Influenza Antiviral DAS181-F03

Influenza Clinical Trial

Official title: A Phase I C Clinical Study With Influenza Antiviral DAS181-F03: Double-Blind, Randomized, Placebo-Controlled, Single Dose and Multiple Dose Escalation Study in Healthy Adults

Status Completed

Clinical Trial Summary

Influenza (flu) is a common respiratory infection and often causes severe illness. Few drugs are currently approved to treat influenza. This research will test the safety of an experimental anti-influenza drug called DAS181 that is given through an inhaler. The purpose of this study is to evaluate the safety of this new medication and how the body reacts to it. Any side effects will be measured by symptoms, physical examination or laboratory studies. About 27 healthy men and women age 18-45, who meet screening requirements, will participate. Three separate groups will be enrolled, with approximately 9 subjects in each group. Cohort 1:20 mg DAS181 or placebo for 1 day (total dose of 20 mg). Cohort 2: 20 mg DAS181 or placebo for 10 consecutive days (total dose of 200 mg). Cohort 3: 30 mg DAS 181 or placebo for 1 day (total dose of 30 mg.) Procedures include blood samples, electrocardiograms (measures heart activity) and breathing tests.

Clinical Trial Description

Influenza is typically caused by infection of two types of viruses, influenza virus A and influenza virus B. The host cell receptors for influenza A and B viruses are cell surface sialic acids (SA). The Actinomyces viscosus sialidase Catalytic Domain (AvCD) sialidase domain in DAS181 selectively cleaves sialic acids from the host cells, thereby rendering them inaccessible to the influenza viral particles that require sialic acids as receptors. By binding to the negatively charged glycosaminoglycans on the surface of airway epithelial cells, the cationic C-terminal Amphiregulin (AR) tag anchors DAS181 on the respiratory epithelium, thereby improving treatment potency and retention of the investigational drug on the airway surface. DAS181 is the first candidate in a new class of influenza therapeutics, viral receptor inactivator. The primary objective is to determine the safety and tolerability of DAS181 encapsulated dry powder compared to placebo when administered by oral inhalation using a dry powder inhaler (DPI) in healthy adults. The secondary objective of this study is to investigate the pharmacokinetic and immunologic profile of DAS181 encapsulated dry powder dose to dose and compared to placebo when administered by oral inhalation using a DPI in healthy adults. A total of 27 normal healthy male and female subjects (9 per cohort) 18 to 45 years of age at the time of screening will be included in this study. This study will be a double-blind, randomized, placebo-controlled study of a three cohorts. Cohort 1:20 mg DAS181 or placebo for 1 day (total dose of 20 mg). Cohort 2: 20 mg DAS181 or placebo for 10 consecutive days (total dose of 200 mg). Cohort 3: 30 mg DAS 181 or placebo for 1 day (total dose of 30 mg.) The study will proceed to the next stage of multiple daily doses based on meeting study defined criteria. Within each dose cohort of nine, subjects will be randomly assigned to DAS181 or placebo at 2:1 ratios. Subjects will be admitted to the inpatient clinic on the day prior to first dose (Day -1). The subjects in single dose cohorts (Cohort 1 and 3) will stay in the inpatient unit for dosing (Day 0) and one day after dosing (Day 1). Subjects in Cohort 1 will come back for follow-up visits on Study Days 2, 3, 7, 14, and 30 . Subjects in Cohort 3 will return on Days 2, 3, 4, 5, 8. 10, 16, and 30. The subjects in the 10-day, multiple-dose cohort (Cohort 2) will stay in the inpatient clinic from Day -1 to 1 and will be required to come back for follow-up visits on Days 2 - 7. They will be seen (and optionally readmitted) Days 8 - 10 and will be seen as outpatients Days 11, 13, 15, 17, 20, 22, 24, and 27. All subjects will be asked to return for an additional blood draw to conduct an immunogenicity test at 90 days post final dosing. Subjects will be trained in proper inhalation techniques prior to dosing using a low range inspiratory flow measurement device. ;

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Influenza
• Influenza, Human

• NCT number: NCT01173224
• Study type: Interventional
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Status: Completed
• Phase: Phase 1
• Start date: November 2010
• Completion date: September 2011