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

• Sponsor: MedImmune LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02603952
• Collaborator: (none)
• Enrollment: 126
• Locations: 31
• Arms: 4
• Actual Duration (Months): 12.1
• Patients Per Site: 4.1
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Influenza	Drug: Oseltamivir; Drug: MEDI8852; Drug: Placebo	Phase 1/Phase 2

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 126 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Dec 7, 2015
• Actual Primary Completion Date: Dec 9, 2016
• Actual Study Completion Date: Dec 9, 2016

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo + Oseltamivir 75 mg 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; 75 mg capsules orally BID from Day 1 to Day 5.; Drug: Placebo; Placebo is salt-water solution containing no active ingredients and administered as a single IV infusion on Day 1.
Experimental: MEDI8852 750 mg + Oseltamivir 75 mg 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; 75 mg capsules orally BID from Day 1 to Day 5.; Drug: MEDI8852; MEDI8852 is a human IgG1 kappa monoclonal antibody (mAb) administered as a single IV infusion of 750 mg or 3000 mg on Day 1.
Experimental: MEDI8852 3000 mg + Oseltamivir 75 mg 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; 75 mg capsules orally BID from Day 1 to Day 5.; Drug: MEDI8852; MEDI8852 is a human IgG1 kappa monoclonal antibody (mAb) administered as a single IV infusion of 750 mg or 3000 mg on Day 1.
Experimental: MEDI8852 3000 mg Participants will receive a single IV infusion of MEDI8852 3000 mg on Day 1.	Drug: MEDI8852; MEDI8852 is a human IgG1 kappa monoclonal antibody (mAb) administered as a single IV infusion of 750 mg or 3000 mg on Day 1.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Any Solicited Influenza Symptoms From Day 1 Through Day 10 [Day 1 (post-dose) through Day 10]

   Solicited influenza symptoms included cough, nasal congestion, sore throat, aches and pains, fatigue (tiredness), headache, chills/sweats (feeling feverish).

2. Number of Participants With Any Solicited Influenza Symptoms From Day 10 Through Day 13 [Day 10 through Day 13]

   Solicited influenza symptoms included cough, nasal congestion, sore throat, aches and pains, fatigue (tiredness), headache, chills/sweats (feeling feverish).

3. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Day 1 (post-dose) through Day 28]

   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.

4. Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs) [Day 1 (post-dose) through Day 101]

   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.

5. Number of Participants With Treatment Emergent Adverse Events of Special Interest (TEAESIs) [Day 1 (post-dose) through Day 101]

   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.

Secondary Outcome Measures

1. Percentage of Participants With Influenza Viral Shedding as Measured by Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) [Baseline (Day 1) and Days 3, 5, 7, 9, 11, and 13]

   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.

2. Quantitation of Influenza Viral Shedding as Measured by qRT-PCR [Baseline (Day 1) and Days 3, 5, 7, 9, 11, and 13]

   qRT-PCR was used to measure influenza viral shedding from the nasopharyngeal swabs.

3. Number of Days of Influenza Viral Shedding as Measured by qRT-PCR [From Baseline (Day 1) to Day 7; and Day 9 to Day 13]

   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.

4. Percentage of Participants With Amino Acid Changes in MEDI8852 Binding Site [From Baseline (Day 1) to Day 13]

   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.

5. Number of Participants With Viral Susceptibility to MEDI8852 as Determined by a Cell Based Microneutralization Assay [From Baseline (Day 1) to Day 13]

   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.

6. Percentage of Participants With Virus Containing Known Oseltamivir Resistance-Associated Mutations [From Baseline (Day 1) to Day 13]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Canoga Park	California	United States	91303
2	Research Site	Long Beach	California	United States	90806
3	Research Site	Los Angeles	California	United States	90017
4	Research Site	Upland	California	United States	91786
5	Research Site	Hialeah	Florida	United States	33012
6	Research Site	Hialeah	Florida	United States	33013
7	Research Site	Hialeah	Florida	United States	33016
8	Research Site	Miami Lakes	Florida	United States	33014
9	Research Site	Miami	Florida	United States	33165
10	Research Site	Miami	Florida	United States	33173
11	Research Site	Miami	Florida	United States	33185
12	Research Site	North Miami Beach	Florida	United States	33162
13	Research Site	Avon	Indiana	United States	46123
14	Research Site	Muncie	Indiana	United States	47304
15	Research Site	New Orleans	Louisiana	United States	70124
16	Research Site	Troy	Michigan	United States	48085
17	Research Site	Butte	Montana	United States	59701
18	Research Site	Hickory	North Carolina	United States	28602
19	Research Site	Shelby	North Carolina	United States	28150
20	Research Site	Smithfield	Pennsylvania	United States	15478
21	Research Site	San Antonio	Texas	United States	78229
22	Research Site	Clinton	Utah	United States	84015
23	Research Site	Brandfort		South Africa	9400
24	Research Site	Durban		South Africa	4001
25	Research Site	Johannesburg		South Africa	2113
26	Research Site	Pretoria		South Africa	0087
27	Research Site	Pretoria		South Africa	0157
28	Research Site	Pretoria		South Africa	0181
29	Research Site	Pretoria		South Africa	0183
30	Research Site	Thabazimbi		South Africa	0380
31	Research Site	Welkom		South Africa	9460

Sponsors and Collaborators

• MedImmune LLC

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: MedImmune LLC
• ClinicalTrials.gov Identifier: NCT02603952
• Other Study ID Numbers: D6000C00002
• First Posted: Nov 13, 2015
• Last Update Posted: Jun 8, 2018
• Last Verified: May 1, 2018

• Keywords provided by MedImmune LLC: Influenza; Influenza A; Flu; Flu A
• Additional relevant MeSH terms: Influenza, Human; Oseltamivir; MEDI8852

Study Results

Participant Flow

Recruitment Details	The study was conducted from 07 Dec 2015 to 09 Dec 2016 in Australia, South Africa and United States of America.
Pre-assignment Detail	A total of 373 participants were screened, of which 247 participants were screen failures and 126 participants were randomized in the study.

Arm/Group Title	Placebo + Oseltamivir 75 mg	MEDI8852 750 mg + Oseltamivir 75 mg	MEDI8852 3000 mg + Oseltamivir 75 mg	MEDI8852 3000 mg
Arm/Group Description	Participants received 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.	Participants received a single IV infusion of MEDI8852 750 mg on Day 1 and oseltamivir 75 mg capsules orally BID from Day 1 to Day 5.	Participants received a single IV infusion of MEDI8852 3000 mg on Day 1 and oseltamivir 75 mg capsules orally BID from Day 1 to Day 5.	Participants received a single IV infusion of MEDI8852 3000 mg on Day 1.
Period Title: Overall Study
STARTED	32	31	31	32
Treated	32	31	31	31
COMPLETED	31	31	31	31
NOT COMPLETED	1	0	0	1

Baseline Characteristics

Arm/Group Title	Placebo + Oseltamivir 75 mg	MEDI8852 750 mg + Oseltamivir 75 mg	MEDI8852 3000 mg + Oseltamivir 75 mg	MEDI8852 3000 mg	Total
Arm/Group Description	Participants received 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.	Participants received a single IV infusion of MEDI8852 750 mg on Day 1 and oseltamivir 75 mg capsules orally BID from Day 1 to Day 5.	Participants received a single IV infusion of MEDI8852 3000 mg on Day 1 and oseltamivir 75 mg capsules orally BID from Day 1 to Day 5.	Participants received a single IV infusion of MEDI8852 3000 mg on Day 1.	Total of all reporting groups
Overall Participants	32	31	31	32	126
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	42.3 (11.97)	40.5 (11.97)	41.7 (12.90)	44.3 (13.96)	42.2 (12.66)
Sex: Female, Male (Count of Participants)
Female	20 62.5%	13 41.9%	18 58.1%	15 46.9%	66 52.4%
Male	12 37.5%	18 58.1%	13 41.9%	17 53.1%	60 47.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	16 50%	17 54.8%	20 64.5%	17 53.1%	70 55.6%
Not Hispanic or Latino	16 50%	14 45.2%	11 35.5%	15 46.9%	56 44.4%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	1 3.1%	0 0%	0 0%	0 0%	1 0.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	5 15.6%	8 25.8%	3 9.7%	5 15.6%	21 16.7%
White	26 81.3%	23 74.2%	28 90.3%	27 84.4%	104 82.5%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Any Solicited Influenza Symptoms From Day 1 Through Day 10
Description	Solicited influenza symptoms included cough, nasal congestion, sore throat, aches and pains, fatigue (tiredness), headache, chills/sweats (feeling feverish).
Time Frame	Day 1 (post-dose) through Day 10

Outcome Measure Data

Analysis Population Description

As-treated population included all participants who were randomized and received any portion of their protocol-specified treatment regimen.

