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 | 19.0 |
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 investigate whether airway hyperresponsiveness to mannitol decreases in response to treatment with MEDI9929 in patients with asthma |
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E.2.2 | Secondary objectives of the trial |
To evaluate if a reduced AHR to mannitol following treatment with MEDI9929 is related to a reduction in chymase/CPA-3 positive mast cells.
To investigate changes in airway eosinophils and neutrophils in patients treated with MEDI9929 compared to placebo.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Written informed consent 2. Age 18 through 75, inclusive at the time of Visit 1 3. Body mass index between 18-40 kg/m2 (both inclusive) and weight ≥ 40 kg at Visit 1. 4. A diagnosis of asthma as defined by GINA (ginasthma.org). 5. ICS (in any dose) on a daily basis for at least three months prior to Visit 1 6. A stable asthma controller regimen with ICS (±LABA) for at least 4 weeks prior to Visit 1 7. A FEV1 value of ≥ 70% at Visit 1 8. ACQ-6 > 1 (partly controlled) at Visit 1 9. PD15 to mannitol <= 315 mg at visit 1
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E.4 | Principal exclusion criteria |
1. Current smokers or subjects with a smoking history of ≥ 10 pack years. Former smokers with < 10 pack years must have stopped for at least 6 months to be eligible. 2. Previous medical history or evidence of an uncontrolled intercurrent illness. 3. Any clinically relevant abnormal findings in hematology or clinical chemistry. 4. Evidence of active liver disease. 5. History of cancer. 6. Acute upper or lower respiratory infections requiring antibiotics or antiviral medications within 15 days prior to Visit 1. 7. A helminth parasitic infection diagnosed within 24 weeks of Visit 1. 8. Known history of active tuberculosis (TB). 9. Positive hepatitis B surface antigen, or hepatitis C virus antibody serology at screening. 10. Oral corticosteroids (any dose for more than 3 days) 12 weeks prior to Visit 1 or during the run-in period. 11. Pregnant, breastfeeding or lactating females. 12. Concomitant respiratory disease |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in PD15 to mannitol (provoking dose for 15% reduction in FEV1) from V1 to V6 (ΔPD15 (V6-V1) placebo vs. ΔPD15 (V6-V1) MEDI9929) (in doubling doses)
Supportive primary objectives: • The change in PD15 to mannitol, expressed as geometric mean calculated by linear interpolation, from baseline (V1) to week 12 (V6) will be compared between treatments. Subjects who are no longer positive to mannitol (PD15>635 mg) after 12 weeks of treatment will be evaluated as having a PD15 of 635mg in the analysis. • Number of mannitol test negative (PD15 > 635mg) subjects at V6 between groups • Change in RDR (Response Dose Ratio) to mannitol measured at V1 and V6 between groups |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Expected end of trial is Dec 2017. |
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E.5.2 | Secondary end point(s) |
Cell count in airway submucosa, airway epithelium and airway smooth muscle measured at V2 and V7: - MCT, MCTC and MCCPA3 - Number / percentage of eosinophils and neutrophils in airway submucosa, sputum and blood. - Level of FeNO.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Expected end of trial is Dec 2017. |
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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 | 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) | 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 | 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 | 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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |