E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Uncontrolled Asthma & elevated blood Eosinophils |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003553 |
E.1.2 | Term | 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 support the long-term safety of reslizumab 110 mg administered sc once every 4 weeks in patients 12 years of age and older with severe eosinophilic asthma whose asthma is inadequately controlled on standard-of-care treatment. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective of this study is to evaluate the efficacy of reslizumab 110 mg administered sc once every 4 weeks in patients 12 years of age and older with severe eosinophilic asthma that is inadequately controlled on standard-of-care treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients may only be included in the study if they meet all of the following criteria:
a. Written informed consent is obtained. A patient 12 through <18 years of age must provide assent, and their parent(s) or legal guardian(s) must provide consent.
b. Male or female patient 12 years or older with eosinophilic asthma who was previously randomized and completed the treatment period in either of the double-blind, placebocontrolled studies (Study 30025 or 30027) for sc reslizumab and who by the assessment of the Principal Investigator can safely participate in this study.
Adolescents from Study 30025 must also complete the early follow-up visit before being eligible for this study.
c. Unless surgically sterile or postmenopausal, female patients must have a negative urine pregnancy test at baseline. Definitions of sterile and postmenopausal are given in Protocol Appendix E.
d. Females of childbearing potential (not surgically sterile or postmenopausal) must have an exclusively same-sex partner or use a medically acceptable method of contraception and must agree to continue the use of this method for the duration of the study and for 5 months after discontinuation of the study drug. Acceptable methods of contraception include intrauterine device, steroidal contraceptive (oral, implanted, transdermal, or injected), barrier method with spermicide, abstinence, bilateral tubal occlusion, and partner vasectomy.
e. The patient must be willing and able to comply with study restrictions and willing to return to the investigational center for the follow-up procedures and assessments as specified in this protocol. |
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E.4 | Principal exclusion criteria |
Patients will be excluded from participating in this study if they meet any of the following criteria:
a. Patient has received any intravenous or sc reslizumab administration in any previous clinical trial other than Studies 30025 and 30027.
b. Patient withdrew early (discontinued from treatment) from either of the placebocontrolled reslizumab studies, Studies 30025 and 30027, for any reason.
c. 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.
d. 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
aspergillosis).
e. The patient has a known/diagnosed hypereosinophilic syndrome.
f. The patient has a diagnosis of malignancy within 5 years of the screening visit, except for treated and cured non-melanoma skin cancers.
g. The patient is a pregnant or lactating woman or intends to become pregnant during the study or within 5 months after the last dose of study drug. Administration of IMP will be discontinued for any female patient who becomes pregnant during the study.
h. The patient required treatment for an asthma exacerbation within 4 weeks of screening or during the screening. (Note: This is required only in patients who did not rollover seamlessly from Study 30025 or 30027, ie, had a gap between placebo-controlled study
EOT and screening for Study 30066 [including adolescents from Study 30025 who must also complete the early follow-up visit].)
Patients who did not rollover seamlessly from Study 30025 or 30027 may be considered for rescreening if they are excluded from study participation for not satisfying this criterion. A patient may be rescreened for this reason 1 time only. The duration between
the first visit during the screening period and the rescreening must be >30 days.
i. The patient is a current smoker (ie, has smoked within the last 6 months before screening) or has a smoking history ≥10 pack-years.
j. The patient is currently using any systemic immunosuppressive or immunomodulatory biologic (eg, anti-immunoglobulin E monoclonal antibody [mAb] or other mAb [eg, mepolizumab, benralizumab, dupilumab] or soluble receptors) or non-biologic (eg, methotrexate or cyclosporine), except maintenance oral corticosteroids for the treatment of asthma (up to and including 40 mg of prednisone daily or equivalent every-other-day dosing). Note: Previous use of such agents that occurred >5 half-lives from the initial screening visit may be allowed.
k. The patient participated in a clinical study other than approved Teva reslizumab studies within 30 days or 5 half-lives of the investigational drug before screening, whichever is longer.
l. The patient has a history of an immunodeficiency disorder including human immunodeficiency virus (HIV).
m. The patient has current or suspected drug and/or alcohol abuse.
n. The patient has an active helminthic parasitic infection or was treated for one within 6 months of screening.
o. The patient has a history of allergic reaction or hypersensitivity to any component of the study drug.
p. The patient is expected to be poorly compliant with study procedures or visits.
q. The patient is a vulnerable patient (eg, a patient who is or may be for any reason unable to take care of himself or herself, unable to protect himself or herself against significant harm or exploitation, or kept in detention). |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the frequency of adverse events including serious adverse events. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Patient counts and percentages will be provided for the frequency of patients with at least 1 adverse event. |
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E.5.2 | Secondary end point(s) |
The secondary safety endpoints for this study include the following:
- clinical laboratory test results
- hematology and chemistry results at baseline and at weeks 4 (chemistry only), 8, 24, and 36 or early withdrawal visit
- local tolerability at the injection site at approximately 1 hour after study drug administration every 4 weeks throughout the study
- vital signs measurements every 4 weeks throughout the study
- concomitant medication usage every 4 weeks throughout the study
The secondary efficacy endpoints for this study include the following:
- clinical asthma exacerbation (CAE) and healthcare utilization (HCU)-related endpoints
- frequency of CAEs
- frequency of asthma-specific hospital admissions
- length of hospital stay and number of ICU days
- frequency of asthma-specific emergency department visits
- frequency of school/work days missed due to asthma
- change from baseline in pre-bronchodilator FEV1 measured using spirometry at weeks 0, 8, 24, and 36 or early withdrawal visit
- change in daily morning ambulatory FEV1 from baseline at each week through week 36 or early withdrawal, as measured by the handheld spirometry device
- absolute and percent reduction in the daily OCS dose at weeks 20 and 36 or early withdrawal visit as compared with the dose at baseline (for patients on daily OCS at baseline)
- change from baseline in total inhalations of reliever bronchodilator medication (eg, short-acting beta-agonist) measured using weekly averages until week 36 or early withdrawal visit
- change from baseline in ACQ-6 score performed at weeks 0, 8, 24, and 36 or early withdrawal visit
- change from baseline in AQLQ12+ score performed at weeks 0, 8, 24, and 36 or early withdrawal visit |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary safety endpoints include clinical laboratory tests, local site reactions, vital signs measurements, and concomitant medication usage. Secondary efficacy endpoints include CAE and HCU-related events, change from baseline in pulmonary function tests, absolute and percent reduction in the daily OCS dose (for patients on daily OCS at baseline), change from baseline in total inhalations of reliever bronchodilator medication (eg, SABA), and change from baseline in patient-reported outcome questionnaires (ACQ-6 and AQLQ12+).
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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 | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
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 | 91 |
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 |
Belgium |
Canada |
Czech Republic |
France |
Germany |
Hungary |
Israel |
Poland |
Romania |
Russian Federation |
Spain |
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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Last Patient Last Visit (LPLV) of the treatment period is defined as the EOT. The EOS visit for immunogenicity testing only will be performed 19 weeks (±2 weeks) after the final dose of study drug (approximately week 51). This will be considered the end of the trial for the purposes of end of trial notification |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | |
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 |