Arm/Group Title	Placebo + Oseltamivir 75 mg	MEDI8852 750 mg + Oseltamivir 75 mg	MEDI8852 3000 mg + Oseltamivir 75 mg	MEDI8852 3000 mg
Arm/Group Description	Participants received 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.	Participants received a single IV infusion of MEDI8852 750 mg on Day 1 and oseltamivir 75 mg capsules orally BID from Day 1 to Day 5.	Participants received a single IV infusion of MEDI8852 3000 mg on Day 1 and oseltamivir 75 mg capsules orally BID from Day 1 to Day 5.	Participants received a single IV infusion of MEDI8852 3000 mg on Day 1.
Measure Participants	32	31	31	31
Any symptom	32 100%	31 100%	31 100%	31 96.9%

2. Primary Outcome

Title	Number of Participants With Any Solicited Influenza Symptoms From Day 10 Through Day 13
Description	Solicited influenza symptoms included cough, nasal congestion, sore throat, aches and pains, fatigue (tiredness), headache, chills/sweats (feeling feverish).
Time Frame	Day 10 through Day 13

Outcome Measure Data

Analysis Population Description

As-treated population included all participants who were randomized and received any portion of their protocol-specified treatment regimen.

Arm/Group Title	Placebo + Oseltamivir 75 mg	MEDI8852 750 mg + Oseltamivir 75 mg	MEDI8852 3000 mg + Oseltamivir 75 mg	MEDI8852 3000 mg
Arm/Group Description	Participants received 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.	Participants received a single IV infusion of MEDI8852 750 mg on Day 1 and oseltamivir 75 mg capsules orally BID from Day 1 to Day 5.	Participants received a single IV infusion of MEDI8852 3000 mg on Day 1 and oseltamivir 75 mg capsules orally BID from Day 1 to Day 5.	Participants received a single IV infusion of MEDI8852 3000 mg on Day 1.
Measure Participants	32	31	31	31
Any symptom	11 34.4%	14 45.2%	18 58.1%	11 34.4%

3. Primary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Description	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.
Time Frame	Day 1 (post-dose) through Day 28

Outcome Measure Data

Analysis Population Description

As-treated population included all participants who were randomized and received any portion of their protocol-specified treatment regimen.

Arm/Group Title	Placebo + Oseltamivir 75 mg	MEDI8852 750 mg + Oseltamivir 75 mg	MEDI8852 3000 mg + Oseltamivir 75 mg	MEDI8852 3000 mg
Arm/Group Description	Participants received 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.	Participants received a single IV infusion of MEDI8852 750 mg on Day 1 and oseltamivir 75 mg capsules orally BID from Day 1 to Day 5.	Participants received a single IV infusion of MEDI8852 3000 mg on Day 1 and oseltamivir 75 mg capsules orally BID from Day 1 to Day 5.	Participants received a single IV infusion of MEDI8852 3000 mg on Day 1.
Measure Participants	32	31	31	31
Count of Participants [Participants]	9 28.1%	11 35.5%	15 48.4%	12 37.5%

4. Primary Outcome

Title	Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs)
Description	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.
Time Frame	Day 1 (post-dose) through Day 101

Outcome Measure Data

Analysis Population Description

As-treated population included all participants who were randomized and received any portion of their protocol-specified treatment regimen.

