A Study of MHAA4549A in Healthy Volunteers in an Influenza Challenge Model

Study Overview
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Brief Summary
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This randomized, double-blind, placebo-controlled study will evaluate the efficacy and safety of MHAA4549A in healthy volunteers in an influenza challenge model. Subjects will be intranasally oculated with the challenge virus and will be randomly assigned to receive a intravenous dose of either MHAA4549A or placebo. In the stage 5 cohort, subjects will be randomly assigned to receive doses of MHAA4549A or placebo or Tamiflu (oseltamivir) orally twice daily for 5 days. All subjects in all cohorts may take Tamiflu twice daily from Day 7 to Day 11.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Phase 2a Study in Healthy Volunteers to Evaluate the Efficacy and Safety of MHAA4549A in an Influenza Challenge Model

Conditions
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Healthy Volunteer

Intervention / Treatment
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* Drug: MHAA549A
* Drug: Placebo
* Drug: oseltamivir [Tamiflu]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: In good health with no history of major medical conditions from medical history, physical examination and routine laboratory tests Male subjects and women of child-bearing potential must use effective contraception as defined by protocol, starting at entry to quarantine and continuing until Day 120 follow-up visit Sero-suitable for challenge virus Exclusion Criteria: Women who have been pregnant within 6 months prior to the study, or who have been breastfeeding within 3 months prior to the study, or who have a positive pregnancy test at any point in the study Any history or evidence of any clinically significant cardiovascular, gastrointestinal, endocrinological, haematological, hepatic, immunological, metabolic, urological, neurological, psychiatric, renal, and/or other major disease or malignancy, as judged by the CI Abnormal pulmonary function evidenced by clinically significant abnormalities in spirometry History of asthma, COPD, pulmonary hypertension, reactive airway disease, or chronic lung disease of any etiology. A history of childhood asthma before the age of 12 is acceptable provided the subject is asymptomatic without treatment. History suggestive of respiratory infection within 14 days prior to admission to the unit

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MHAA4549A<br> | Drug: MHAA549A<br>* IV dose<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* IV dose<br>|
| Active Comparator: Tamiflu<br> | Drug: oseltamivir [Tamiflu]<br>* Orally b.i.d, 5 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Viral area under the concentration-time curve (AUC) of nasopharyngeal viral load by quantitative Polymerase Chain Reaction (qPCR) |  | 8 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Incidence of adverse events |  | 120 days | 
| Safety: Change in lung function |  | from pre-challenge to Day 29 | 
| Safety: Incidence of anti-therapeutic antibodies (ATAs) |  | 120 days | 
| Pharmacokinetics: Area under the concentration-time curve |  | 8 days | 
| AUC of nasopharyngeal viral load, as measured by cell culture |  | 8 days | 
| Peak viral load (qPCR and cell culture) |  | 8 days | 
| Duration of viral shedding |  | 8 days | 
| Duration of Grade 2 or worse symptoms (from first occurrence of any Grade >2 symptom to last occurrence of any Grade >2 symptom) |  | 8 days | 
| Peak/AUC of composite symptoms |  | 8 days |