A phase 1, double-blind placebo-controlled single and multiple ascending dose study of the safety, tolerability, pharmacokinetics, pharmacodynamics and food effects of IFM-2427 in healthy subjects

INTERVENTION: Part A: IFM‐2427 or placebo will be given once, as an oral drink. After administration of the study compound, the vial will be rinsed twice with water which the volunteer will also be required to drink. The volunteer may need to drink an additional amount of water. Administration of the study compound will be done after an overnight fast (no eating and drinking, except water) of at least 8 hours. A light meal will be given on the evening before fasting. During fasting the volunteer is allowed to drink water, except from 2 hour before until 1 hour after administration of the study compound. Following administration, the volunteer will fast for another 4 hours. Then the volunteer will be given a lunch. Whether the volunteer will receive IFM‐2427 or placebo will be determined by chance. Per group, 6 volunteers will receive IFM‐2427 and 2 volunteers will receive placebo. Neither the volunteer, nor the responsible doctor knows if IFM‐2427 or placebo will be administered; we call this a double‐blinded study. However, if it is important for the volunteers health, for example in case of a serious side effect, this information can be looked up during the study. For safety reasons, initially 2 volunteers in Group 1 will receive the study compound. One volunteer will receive IFM‐2427, and 1 will receive placebo. After administration, the safety and tolerability of the study compound in these 2 volunteers will be closely monitored. If there are no concerns about the safety and tolerability 24 hours after administration, then the remaining 6 volunteers (5 will receive IFM‐2427 and 1 will receive placebo) in Group 1 will receive the study compound. Please refer to the table CONDITION: ; Crohns disease ; Inflammatory diseases 10017969 PRIMARY OUTCOME: Safety : Adverse events (AEs), clinical laboratory, vital signs, 12‐lead ; electrocardiogram (ECG), 24 hour Holter monitoring and physical examination ; Pharmacokinetics : Plasma concentrations of IFM 2427, and plasma PK parameters ; estimated using noncompartmental analysis (NCA), as appropriate: Cmax, tmax, ; AUC0‐last, AUC0 inf, t1/2, CL/F, and Vz/F (single‐dose PK; Parts A, B, and D), ; Cmax, tmax, AUC0‐*, t1/2, CLss/F, Vzss/F, Rac,AUC, and Rac,Cmax (multiple‐dose ; PK; Part C) ; Metabolite profiling in plasma samples taken from subjects of Group 2 in Part C ; Urine IFM 2427 concentrations and urine PK parameters including, but not ; limited to: Ae0‐*, Fe0‐*, and CLr (Part C); INCLUSION CRITERIA: ‐ Gender : male or female; females must be of non‐childbearing potential ‐ Age : 18 to 64 years, inclusive, at screening. ‐ Body mass inde X(BMI) : 18.5 to 30.0 kg/m2 at screening. ‐ Weight : >=50 kg at screening. SECONDARY OUTCOME: Pharmacodynamics : PD parameters and exploratory biomarkers: ; ‐ Blood cell release of IL‐1β and IL‐18 following e Xvivo stimulation with an ; activator of the NLRP3 inflammasome compared to control conditions (Parts A and ; C) ; ‐ Exploratory PD (possible analyses of ribonucleic acid [RNA] transcriptomics ; and proteomics in the future) (Parts A and C) ; ‐ Potential induction of CYP3A due to IFM‐2427 based on calculating whether a ; change from baseline in the plasma 4β hydroxycholesterol/cholesterol ratio is ; observed (Part C) ; Pharmacogenomics : Sequencing of deoxyribonucleic acid (DNA) isolated from ; whole blood may be performed to: ; ‐ Determine carriers of clonal hematopoiesis of indeterminate potential based ; on a pre‐specified list of variants in up to 100 genetic loci ; ‐ Genotype the NLRP3 genetic locus ; ‐ Genotype loci related to NLRP3 signalling ; ‐ Analysis of whole‐exome or whole genome sequencing derived variants ;