Arm/Group Title	Placebo + Oseltamivir 75 mg	MEDI8852 750 mg + Oseltamivir 75 mg	MEDI8852 3000 mg + Oseltamivir 75 mg	MEDI8852 3000 mg
Arm/Group Description	Participants received 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.	Participants received a single IV infusion of MEDI8852 750 mg on Day 1 and oseltamivir 75 mg capsules orally BID from Day 1 to Day 5.	Participants received a single IV infusion of MEDI8852 3000 mg on Day 1 and oseltamivir 75 mg capsules orally BID from Day 1 to Day 5.	Participants received a single IV infusion of MEDI8852 3000 mg on Day 1.
Measure Participants	32	31	31	31
Count of Participants [Participants]	1 3.1%	0 0%	1 3.2%	0 0%

5. Primary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events of Special Interest (TEAESIs)
Description	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.
Time Frame	Day 1 (post-dose) through Day 101

Outcome Measure Data

Analysis Population Description

As-treated population included all participants who were randomized and received any portion of their protocol-specified treatment regimen.

Arm/Group Title	Placebo + Oseltamivir 75 mg	MEDI8852 750 mg + Oseltamivir 75 mg	MEDI8852 3000 mg + Oseltamivir 75 mg	MEDI8852 3000 mg
Arm/Group Description	Participants received 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.	Participants received a single IV infusion of MEDI8852 750 mg on Day 1 and oseltamivir 75 mg capsules orally BID from Day 1 to Day 5.	Participants received a single IV infusion of MEDI8852 3000 mg on Day 1 and oseltamivir 75 mg capsules orally BID from Day 1 to Day 5.	Participants received a single IV infusion of MEDI8852 3000 mg on Day 1.
Measure Participants	32	31	31	31
Count of Participants [Participants]	0 0%	0 0%	1 3.2%	0 0%

6. Secondary Outcome

Title	Percentage of Participants With Influenza Viral Shedding as Measured by Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR)
Description	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.
Time Frame	Baseline (Day 1) and Days 3, 5, 7, 9, 11, and 13

Outcome Measure Data

Analysis Population Description

Per-protocol (PP) population included all randomized participants who received any portion of their protocol-specified treatment regimen with valid assay results from nasopharyngeal specimens obtained at any post-dosing time point. Participants without confirmed influenza A at baseline were excluded from the PP population.

Arm/Group Title	Placebo + Oseltamivir 75 mg	MEDI8852 750 mg + Oseltamivir 75 mg	MEDI8852 3000 mg + Oseltamivir 75 mg	MEDI8852 3000 mg
Arm/Group Description	Participants received 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.	Participants received a single IV infusion of MEDI8852 750 mg on Day 1 and oseltamivir 75 mg capsules orally BID from Day 1 to Day 5.	Participants received a single IV infusion of MEDI8852 3000 mg on Day 1 and oseltamivir 75 mg capsules orally BID from Day 1 to Day 5.	Participants received a single IV infusion of MEDI8852 3000 mg on Day 1.
Measure Participants	30	27	23	24
Baseline (Day 1)	100 312.5%	100 322.6%	100 322.6%	100 312.5%
Day 3	90 281.3%	88.9 286.8%	91.3 294.5%	95.8 299.4%
Day 5	56.7 177.2%	85.2 274.8%	60.9 196.5%	54.2 169.4%
Day 7	33.3 104.1%	59.3 191.3%	30.4 98.1%	37.5 117.2%
Day 9	3.3 10.3%	7.4 23.9%	4.3 13.9%	0.0 0%
Day 11	0.0 0%	0.0 0%	0.0 0%	4.2 13.1%
Day 13	0.0 0%	0.0 0%	0.0 0%	0.0 0%

7. Secondary Outcome

Title	Quantitation of Influenza Viral Shedding as Measured by qRT-PCR
Description	qRT-PCR was used to measure influenza viral shedding from the nasopharyngeal swabs.
Time Frame	Baseline (Day 1) and Days 3, 5, 7, 9, 11, and 13

Outcome Measure Data

Analysis Population Description

PP population included all randomized participants who received any portion of their protocol-specified treatment regimen with valid assay results from nasopharyngeal specimens obtained at any post-dosing time point. Participants without confirmed influenza A at baseline were excluded from the PP population.

Arm/Group Title	Placebo + Oseltamivir 75 mg	MEDI8852 750 mg + Oseltamivir 75 mg	MEDI8852 3000 mg + Oseltamivir 75 mg	MEDI8852 3000 mg
Arm/Group Description	Participants received 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.	Participants received a single IV infusion of MEDI8852 750 mg on Day 1 and oseltamivir 75 mg capsules orally BID from Day 1 to Day 5.	Participants received a single IV infusion of MEDI8852 3000 mg on Day 1 and oseltamivir 75 mg capsules orally BID from Day 1 to Day 5.	Participants received a single IV infusion of MEDI8852 3000 mg on Day 1.
Measure Participants	30	27	23	24
Baseline (Day 1)	6.37 (1.52)	6.62 (1.30)	6.92 (1.17)	6.34 (1.47)
Day 3	4.35 (1.36)	4.75 (1.31)	4.89 (1.39)	4.63 (1.33)
Day 5	3.45 (1.03)	3.31 (0.73)	3.43 (1.22)	3.73 (1.23)
Day 7	2.94 (0.47)	3.13 (0.93)	2.97 (0.71)	3.03 (0.57)
Day 9	3.12 (0.85)	3.76 (1.60)	2.80 (0.00)	2.80 (0.00)
Day 11	2.80 (0.00)	2.80 (0.00)	2.80 (0.00)	3.11 (0.63)
Day 13	2.80 (NA)

8. Secondary Outcome

Title	Number of Days of Influenza Viral Shedding as Measured by qRT-PCR
Description	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.
Time Frame	From Baseline (Day 1) to Day 7; and Day 9 to Day 13

Outcome Measure Data

Analysis Population Description

PP population. Participants without confirmed influenza A at baseline were excluded from the PP population. Participants with shedding data available for Day 1 to Day 7 and Day 9 to Day 13 were analyzed for this outcome measure.

Arm/Group Title	Placebo + Oseltamivir 75 mg	MEDI8852 750 mg + Oseltamivir 75 mg	MEDI8852 3000 mg + Oseltamivir 75 mg	MEDI8852 3000 mg
Arm/Group Description	Participants received 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.	Participants received a single IV infusion of MEDI8852 750 mg on Day 1 and oseltamivir 75 mg capsules orally BID from Day 1 to Day 5.	Participants received a single IV infusion of MEDI8852 3000 mg on Day 1 and oseltamivir 75 mg capsules orally BID from Day 1 to Day 5.	Participants received a single IV infusion of MEDI8852 3000 mg on Day 1.
Measure Participants	30	27	23	24
Day 1 to Day 7	4.7 (2.05)	5.8 (1.84)	4.9 (1.95)	4.8 (2.18)
Day 9 to Day 13	5.4 (2.94)	6.3 (2.60)	6.0 (2.45)	5.5 (2.78)

9. Secondary Outcome

Title	Percentage of Participants With Amino Acid Changes in MEDI8852 Binding Site
Description	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.
Time Frame	From Baseline (Day 1) to Day 13

Outcome Measure Data

Analysis Population Description

PP population. Participants without confirmed influenza A at baseline were excluded from the PP population. Participants with confirmed Influenza A positive and Influenza A concentrations greater than the lower limit of quantification (LLOQ) were analyzed.

Arm/Group Title	All MEDI8852 Participants
Arm/Group Description	Participants who received a single IV infusion of MEDI8852 750 mg on Day 1 and oseltamivir 75 mg capsules orally BID from Day 1 to Day 5; or a single IV infusion of MEDI8852 3,000 mg on Day 1 and oseltamivir 75 mg capsules orally BID from Day 1 to Day 5; or a single IV infusion of MEDI8852 3000 mg on Day 1.
Measure Participants	94
Number [Percentage of Participants]	0 0%

10. Secondary Outcome

Title	Number of Participants With Viral Susceptibility to MEDI8852 as Determined by a Cell Based Microneutralization Assay
Description	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.
Time Frame	From Baseline (Day 1) to Day 13

Outcome Measure Data

Analysis Population Description

PP population. Participants without confirmed influenza A at baseline were excluded from the PP population. Participants with quantifiable Influenza A (greater than LLOQ) and a unique hemagglutinin gene sequence were analyzed.

