E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Inadequately controlled asthma |
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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 |
The primary objective of this study is to determine the efficacy of LOU064 compared to placebo with respect to change from baseline in pre-dose FEV1 (L) at Week 12. |
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E.2.2 | Secondary objectives of the trial |
- To characterize the pharmacokinetic profile of LOU064 in blood of asthma patients
- To determine the efficacy of LOU064 compared to placebo on changes in morning and evening peak expiratory flow rate (PEF) over the 12-week treatment period
- To determine the efficacy of LOU064 compared to placebo on daytime and nighttime asthma symptom scores over the 12-week treatment period
- To evaluate the safety and tolerability of LOU064 in patients with inadequately controlled Asthma
- To determine the efficacy of LOU064 compared to placebo on change from baseline in Asthma Control Questionnaire-5 (ACQ-5) score over the 12-week treatment period
For detailed list see full protocol
- To determine the efficacy of LOU064 compared to placebo on total daily short-acting β-agonist (SABA) used over the 12-week treatment period |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male and female adult patients aged ≥ 18 to ≤ 70 years at screening
• Patients must weigh at least 40 kg to participate in the study, and must have a body mass index (BMI) <35 kg/m2. BMI = Body weight (kg) / [Height (m)]2 at screening
• Patients with a physician-diagnosed history of asthma (according to GINA (2018)) for a period of at least 6 months prior to screening.
• Patients who have been treated with:
• Medium or high dose ICS, or
• ICS plus long-acting beta agonist (LABA), or
• ICS plus leukotriene receptor antagonist (LTRA), or
• ICS plus long-acting beta agonist (LABA) and long lasting muscarinic antagonist (LAMA) for at least 1 month prior to screening and on the same doses of the above mentioned medications over at least 2 weeks prior to start of the run-in period.
• Post-bronchodilator reversibility of FEV1 ≥ 12% and ≥ 200 mL at screening. If reversibility is not demonstrated at screening, then two additional attempts are permitted (one at the run-in visit and the last one during the run in period between run in visit and baseline visit if needed).
• Spirometry with pre-bronchodilator FEV1 ≥ 40% of predicted (at screening and baseline) and ≤ 85% of predicted at the baseline visit.
• ACQ-5 score ≥ 1.5 at baseline visit
• ≥ 80% compliance with peak expiratory flow measurement and recording of symptoms in the eDiary during the run-in period.
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E.4 | Principal exclusion criteria |
• Patients who have had an asthma exacerbation requiring systemic corticosteroids, hospitalization, or emergency room visit within 6 weeks prior to screening or during the screening period.
• Patients who have smoked or inhaled any substance other than asthma medications within the 6 month period prior to screening, or who have a smoking history of greater than 10 pack years (e.g. 10 pack years = 1 pack/day x 10 years or ½ pack/day x 20 years, etc.).
• History of life-threatening asthma event such as significant hypercarbia (pCO2 > 45 mmHg), endotracheal intubation, non-invasive positive pressure ventilation (NIPPV), respiratory arrest, or seizure as a result of asthma.
• Patients with chronic lung diseases other than asthma, including (but not limited to) chronic obstructive pulmonary disease, clinically significant bronchiectasis, sarcoidosis, interstitial lung disease, cystic fibrosis, Churg-Strauss syndrome, allergic broncho-pulmonary aspergillosis, or clinically significant chronic lung diseases related to a history of tuberculosis or asbestosis.
• At screening and/or run-in period, any severe, progressive or uncontrolled, acute or chronic, medical or psychiatric condition, or other factors such as abnormal vital signs, ECG or physical findings, or clinically relevant abnormal laboratory values, that in the judgment of the investigator may increase the risk associated with study participation/treatment or may interfere with interpretation of study results, and thus would make the patient inappropriate for entry into or continuing the study.
• Major surgery within 8 weeks prior to screening or surgery planned prior to end of study.
• History of live attenuated vaccine within 6 weeks prior to randomization or requirement to receive vaccinations at any time during the study.
• Hematology parameters at screening:
• Hemoglobin: < 10 g/dl
• Platelets: < 100 000/mm3
• White blood cells: < 3 000/mm3
• Neutrophils: < 1 500/mm3
• Significant bleeding risk or coagulation disorders.
• History of gastrointestinal bleeding, e.g. in association with use of Nonsteroidal Anti-Inflammatory Drug (NSAID).
• Requirement for anti-platelet or anticoagulant medication (e.g., warfarin, or clopidogrel or Novel Oral Anti-Coagulant - NOAC) other than acetylsalicylic acid (up to 100 mg/d).
• History or presence of thrombotic or thromboembolic event, or increased risk for thrombotic or thromborembolic event.
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in pre-dose FEV1 at Week 12 |
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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) |
•Concentrations of LOU064 in blood at steady state and calculation of respective PK parameters including but not limited to Cmax, Tmax, AUC0-24h
•Change from baseline in PEF (AM and PM), as assessed by mean morning and mean evening PEF over 12 weeks of treatment (captured in eDiary)
•All safety endpoints (including vital signs, ECG intervals, safety laboratory parameters, adverse events, and serious adverse events) through the End of Study/Early Termination Visit
•Change from baseline in daytime and nighttime asthma symptom score over 12 weeks of treatment (captured in eDiary)
•Change from baseline in ACQ-5 score over 12 weeks of treatment (ACQ-assessment for the week preceding each planned visit up to End of Study)
•Number of puffs of SABA taken per day over 12 weeks of treatment (captured in eDiary)
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
Other biomarkers assessment |
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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) | 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 | 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
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 |
China |
Germany |
Poland |
Russian Federation |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 12 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |