126 A phase 1 clinical study of CTX-4430 in cystic fibrosis patients

Abstract

Objectives Safe, effective anti-inflammatory treatment (AIT) remains a significant unmet need for CF. Inflammation plays a central role in CF and is a key factor in lung function decline and exacerbations. CTX-4430 is an oral once daily AIT in development for CF. It acts by reducing production of Leukotriene B4, thereby modulating the excessive neutrophil burden characteristic of CF lung disease. Safety and inflammatory biomarkers were assessed over two weeks of treatment in phase 1 study in CF patients. Methods This ascending dose study was conducted at four clinical sites in the United Kingdom (NCT01944735). It included 17 patients with mild to moderate CF. Doses of 50 mg or 100 mg CTX-4430 or placebo were studied during 15 days of treatment. Safety measures were taken on days 1, 8 and 15, including assessments of adverse events, hematology, blood chemistries and pulmonary function. Experimental measures included serum CRP, sputum DNA, elastase and microbial counts. Additional assessments of pharmacokinetics and pharmacodynamics in blood are reported separately. Results Here we report the results of this phase 1 study in CF patients including assessments of safety and tolerability, pulmonary function and inflammatory markers in blood and sputum. In brief, CTX-4430 was safe and well tolerated at both dose levels. No deleterious changes in pulmonary function were observed. Treatment did not affect circulating neutrophil counts. Positive trends were observed in blood and sputum inflammatory markers demonstrating potential use of CTX-4430 to preserve CF lung function over time. Conclusion These results support further clinical development of CTX-4430 for treatment of CF.