Arm/Group Title	All MEDI8852 Participants
Arm/Group Description	Participants who received a single IV infusion of MEDI8852 750 mg on Day 1 and oseltamivir 75 mg capsules orally BID from Day 1 to Day 5; or a single IV infusion of MEDI8852 3000 mg on Day 1 and oseltamivir 75 mg capsules orally BID from Day 1 to Day 5; or a single IV infusion of MEDI8852 3000 mg on Day 1.
Measure Participants	35
Count of Participants [Participants]	0 0%

11. Secondary Outcome

Title	Percentage of Participants With Virus Containing Known Oseltamivir Resistance-Associated Mutations
Description	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.
Time Frame	From Baseline (Day 1) to Day 13

Outcome Measure Data

Analysis Population Description

PP population. Participants without confirmed influenza A at baseline were excluded from the PP population. Participants with confirmed Influenza A positive and Influenza A concentrations greater than the LLOQ were analyzed.

Arm/Group Title	All Oseltamivir Participants
Arm/Group Description	Participants who received a single IV infusion of placebo (matched to MEDI8852) on Day 1 and oseltamivir 75 mg capsules orally BID from Day 1 to Day 5; or a single IV infusion of MEDI8852 750 mg on Day 1 and oseltamivir 75 mg capsules orally BID from Day 1 to Day 5; or a single IV infusion of MEDI8852 3,000 mg on Day 1 and oseltamivir 75 mg capsules orally BID from Day 1 to Day 5.
Measure Participants	94
Number [Percentage of Participants]	0 0%

Adverse Events

Time Frame	Treatment-Emergent Adverse Events (TEAEs) : Day 1 (post-dose) through Day 28; Treatment-Emergent Serious Adverse Events (TESAEs) : Day 1 (post-dose) through Day 101
Adverse Event Reporting Description	Safety analyses were performed on the as-treated population. As-treated population included all participants who were randomized and received any portion of their protocol-specified treatment regimen.
Arm/Group Title	Placebo + Oseltamivir 75 mg		MEDI8852 750 mg + Oseltamivir 75 mg		MEDI8852 3000 mg + Oseltamivir 75 mg		MEDI8852 3000 mg
Arm/Group Description	Participants received 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.		Participants received a single IV infusion of MEDI8852 750 mg on Day 1 and oseltamivir 75 mg capsules orally BID from Day 1 to Day 5.		Participants received a single IV infusion of MEDI8852 3000 mg on Day 1 and oseltamivir 75 mg capsules orally BID from Day 1 to Day 5.		Participants received a single IV infusion of MEDI8852 3000 mg on Day 1.
All Cause Mortality
	Placebo + Oseltamivir 75 mg		MEDI8852 750 mg + Oseltamivir 75 mg		MEDI8852 3000 mg + Oseltamivir 75 mg		MEDI8852 3000 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/32 (0%)		0/31 (0%)		0/31 (0%)		0/31 (0%)
Serious Adverse Events
	Placebo + Oseltamivir 75 mg		MEDI8852 750 mg + Oseltamivir 75 mg		MEDI8852 3000 mg + Oseltamivir 75 mg		MEDI8852 3000 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/32 (3.1%)		0/31 (0%)		1/31 (3.2%)		0/31 (0%)
Injury, poisoning and procedural complications
Infusion related reaction	0/32 (0%)	0	0/31 (0%)	0	1/31 (3.2%)	1	0/31 (0%)	0
Nervous system disorders
Syncope	1/32 (3.1%)	1	0/31 (0%)	0	0/31 (0%)	0	0/31 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo + Oseltamivir 75 mg		MEDI8852 750 mg + Oseltamivir 75 mg		MEDI8852 3000 mg + Oseltamivir 75 mg		MEDI8852 3000 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/32 (28.1%)		11/31 (35.5%)		15/31 (48.4%)		12/31 (38.7%)
Blood and lymphatic system disorders
Polycythaemia	0/32 (0%)	0	0/31 (0%)	0	1/31 (3.2%)	1	0/31 (0%)	0
Cardiac disorders
Sinus tachycardia	0/32 (0%)	0	0/31 (0%)	0	0/31 (0%)	0	1/31 (3.2%)	1
Ear and labyrinth disorders
Middle ear effusion	1/32 (3.1%)	1	0/31 (0%)	0	0/31 (0%)	0	0/31 (0%)	0
Gastrointestinal disorders
Diarrhoea	0/32 (0%)	0	0/31 (0%)	0	2/31 (6.5%)	2	2/31 (6.5%)	2
Dry mouth	0/32 (0%)	0	1/31 (3.2%)	1	1/31 (3.2%)	1	0/31 (0%)	0
Nausea	2/32 (6.3%)	2	2/31 (6.5%)	2	1/31 (3.2%)	1	1/31 (3.2%)	1
Vomiting	1/32 (3.1%)	1	1/31 (3.2%)	1	1/31 (3.2%)	2	1/31 (3.2%)	1
Dyspepsia	0/32 (0%)	0	1/31 (3.2%)	1	0/31 (0%)	0	0/31 (0%)	0
Paraesthesia oral	1/32 (3.1%)	1	0/31 (0%)	0	0/31 (0%)	0	0/31 (0%)	0
Constipation	1/32 (3.1%)	1	0/31 (0%)	0	0/31 (0%)	0	0/31 (0%)	0
General disorders
Administration site thrombosis	0/32 (0%)	0	0/31 (0%)	0	0/31 (0%)	0	1/31 (3.2%)	1
Infections and infestations
Bronchitis	1/32 (3.1%)	1	4/31 (12.9%)	4	5/31 (16.1%)	5	2/31 (6.5%)	2
Pharyngitis	1/32 (3.1%)	1	2/31 (6.5%)	2	0/31 (0%)	0	1/31 (3.2%)	1
Rhinitis	0/32 (0%)	0	0/31 (0%)	0	1/31 (3.2%)	1	1/31 (3.2%)	1
Sinusitis	0/32 (0%)	0	1/31 (3.2%)	1	1/31 (3.2%)	1	0/31 (0%)	0
Upper respiratory tract infection	0/32 (0%)	0	1/31 (3.2%)	1	3/31 (9.7%)	3	0/31 (0%)	0
Conjunctivitis	0/32 (0%)	0	1/31 (3.2%)	1	0/31 (0%)	0	0/31 (0%)	0
Ear infection	1/32 (3.1%)	1	0/31 (0%)	0	0/31 (0%)	0	0/31 (0%)	0
Furuncle	0/32 (0%)	0	0/31 (0%)	0	0/31 (0%)	0	1/31 (3.2%)	1
Tonsillitis	0/32 (0%)	0	1/31 (3.2%)	1	0/31 (0%)	0	0/31 (0%)	0
Investigations
Blood creatine phosphokinase increased	0/32 (0%)	0	0/31 (0%)	0	1/31 (3.2%)	1	0/31 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	0/32 (0%)	0	1/31 (3.2%)	1	0/31 (0%)	0	0/31 (0%)	0
Nervous system disorders
Dizziness	1/32 (3.1%)	1	0/31 (0%)	0	0/31 (0%)	0	1/31 (3.2%)	1
Dysgeusia	1/32 (3.1%)	1	1/31 (3.2%)	1	2/31 (6.5%)	2	0/31 (0%)	0
Paraesthesia	2/32 (6.3%)	2	0/31 (0%)	0	0/31 (0%)	0	0/31 (0%)	0
Psychiatric disorders
Insomnia	1/32 (3.1%)	1	0/31 (0%)	0	0/31 (0%)	0	0/31 (0%)	0
Respiratory, thoracic and mediastinal disorders
Bronchial hyperreactivity	0/32 (0%)	0	2/31 (6.5%)	2	0/31 (0%)	0	0/31 (0%)	0
Epistaxis	0/32 (0%)	0	1/31 (3.2%)	1	1/31 (3.2%)	1	0/31 (0%)	0
Cough	0/32 (0%)	0	0/31 (0%)	0	1/31 (3.2%)	1	0/31 (0%)	0
Paranasal sinus discomfort	1/32 (3.1%)	1	0/31 (0%)	0	0/31 (0%)	0	0/31 (0%)	0
Skin and subcutaneous tissue disorders
Dermatitis	0/32 (0%)	0	0/31 (0%)	0	1/31 (3.2%)	1	0/31 (0%)	0
Hyperhidrosis	0/32 (0%)	0	0/31 (0%)	0	0/31 (0%)	0	1/31 (3.2%)	1

Limitations/Caveats

[Not Specified]

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