A Phase 2a to Evaluate the Safety of MEDI8852 in Adults With Uncomplicated Influenza

Study Overview
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Brief Summary
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The purpose of this study is to evaluate safety and tolerability of a single dose of MEDI8852 when given with oseltamivir, the safety and tolerability of oseltamivir alone, and the safety and tolerability of a single dose of MEDI8852 alone in adult participants with acute, uncomplicated influenza caused by Type A strains.

Detailed Description
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The MEDI8852 phase 2a study will evaluate the safety and tolerability of a single intravenous (IV) dose of MEDI8852 administered in conjunction with oseltamivir, the safety and tolerability of oseltamivir alone and the safety and tolerability of a single IV dose of MEDI8852 alone in adult participants with confirmed acute, uncomplicated influenza caused by Type A strains. Enrollment is planned in the United States, South Africa, and Australia.

Official Title
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A Phase 2a, Randomized, Partial Double-blind, Single Dose, Active-controlled, Dose Ranging Study to Evaluate the Safety of MEDI8852 in Adults With Acute, Uncomplicated Influenza

Conditions
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Influenza

Intervention / Treatment
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* Drug: Oseltamivir
* Drug: MEDI8852
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 through 65 years at the time of screening. Symptomatic presumptive Influenza A infection with onset of symptoms less than or equal to (≤) 5 days prior to MEDI8852 administration and defined as the presence of: Fever of greater than or equal to (≥) 38.0 degrees Celsius (100.4 degrees Fahrenheit) at screening AND ≥ 1 moderate systemic symptom (headache, malaise, myalgia, sweats and/or chills, or fatigue) AND ≥ 1 moderate respiratory symptom (cough, sore throat, or nasal symptoms) Influenza A infection confirmed with positive rapid antigen test Able to complete the follow-up period through Day 101 as required by protocol (including telephone follow-up for Days 11 to 101) Females of childbearing potential who are sexually active with a nonsterilized male partner must use a highly effective method of contraception for at least 2 days prior to the first dose of investigational product and must agree to continue using such precautions through Day 101 of the study Exclusion Criteria: Hospitalized subjects. Receipt of influenza antiviral therapy within the preceding 14 days. Receipt of immunoglobulin or blood products within 6 months prior to screening. Known immunodeficiency due to illness, including human immunodeficiency virus (HIV), or due to drugs, including any course of glucocorticoid therapy exceeding 2 weeks of prednisone or equivalent at a dose of 20 mg daily or every other day within 6 months prior to screening. Current clinical evidence of pneumonia. Active bacterial infection requiring treatment with oral or parenteral antibiotics. History of malignancy other than treated non-melanoma skin cancers or locally-treated cervical cancer in previous 3 years. Any planned surgical procedure before completion of Day 101.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo + Oseltamivir 75 mg<br>Participants will receive a single intravenous (IV) infusion of placebo (matched to MEDI8852) on Day 1 and oseltamivir 75 milligrams (mg) capsules orally twice a day (BID) from Day 1 to Day 5. | Drug: Oseltamivir<br>* 75 mg capsules orally BID from Day 1 to Day 5.<br>Drug: Placebo<br>* Placebo is salt-water solution containing no active ingredients and administered as a single IV infusion on Day 1.<br>|
| Experimental: MEDI8852 750 mg + Oseltamivir 75 mg<br>Participants will receive a single IV infusion of MEDI8852 750 mg on Day 1 and oseltamivir 75 mg capsules orally BID from Day 1 to Day 5. | Drug: Oseltamivir<br>* 75 mg capsules orally BID from Day 1 to Day 5.<br>Drug: MEDI8852<br>* MEDI8852 is a human IgG1 kappa monoclonal antibody (mAb) administered as a single IV infusion of 750 mg or 3000 mg on Day 1.<br>|
| Experimental: MEDI8852 3000 mg + Oseltamivir 75 mg<br>Participants will receive a single IV infusion of MEDI8852 3000 mg on Day 1 and oseltamivir 75 mg capsules orally BID from Day 1 to Day 5. | Drug: Oseltamivir<br>* 75 mg capsules orally BID from Day 1 to Day 5.<br>Drug: MEDI8852<br>* MEDI8852 is a human IgG1 kappa monoclonal antibody (mAb) administered as a single IV infusion of 750 mg or 3000 mg on Day 1.<br>|
