A study to evaluate the efficacy and safety of three doses of frevecitinib in patients with severe asthma not adequately controlled with medium to high dose ICS/LABA therapy

INTERVENTION: Product Name: KN‐002, Product Code:PRD13844786, Pharmaceutical Form: INHALATION POWDER, HARD CAPSULE, Other descriptive name: , Strength: , Product Name: KN‐002 (frevecitinib) Placebo Inhalation Powder (excipients only), Product Code:N/A, Pharmaceutical Form: N/A, Other descriptive name: N/A , Strength: , Pharmaceutical form of the placebo: N/A , Product Name: , Product Code:SCP111080421, Pharmaceutical Form: , Other descriptive name: , Strength: , Product Name: KN‐002, Product Code:PRD13844785, Pharmaceutical Form: INHALATION POWDER, HARD CAPSULE, Other descriptive name: , Strength: CONDITION: Severe asthma ; MedDRA version: 20.0Level: PTClassification code: 10003553Term: Asthma Class: 100000004855 Therapeutic area: Diseases [C] ‐ Respiratory Tract Diseases [C08] PRIMARY OUTCOME: Main Objective: To evaluate the clinical efficacy of frevecitinib Primary end point(s): Change in predose (pre‐bronchodilator) FEV1 (L) from baseline to Week 12 Secondary Objective: 1. To evaluate the clinical safety and tolerability of frevecitinib, 2. To evaluate the clinical efficacy of frevecitinib, on other spirometry, PRO, and QoL, 3. To evaluate the PK of frevecitinib INCLUSION CRITERIA: 1. Is capable of understanding the written informed consent, provides signed and witnessed written informed consent prior to any study‐related procedures, and agrees to comply with protocol requirements. 2. Able to understand and comply with the protocol requirements of the study, as judged by the investigator or designee. 3. Is 18 to 75 years of age (both inclusive) at the time of signing informed consent., 4. Body mass inde Xbetween [CCI] and weight [CCI] at screening. 5. Documented physician‐diagnosed asthma for at least 12 months prior to screening. 6. Has received a physician‐prescribed asthma controller regimen with medium dose or high dose ICS plus LABA, with or without additional controller medications, for at least 6 months prior to screening and the dose of ICS and additional controller(s) must be stable for at least 4 weeks prior to screening and throughout the screening/run‐in period. • High dose ICS equates to a total daily dose of >500 µg fluticasone p SECONDARY OUTCOME: Secondary end point(s):1. Incidence of AEs (including SAEs, TEAEs, and AESIs) collected throughout the study Secondary end point(s):10. Change in AM and PM asthma symptom scores from baseline to Week 121 Secondary end point(s):11. Change in AM and PM SABA rescue medication use (puffs) from baseline to Week 12 Secondary end point(s):12. Change in nighttime awakenings due to asthma from baseline to Week 12 Secondary end point(s):13. Symptom‐free 24‐hour periods (symptom‐free days) to Week 12 Secondary end point(s):14. Asthma control 24‐hour periods (asthma control days) to Week 12 Secondary end point(s):15. Rescue‐free 24‐hour periods (rescue‐free days) to Week 12 Secondary end point(s):16. Rate of severe asthma exacerbations and time to first severe asthma exacerbation Secondary end point(s):17. Rate of asthma worsening events and time to first asthma worsening event Secondary end point(s):18. Rate of exacerbations via CompE Xalgorithm and time to first CompE Xevent Secondary end point(s):19. Change from baseline to Week 12 and change from baseline to Week 2, Week 4, Week 8, and Week 12 in predose (pre‐bronchodilator) FeNO levels Secondary end point(s):2. Abnormal findings in clinical safety laboratory evaluations, ECGs, vital signs, and physical examinations throughout the study Secondary end point(s):20. Change from baseline to Week 12 in EQ‐5D‐5L Secondary end point(s):21. Change from baseline to Week 12 in WPAI+CIQ Secondary end point(s):22. PGI‐C, CGI‐C, and PGI‐S general assessments at Week 12/EOT Secondary end point(s):23. Serial PK parameters for frevecitinib and its metabolite [CCI], including but not limited to; Cmax, Tmax, AUC, and T1/2 following the first dose and at steady state Secondary end point(s):24. Population PK analysis Secondary end point(s):3. Change in predose (pre‐bronchodilator) FEV1 (% predicted) from baseline to Week 12 Secondary end point(s):4. Change in predose (pre‐bronchodilator) FEV1 (L) and FEV1 (% predicted) from baseline to Week 2, Week 4, and Week 8 Secondary end point(s):5. Change in morning and evening PEF from baseline to Week 12 Secondary end point(s):6. Change in ACQ‐6 score from baseline to Week 12 Secondary end point(s):7. Change in AQLQ score from baseline to Week 12 Secondary end point(s):8. Change from baseline to Week 12 in other lung function parameters (eg, FVC, FEF25‐75%, FEV1/FVC % predicted) Secondary end point(s):9. Change from baseline to Week 2, Week 4, Week 8, and Week 12 in other lung function parameters (eg, FVC, FEF 25‐75%, FEV1/FVC % predicted)