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<bold>Background:</bold> Multiple pro-inflammatory mediators implicated in the pathogenesis of moderate to severe asthma signal via the JAK/STAT pathway. KN-002 is a potent pan-JAK inhibitor formulated as a dry powder for oral inhalation. <bold>Methods:</bold> This Phase 1b, randomized, double-blinded, placebo-controlled study (<ext-link>NCT05006521</ext-link>) evaluated the safety and pharmacokinetics (PK) of KN-002 after 10-day administration of 4 mg BID to subjects with moderate to severe asthma using ICS/LABA therapy. Adverse Events (AEs) were recorded at each visit with hematology/chemistry samples collected at screening, Days 1-3, 6, 9-12 and 17. Intensive PK sampling was assessed on Days 1 and 10 (predose, 0.5, 1, 2, 3, 4, 6, 8, and 12 hrs [Day 1] plus 24 and 48 hrs post dose [Day 10]) and predose on Days 2 to 9. <bold>Results:</bold> 23 subjects (17 KN-002:6 placebo) received treatment. No serious/severe AEs were reported and no subjects withdrew. 10 (58.8%) KN-002 and 2 (33.3%) placebo reported AEs. The most common AE was headache; 3 [17.6%] KN-002 and 1 [16.7%] placebo. Two AEs, mild sore throat and moderate headache, were reported as possibly related to KN 002; both resolved without dosing change. Clinical laboratory outcomes revealed no findings of clinical concern. Steady state PK was achieved by Day 3 with minimal accumulation upon repeat dosing. Plasma levels were below pharmacologically active concentrations. The KN-002 safety/PK profile was consistent with that reported in subjects with ICS naïve mild asthma. <bold>Conclusions:</bold> Inhaled KN-002 was well tolerated by subjects with moderate to severe asthma using ICS/LABA. Outcomes support the Phase 2 development in subjects with uncontrolled asthma using medium to high dose ICS/LABA treatment.