A Study of MHAA4549A as Monotherapy for Acute Uncomplicated Seasonal Influenza A in Otherwise Healthy Adults

Study Overview
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Brief Summary
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This is a Phase 2, randomized, double-blind, placebo-controlled single dose study in otherwise healthy adults with acute uncomplicated seasonal influenza A to assess the safety and tolerability, efficacy, and pharmacokinetics of MHAA4549A.

Official Title
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A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial of MHAA4549A, a Monoclonal Antibody, Administered as Monotherapy for the Treatment of Acute Uncomplicated Seasonal Influenza A Infection in Otherwise Healthy Adults

Conditions
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Influenza A

Intervention / Treatment
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* Drug: MHAA4549A
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Otherwise healthy participants Positive test for influenza A infection No more than 72 hours elapsed between onset of influenza-like illness and start of study drug Presence of at least one moderate or severe constitutional symptom such as headache, myalgia, fever, chills, fatigue, anorexia, or nausea PLUS one moderate or severe respiratory symptom such as cough, sore throat, or rhinorrhea For women of childbearing potential: negative pregnancy test and agreement to use acceptable contraceptive methods for at least 120 days after study drug administration For men: agreement to use acceptable contraceptive methods for at least 30 days after study drug administration Exclusion Criteria: Creatinine clearance less than or equal to (</=) 80 milliliters per minute (mL/min) Any significant medical conditions or laboratory abnormalities Clinical signs and symptoms consistent with otitis, bronchitis, sinusitis, or pneumonia or active bacterial infection Use of antiviral therapy in the period from onset of influenza-like illness and prior to enrollment Pregnancy at Screening or is currently pregnant or breastfeeding Investigational therapy within 30 days or 5 half-lives prior to start of study drug, whichever is greater Prior anti-influenza monoclonal antibody use Receipt of a nasal influenza A vaccine within 14 days prior to Screening Positive test for influenza B or influenza A+B within 2 weeks prior to study drug History of significant tobacco use or drug/alcohol abuse Chronic use of oral or inhaled corticosteroids within 30 days prior to Screening Autoimmune disease, known immunodeficiency of any cause, or use of immunosuppressive medications History of any chronic respiratory condition Human immunodeficiency virus (HIV) with cluster of differentiation (CD) 4 count </= 200 cells per milliliter (cells/mL) in the past 12 months Serious infection requiring oral or IV antibiotics within 14 days prior to Screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MHAA4549A 3600 milligrams (mg)<br>Participants will receive single-dose MHAA4549A, 3600 mg, by intravenous (IV) administration. | Drug: MHAA4549A<br>* MHAA4549A will be administered as a single dose by IV administration.<br>|
| Experimental: MHAA4549A 8400 mg<br>Participants will receive single-dose MHAA4549A, 8400 mg, by IV administration. | Drug: MHAA4549A<br>* MHAA4549A will be administered as a single dose by IV administration.<br>|
| Placebo Comparator: Placebo<br>Participants will receive single-dose placebo by IV administration. | Drug: Placebo<br>* Placebo will be administered as a single dose by IV administration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Adverse Events (AEs) | An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not considered related to the study drug. | Baseline to Day 100 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Requiring Hospitalization for Influenza-Related Complications |  | Baseline to Day 100 | 
| Duration of Hospitalization for Influenza-Related Complications |  | Baseline to Day 100 | 
| Percentage of Participants Requiring Antibiotics for Secondary Bacterial Respiratory Infections | Participants with antibiotic usage for secondary bacterial respiratory infections were identified by counting participants with AEs containing the terms, pneumonia, lung, myocarditis, ARDS (acute respiratory distress syndrome), otitis media, or respiratory. | Baseline to Day 100 | 
| Percentage of Participants With Complications of Influenza | Participants with complications of influenza were identified by counting participants with AEs containing the terms, pneumonia, lung, myocarditis, ARDS (acute respiratory distress syndrome), otitis media, or respiratory. | Baseline to Day 100 | 
| Percentage of Participants With Influenza A Relapse/Reinfection |  | Baseline to Day 100 | 
| Area Under the Concentration-Time Curve (AUC) of MHAA4549A | The AUC is a measure of the plasma concentration of the drug over time. It is used to characterize drug absorption. AUC was measured in micrograms times hours per milliliter (mcg*h/mL). | Up to Day 100 (collections scheduled pre-dose [0 hours]; 60 minutes post-dose; and on Days 3, 5, 7, 30, and 100 post-dose; infusion duration = 2 hours) | 
| Maximum Serum Concentration (Cmax) of MHAA4549A |  | Up to Day 100 (collections scheduled pre-dose [0 hours]; 60 minutes post-dose; and on Days 3, 5, 7, 30, and 100 post-dose; infusion duration = 2 hours) | 
| Time to Alleviation of Symptoms of Influenza A Infection | Time to alleviation of all 7 symptoms (i.e., nasal congestion, sore throat, cough, aches, fatigue, headaches, chills/sweats) was assessed using a rating scale of 0 (none), 1 (mild), 2 (moderate), or 3 (severe) for each symptom. The outcome was defined in two ways: time to a total symptom score of <=1 and time to a total symptom score of <=7. Resolution had to be maintained for 24 hours without use of symptom relief medications. For participants who were enrolled with mild symptoms, the symptom score had to be reduced by one point during the study duration. | Baseline to Day 14 | 
| Percentage of Participants With Influenza-Related Deaths |  | Baseline to Day 100 |