E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 20.0 |
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 |
To evaluate the effects of SAR440340/REGN3500 with or without dupilumab, compared to placebo, on reducing the incidence of “loss of asthma control” (LOAC) events. |
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E.2.2 | Secondary objectives of the trial |
-To evaluate the effects of SAR440340/REGN3500 and coadministration of SAR440340/REGN3500 and dupilumab, compared with placebo, on forced expiratory volume in 1 second (FEV1).
-To evaluate the effects of coadministration of SAR440340/REGN3500 and dupilumab, compared with SAR440340 and compared with dupilumab, on FEV1.
-To assess safety and tolerability of SAR440340/REGN3500 alone and in coadministration with dupilumab. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Adult patients with a physician diagnosis of asthma for at least 12 months based on the Global Initiative for Asthma (GINA) 2017 Guidelines.
-Patients with existing treatment with medium to high dose ICS (≥250 mcg of fluticasone propionate BID or equipotent ICS daily dosage to a maximum of 2000 mcg/day of fluticasone propionate or clinically comparable) in combination with a LABA as second controller for at least 3 months with a
stable dose ≥1 month prior to Visit 1.
-Patients with prebronchodilator forced expiratory volume (FEV1) >40% of predicted normal at Visit 1/Screening. Pre-bronchodilator FEV1 ≥50% but ≤85% of predicted normal at Visit 2/Baseline.
-Patients with reversibility of at least 12% and 200 mL in FEV1 after administration of 2 to 4 puffs (200-400 mcg) of albuterol/salbutamol or levalbuterol/levosalbutamol during screening or documented history of a reversibility test that meets this criteria within 12 months prior to Visit 1 or
documented positive response to methacholine challenge (a decrease in FEV by 20% [PC20] of <8mg/mL) within 12 months prior to Visit 1/Screening is considered acceptable to meet this inclusion criterion.
-Patients must have experienced, within 1 year prior to Visit 1, any of the following events at least once:
-Treatment with a systemic steroid (oral or parenteral) for worsening asthma;
-Hospitalization or emergency medical care visit for worsening asthma.
-Signed written informed consent. |
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E.4 | Principal exclusion criteria |
-Patients <18 years or >70 years of age (i.e., have reached the age of 71 at the screening visit).
-Patients with body mass index (BMI) <16.
-Chronic lung disease (for example, chronic obstructive pulmonary disease [COPD], or idiopathic pulmonary fibrosis [IPF]), which may impair lung function.
-History of life threatening asthma (i.e., severe exacerbation that requires intubation).
-Co-morbid disease that might interfere with the evaluation of IMP.
-Patients with any of the following events within the 4 weeks prior to their Screening Visit 1:
-Treatment with 1 or more systemic (oral and/or parenteral) steroid bursts for worsening asthma;
-Hospitalization or emergency medical care visit for worsening asthma.
-Asthma Control Questionnaire 5-question version (ACQ-5) score <1.25 or >3.0 at V2/randomization. During the screening period, an ACQ-5 of up to ≤4 is acceptable.
-Anti-immunoglobulin E (IgE) therapy (e.g., omalizumab [Xolair®]) within 130 days prior to Visit 1 or any other biologic therapy (including anti-IL5 mAb) or systemic immunosuppressant (e.g., methotrexate) to treat inflammatory disease or autoimmune disease (e.g., rheumatoid arthritis, inflammatory bowel disease, primary biliary cirrhosis, systemic lupus erythematosus, multiple sclerosis, etc.) and other diseases, within 2 months or 5 half-lives prior to Visit 1, whichever is longer.
-Patients with a history of a systemic hypersensitivity reaction to a biologic drug.
-Patients on or initiation of bronchial thermoplasty within 2 years prior to Visit 1 or plan to begin therapy during the screening period or the randomized treatment period.
-Current smoker or cessation of smoking within the 6 months prior to Visit 1.
-Previous smoker with a smoking history >10 pack-years. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Loss of asthma control (LOAC) events: Proportion of patients with LOAC |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Change in forced expiratory volume in 1 second (FEV1): FEV1 change from baseline at Week 12 (pre- and post-bronchodilator) |
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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 | No |
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 | No |
E.6.10 | Pharmacogenetic | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | 4 |
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 | 8 |
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 |
Chile |
Mexico |
Poland |
Russian Federation |
Turkey |
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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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |