None listed
Conditions
Interventions
Fevipiprant (QAW039) 150 mg Type of group
One tablet of QAW039 at 150 mg + one tablet placebo to QAW039 450 mg daily to be given orally during 52 weeks of treatment in addition to the standard of care treatment.
Group name:Fevipiprant (QAW039) Placebo Type of group
One tablet placebo to QAW039 at 450 mg + one tablet placebo to QAW039 150 mg daily to be given orally during 52 weeks of treatment in addition to the standard of care treatment.
Sponsors
NOVARTIS BIOSCIENSES PERU S.A.,
Eligibility
Inclusion criteria
Inclusion criteria: 1. Signed informed consent. 2. Male and female patients ≥18 years 3. Patients with a diagnosis of asthma for a period of at least 3 months prior to Screening Visit with current asthma severity step 4 or 5 (GINA 2018) 4. Currently on treatment with medium or high dose ICS/LABA +/- other controller for a minimum of 6 weeks prior to Screening Visit. 5. At screening, patients with FEV1 of ≤80% of the predicted normal value for the patient, after withholding bronchodilators at Screening Visit and beginning of Run-InVisit . 6. An increase of ≥12% and ≥200 ml in FEV1 approximately 10 to 15 minutes after administration of 400 mcg of salbutamol/albuterol prior to randomization (documented historical reversibility is accepted). 7. Demonstration of inadequate control of asthma based on an ACQ-5 score ≥1.5 at Screening Visit and Treatment Day 1 Visit. 8. Documented history of at least 1 asthma within 1 year prior to enrolment.
Exclusion criteria
Exclusion criteria: 1. Asthma exacerbation, within 6 weeks prior to enrolment that required SCS, hospitalization, or emergency room visit. 2. Chronic/ maintenance use of OCS for asthma. 3. Prior use of biologics. 4. Any contra-indications of SCS use. 5. Pregnant or nursing (lactating) women. 6. Women of child-bearing potential, unless they are using methods of 7. Use of other investigational drugs. 8. Hypersensitivity to any of the study drugs. 9. History of malignancy of any organ system. 10. Patients who have smoked or inhaled any substance other than asthma medications 11. Patients requiring SCS use for conditions other than asthma 12. Patients with a history of chronic lung disease other than asthma,sarcoidosis, interstitial lung disease, cystic fibrosis, and active tuberculosis 13. Patients with history of alcohol or drug abuse 14. Patients with a known history of non-compliance to medication or unable/unwilling to complete an electronic patient diary or Electronic Peak Flow with eDiary device 15. Patients who have had a respiratory tract infection or asthma worsening 16. Patients with any chronic condition of the respiratory tract 17. Patients who have a clinically significant laboratory abnormality 18. Serious co-morbidities 19. Patients receiving any prohibited medication 20. Patients who started immunotherapy or desensitization for allergies 21. Inability to comply with all study requirements and demonstrate good medication compliance 22.Any medical or psychological condition that renders the patient unable to understand the nature, scope, and possible consequences of the study 23. Patients with a history of being unable to swallow tablets 24. Patients who have received immunomodulator or immumomodulatory drugs or any experimental anti-inflammatory therapies 25. Current treatment for hepatic disease 26. History of immunodeficiency disease or hepatitis B or hepatitis C 27. Patients on >20 mg of simvastatin, > 40 mg of atorvastatin, >40 mg of pravastatin, or >2mg of pitavastatin 28. Patients on any statin therapy with a CK level >2 X ULN 29. Patients on rifampin, probenecid, ritonavir and valproic acid 30. No person directly associated with the administration or study site family member is allowed to participate 31. History of lactose or milk sensitivity 32. Conditions other than asthma that could result in elevated eosinophils 33. Diagnosis of ECG abnormalities indicating significant 34. Patients with a resting QTcF (Fridericia) ≥450 msec (male) or ≥460 msec (female) 35. Use of agents with known risk of TdP
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:The primary endpoint will be analyzed in subpopulation of patients with eosinophil count ≥ 250 cells/μl and in overall population using the following primary null hypothesis: • H01 450 eosinophil subgroup: the distribution of the total SoC dose (in mg) in Fevipiprant 450 mg QD plus SoC is equivalent to the distribution of the total SoC dose (in mg) in placebo plus SoC in patients with eosinophil count ≥ 250 cells/μl • H02 150 eosinophil subgroup: the distribution of the total SoC dose (in mg) in Fevipiprant 150 mg QD plus SoC is equivalent to the distribution of the total SoC dose (in mg) in placebo plus SoC in patients with eosinophil count ≥ 250 cells/μl • H03 450 overall population: the distribution of the total SoC dose (in mg)in Fevipiprant 450 mg QD plus SoC is equivalent to the distribution of the total SoC dose (in mg) in placebo plus SoC for the overall population • H04 150 overall population: the distribution of the total SoC dose (in mg)in Fevipiprant 150 mg QD plus SoC is equivalent to the distribution of the total SoC dose (in mg) in placebo plus SoC for the overall population. The total systemic corticosteroid dose in mg prednisone/prednisolone (or equivalent) over 52 weeks of treatment will be analyzed using the Wilcoxon-Mann-Whitney rank sum test (Van Elteren test). For overall population analysis will be stratified byrandomization stratum – blood eosinophils levels (≥ 250 cells/μl and < 250 cells/μl). Measure:Total systemic corticosteroid dose in mg prednisone/prednisolone or equivalent over 52 weeks of treatment. Timepoints:52 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:a) Proportion of patients with free of SCS use over 52 weeks treatment will be summarized by treatment and analyzed using logistic regression in overall population. b) Proportion of patients requiring ≥ 7.5mg systemic corticosteroid dose in mg prednisone/prednisolone (or equivalent) per day continuously for at least 30 days in 52 weeks treatment period will be summarized by treatment and analyzed using logistic regression in overall population. c) AQLQ+12 and ACQ-5 score will be analyzed using a MMRM with an unstructured covariance structure with factors for treatment group, time and randomization stratum, as well as the baseline values as continuous linear covariates. d) Time to first prescription of biologic therapy from first dose of study treatment received over 52 weeks of treatment will be summarized by treatment group. Between-treatment differences will be evaluated using cox regression model. e) Change from baseline in each endpoint (daytime and nighttime symptom score) will be analyzed using mixed models repeated measures (MMRM) model with factors as treatment group, randomization strata, time interval, time interval by treatment group interaction and the associated baseline as continuous linear covariate. f) Safety analysis will be based on safety set and analysis will be presented by treatment group. Safety summaries will be provided based on on-treatment data. Measure:a)Proportion of patients with no SCS use over 52 weeks of treatment. b) Proportion of patients requiring ≥ 7.5mg systemic corticosteroid dose in mg prednisone/prednisolone (or equivalent) per day continuously for at least 30 days c) Asthma Quality of Life Questionnaire (AQLQ+12) and Asthma Control Questionnaire (ACQ-5) d) Time to first prescription of biologic therapy from first dose of study treatment received over 52 weeks of treatment e) Change from baseline in daytime and nighttime symptom scores in 52 weeks of treat | — |
Countries
Argentina, Belgium, Bulgaria, Chile, Colombia, Costa Rica, Czech Republic, France, Germany, Greece, Hungary, Peru, Philippines, Russian Federation, Slovakia, South Africa, Spain, Thailand, Turkey, United Kindgdom, United States, Vietnam
Contacts
Public ContactCecilia Ynouye
NOVARTIS BIOSCIENCES PERU S.A.
Outcome results
None listed