SAD and MAD of Inhaled AR-501 in Health Adults and P. Aeruginosa Infected Cystic Fibrosis Subjects

Summary

Participation Requirements

Description

Three dose levels (low, medium and high) will be assessed in succession, first in healthy volunteer (HV) subjects, then in cystic fibrosis (CF) subjects. The study will be performed in 2 parts: Phase 1 part of the study in HV subjects will consist of a single-ascending-dose (SAD) cohort, followed by...

Three dose levels (low, medium and high) will be assessed in succession, first in healthy volunteer (HV) subjects, then in cystic fibrosis (CF) subjects. The study will be performed in 2 parts: Phase 1 part of the study in HV subjects will consist of a single-ascending-dose (SAD) cohort, followed by the HV multiple-ascending-dose (MAD) cohort. Phase 2a part of the study in CF subjects will consist of a MAD study design. The HV cohort will include up to 48 subjects. The CF cohort will have 42 subjects. Thus, the total number of subjects is 90. The Phase 1 HV study will be performed at a Phase 1 Clinical Study Unit and the Phase 2a will be performed at approximately 24 clinical trial sites located in the United States and possibly in Europe, some of which may be part of the Cystic Fibrosis Foundation (CFF)-accredited Therapeutic Development Network (TDN) or the European Cystic Fibrosis Society Clinical Trial Network (ECFS-CTN). Subjects who meet all eligibility criteria, including giving informed consent, will be enrolled and undergo a screening period of 28 days. The HV cohort will include up to 24 adult subjects in 3 dose groups (8 per dose group [Low, Medium and High]) for the SAD phase of the study. In each dose group, subjects will be randomly assigned in a 3:1 ratio to the active drug or placebo, resulting in 6 subjects receiving inhaled AR-501 and 2 receiving inhaled placebo in a double-blind manner. The HV MAD phase of the study will include 24 adult subjects in 3 dose groups (8 per dose group [Low, Medium and High]). In each dose group, subjects will be randomly assigned in a 3:1 ratio to active study drug or placebo, resulting in 6 subjects receiving inhaled AR-501 and 2 receiving inhaled placebo in a double-blind manner. All subjects in HV MAD cohorts will receive once weekly inhaled study drug (either AR-501 or matching placebo) for 4 weeks for a total of 5 doses. The CF MAD cohort will evaluate 3 different dose levels for a total of 42 adult CF. Of the 42 subjects, 30 will be randomized to receive one of the three ascending doses of AR-501, while 12 will be randomized to receive placebo. All subjects in CF cohorts will receive once weekly inhaled study drug (either AR-501 or matching placebo) for 2 weeks for a total of 3 doses. The primary purpose of this study is to assess preliminary clinical safety of inhaled AR-501. The true frequency of AEs is unknown, and the sample size cannot be estimated accurately. For unknown AEs, the probabilities of observing at least 1 AE among 36 total healthy adult subjects and 30 adult CF subjects receiving any AR-501 dose are ? 80% if the true rate of such events are at least 4.4% and 4.8% respectively.

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