
d. The patient has a history of any malignancy within 5 years of the
screening visit, except for treated and cured non-melanoma skin
e. The patient is pregnant or intends to become pregnant during the
study or within 5 months from last dose of study drug or is lactating. Any
woman becoming pregnant during the study will be withdrawn from the
f. The patient required treatment for an asthma exacerbation within 4
weeks of screening.
g. The patient is a current smoker (ie, has smoked within the last 6
months before screening) or has a smoking history ≥10 pack-years.
h. The patient is currently using any systemic immunosuppressive or
immunomodulatory biologic (eg, anti immunoglobulin E monoclonal
antibody [mAb] or other mAb [eg, mepolizumab] or soluble receptor) or
non-biologic (eg, methotrexate, cyclosporine), except maintenance OCS
for the treatment of asthma. Previous use of such agents that occurred
>5 half-lives from the screening visit may be allowed, if approved by the
i. The patient participated in a clinical study within 30 days or 5 halflives
of the investigational drug before screening, whichever is longer.
j. The patient was previously exposed to benralizumab within 12 months
k. The patient was previously exposed to reslizumab
l. The patient has a history of immunodeficiency disorder including
human immunodeficiency virus.
m. The patient has current suspected drug and/or alcohol abuse.
n. The patient has had an active helminthic parasitic infection or was
treated for one within 6 months of screening.
o. The patient has a history of allergic reactions or hypersensitivity to
any component of the study drug.
p. The patient has a history of latex allergy. (The current prefilled
syringe device has a natural rubber component to the needle shield.)
|E.5 End points
|E.5.1||Primary end point(s)||
|The primary efficacy variable and endpoint for this study is the categorized percent reduction in the daily OCS dose during weeks 20 to 24 as compared with the dose at the end of the optimization phase. Percent reduction will be categorized as follows:
• 90% to 100%
• 75% to <90%
• 50% to <75%
• >0% to <50%
• No decrease in OCS, or loss of baseline asthma control during weeks 20 through 24, or discontinuation from study drug
Loss of baseline asthma control will be defined as FEV1 value of less than 80% of baseline at the week 24 visit, or clinically significant worsening in ACQ-6 score (change in score of 0.5) at the week 24 visit compared with baseline, and/or clinical asthma exacerbation (CAE) during weeks 20 through 24.
|E.5.1.1||Timepoint(s) of evaluation of this end point||
|during the 20-24-week treatment period
|E.5.2||Secondary end point(s)||
|The secondary efficacy endpoints are as follows:
• Proportion of patients achieving ≥50% reduction in OCS dose at weeks 20 to 24 relative to the OCS dose at DoR/baseline, while maintaining asthma control
• Proportion of patients achieving dose reduction to ≤5 mg daily dose at weeks 20 to 24, while maintaining asthma control
• Percent change from DoR/baseline in OCS dose at weeks 20 to 24
• Proportion of patients achieving less than 5 mg decrement in OCS dose (ie, the minimal and non-responders) at weeks 20 to 24 compared with the OCS dose at DoR/baseline, while maintaining asthma control
• Clinical asthma exacerbation related:
- Annualized rate of CAEs requiring a burst of systemic corticosteroid (injection, or if oral, at least a doubling from the current OCS dose for at least 3 days); an asthma-specific hospital admission; or an asthma-specific emergency department visit during the treatment period (weeks 0 to 24)
• Proportion of patients discontinuing OCS at weeks 20 to 24, while maintaining asthma control
|E.5.2.1||Timepoint(s) of evaluation of this end point||
|during the 24-week treatment period.
|E.6 and E.7 Scope of the trial
|E.6||Scope of the trial
|E.6.9||Dose response|| No
|E.6.13.1||Other scope of the trial description||
|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.184.108.40.206||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.8.1.3||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.8.2|| Comparator of controlled trial
|E.8.2.1||Other medicinal product(s)|| No
|E.8.2.2||Placebo || Yes
|E.8.2.4||Number of treatment arms in the trial||2
The trial involves single site in the Member State concerned
|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||2
|E.8.5||The trial involves multiple Member States|| Yes
|E.8.5.1||Number of sites anticipated in the EEA||52
|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||
|Korea, Democratic People's Republic of
|E.8.7||Trial has a data monitoring committee|| No
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|Last Subject Last Visit (LSLV) treatment period is defined as end of treatment (approximately week 24). LSLV late follow up, for immunogenicity testing only, will be performed after the treatment period (approximately week 48). This will be considered the end of the trial for the purposes of end of trial notification.
|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||0
|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||0
|E.8.9.2||In all countries concerned by the trial days||0