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 assess the change from baseline in sputum eosinophil levels after 12 weeks of treatment with fevipiprant compared to placebo in asthma patients with sputum eosinophilia |
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E.2.2 | Secondary objectives of the trial |
To assess safety and tolerability of fevipiprant compared to placebo in asthma patients with sputum eosinophilia |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All Subjects (Asthma patients, Healthy volunteers): 1. Written informed consent must be obtained before any assessment is performed. 2. Male and female subjects aged ≥ 18 years at screening 3. Able to communicate well with the investigator, to understand and comply with the requirements of the study.
Moderate-to-severe asthma patients (Asthma patients): 1. Patients with a diagnosis of asthma currently treated with at least medium dose of ICS, alone or with any other asthma controller therapy, except those listed as prohibited medications. Patients must be on stable doses of asthma medications for at least 4 weeks prior to screening. 2. A clinical diagnosis of asthma supported by at least one of the following within five years prior to screening : - Reversible airway obstruction defined as an increase of ≥ 12% and ≥ 200 ml in FEV1 or FVC over the patient’s pre-bronchodilator value within 30 minutes after inhaling a total of 360 μg of albuterol or 400 μg salbutamol via metered dose inhaler (reversibility test). - A positive airway hyper-reactivity (AHR) test result defined as a provoked fall in FEV1 of 20% (PC20) by methacholine at ≤ 8 mg/ml when not on ICS or ≤ 16 mg/ml on ICS therapy. - A change in FEV1 of ≥ 12% over two measurements within 12 months. 3. ACQ7 score ≥ 1.25 at screening and baseline visits, which may be repeated once at each visit. 4. Demonstrate ability to produce a good quality induced-sputum sample at baseline visits. Note: Sputum induction test may be repeated once at each applicable visit. 5. Sputum eosinophil count ≥ 2% at visit 20 and blood eosinophil count ≥ 250 cells/μL at screening (visit 1) and baseline visit (visit 30). Note: Re-testing is allowed once to qualify patient at that visit.
Healthy volunteers (Healthy volunteers): 1. Subject must be in good health as determined by past medical history, current medications, physical examination, vital signs, electrocardiogram, and laboratory tests at screening. Note: Subjects with well-controlled, mild, non-respiratory diseases can participate as long as they are considered healthy and stable in the investigator's judgement. |
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E.4 | Principal exclusion criteria |
All Subjects (Asthma patients, Healthy volunteers): 1. Use of other investigational drugs at the time of screening, or within 5 half-lives of experimental drug at the time of screening, or within 30 days of last dose of experimental drug at the time of screening, whichever is longer; or longer if required by local regulations. 2. Cirrhosis, hepatic failure, chronic infection with Hepatitis B (HBV) or Hepatitis C (HCV). At screening, a positive HBV surface antigen (HBsAg) test, or if standard local practice, a positive HBV core antigen test, excludes a subject. Subjects with a positive HCV antibody test should have HCV RNA levels measured. Subjects with positive (detectable) HCV RNA should be excluded. 3. At screening, a positive HIV test or is taking anti-retroviral medications, as determined by medical history and/or subject’s verbal report. 4. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in-situ cervical cancer), treated or untreated, within 5 years of screening, regardless of whether there is evidence of local recurrence or metastases. 5. Donation or loss of 450 mL or more of blood within eight weeks prior to screening visit or longer if required by local regulation. 6. Plasma donation (>150 mL) within 30 days prior to screening visit. 7. History of drug or alcohol abuse within the 12 months prior to screening visit. 8. Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless using basic methods of contraception 9. At screening, pregnant or nursing (lactating) women. 10. History of parasitic infestation within 6 months prior to screening Moderate-to-severe asthma patients (Asthma patients): 1. Patients with a current or past medical history of conditions other than asthma or allergic rhinitis that could result in elevated blood or sputum eosinophils (e.g., hypereosinophilic syndrome, chronic eosinophilic pneumonia, Churg-Strauss Syndrome). 2. History of hypersensitivity to any of the study treatments or excipients or to drugs of similar chemical classes 3. Patients with history of concomitant chronic or severe pulmonary disease other than asthma (e.g., COPD, bronchiectasis, sarcoidosis, interstitial lung disease, cystic fibrosis, active tuberculosis). 4. Patients on statin therapy with a CK level >2 X ULN at screening. 5. Patients on prohibited treatment listed in Table 6-2. 6. Patients who have had an asthma exacerbation requiring systemic corticosteroids, hospitalization, or emergency room visit within 4 weeks prior to and/or during screening or baseline. 7. Patients who have had a respiratory tract infection or asthma worsening within 4 weeks of screening. 8. Subjects who have smoked or inhaled any foreign substance (marijuana, etc.) other than asthma medications within the 4 week period prior to screening, or who have a cigarette smoking history of greater than 10 pack years (Note: 10 pack years = 1 pack/day during 10 yrs., or ½ pack/day during 20 yrs.). 9. Patients with a history of myocardial infarction within 12 months of screening. 10. History or current diagnosis of ECG abnormalities indicating significant risk of safety 11. Any severe, progressive or uncontrolled, acute or chronic, medical or psychiatric condition 12. Patients who have a clinically significant laboratory abnormality at screening or baseline visit 13. Use of biologic therapy for asthma (e.g. omalizumab, mepolizumab, benralizumab, dupilumab) within 3 months or 5 half-lives prior to screening, whichever is longer. 14. Use of immunosuppressive medication within 4 weeks prior to screening. Inhaled and topical glucocorticoids and low dose (≤15mg prednisolone/day) oral corticosteroids are permitted. Healthy volunteers (Healthy volunteers): 1. History of allergies or atopy (e.g., allergic rhinitis, urticaria, eczematous dermatitis). 2. Recent (within three years of screening) and/or recurrent history of acute or chronic obstructive disease (including asthma and chronic obstructive pulmonary disease, treated or not treated). 3. Use of any prescription drugs, herbal supplements, prescribed medicinal use of cannabis/marijuana, within four weeks prior to screening assessments, and/or (OTC) medication, dietary supplements (vitamins included) within two weeks prior to screening. 4. Significant illness, which has not resolved within two weeks prior to screening. 5. Patients who have smoked or inhaled any foreign substance (nicotine, marijuana, etc.) within the 4 week period prior to screening, or who have a cigarette smoking history of greater than 10 pack years (Note: 10 pack years = 1 pack/day during 10 yrs., or ½ pack/day during 20 yrs.). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Sputum eosinophil % of total cell count on Day 84 |
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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) |
Vital signs, ECG parameters, clinical safety laboratory parameters (chemistry/hematology/urinalysis), (serious) adverse events |
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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 | Yes |
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 | Yes |
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 | 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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 22 |
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 | 8 |
E.8.9.1 | In the Member State concerned days | |
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 | 8 |