| Experimental: MEDI8852 3000 mg<br>Participants will receive a single IV infusion of MEDI8852 3000 mg on Day 1. | Drug: MEDI8852<br>* MEDI8852 is a human IgG1 kappa monoclonal antibody (mAb) administered as a single IV infusion of 750 mg or 3000 mg on Day 1.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Any Solicited Influenza Symptoms From Day 1 Through Day 10 | Solicited influenza symptoms included cough, nasal congestion, sore throat, aches and pains, fatigue (tiredness), headache, chills/sweats (feeling feverish). | Day 1 (post-dose) through Day 10 | 
| Number of Participants With Any Solicited Influenza Symptoms From Day 10 Through Day 13 | Solicited influenza symptoms included cough, nasal congestion, sore throat, aches and pains, fatigue (tiredness), headache, chills/sweats (feeling feverish). | Day 10 through Day 13 | 
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | An adverse event (AE) is any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent events were between administration of study drug and Day 28 that were absent before treatment or that worsened relative to pre-treatment state. | Day 1 (post-dose) through Day 28 | 
| Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) | A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent events were between administration of study drug and Day 101 that were absent before treatment or that worsened relative to pre-treatment state. | Day 1 (post-dose) through Day 101 | 
| Number of Participants With Treatment Emergent Adverse Events of Special Interest (TEAESIs) | An AE is any untoward medical occurrence attributed to study drug in a participant who received study drug. An AESI was one of scientific and medical interest specific to understanding of the study drug and may have required close monitoring and rapid communication by the investigator to the sponsor. Treatment-emergent events were between administration of study drug and Day 101 that were absent before treatment or that worsened relative to pre treatment state. | Day 1 (post-dose) through Day 101 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Influenza Viral Shedding as Measured by Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) | Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure influenza viral shedding from the nasopharyngeal swabs. Percentage of participants who shed influenza virus are reported. | Baseline (Day 1) and Days 3, 5, 7, 9, 11, and 13 | 
| Quantitation of Influenza Viral Shedding as Measured by qRT-PCR | qRT-PCR was used to measure influenza viral shedding from the nasopharyngeal swabs. | Baseline (Day 1) and Days 3, 5, 7, 9, 11, and 13 | 
| Number of Days of Influenza Viral Shedding as Measured by qRT-PCR | Number of days of viral shedding for participants who shed influenza virus is reported. qRT-PCR was used to measure influenza viral shedding from the nasopharyngeal swabs. | From Baseline (Day 1) to Day 7; and Day 9 to Day 13 | 
| Percentage of Participants With Amino Acid Changes in MEDI8852 Binding Site | Genotypic analysis was performed to identify all amino acid changes in MEDI8852 binding site between each baseline (Day1) sample and the participant's corresponding last sample sequenced. Percentage of participants with changes in the amino acid corresponding to MEDI8852 binding site is reported. Due to the fact that the percentage of participants with amino acid changes in MEDI8852 binding site was zero across all participant samples analyzed, no additional per arm analyses were performed. | From Baseline (Day 1) to Day 13 | 
| Number of Participants With Viral Susceptibility to MEDI8852 as Determined by a Cell Based Microneutralization Assay | Viral susceptibility to MEDI8852 was measured by a Madin-Darby canine kidney (MDCK) cell-based microneutralization assay (Virospot) for viruses recovered from baseline samples and viruses recovered from samples following treatment that contain amino acid changes within the MEDI8852 binding site. Participants with detectable levels (50% tissue culture infectious dose [TCID50]) of virus were considered susceptible and were reported. Due to the fact that the number of participants with viral susceptibility to MEDI8852 binding site was zero across all participant samples analyzed, no additional per arm analyses were performed. | From Baseline (Day 1) to Day 13 | 
| Percentage of Participants With Virus Containing Known Oseltamivir Resistance-Associated Mutations | Genotypic analysis was performed to identify all amino acid changes in neuraminidase (NA) gene between each baseline (Day1) sample and the participant's corresponding last sample sequenced. Percentage of participants with virus containing known oseltamivir resistance-associated mutations (change in the NA genes) is reported. Due to the fact that the percentage of participants with virus containing known oseltamivir resistance-associated mutation was zero across all participant samples analyzed, no additional per arm analyses were performed. | From Baseline (Day 1) to Day 13 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza, Influenza A, Flu, Flu A