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

• ClinicalTrials.gov Identifier: NCT02603952
• Recruitment Status: Completed
• First Posted: November 13, 2015
• Results First Posted: June 8, 2018
• Last Update Posted: June 8, 2018
• Sponsor: MedImmune LLC
• Information provided by (Responsible Party): MedImmune LLC

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Influenza
• Interventions: Drug: Oseltamivir; Drug: MEDI8852; Drug: Placebo
• Enrollment: 126

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 Details	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
Reason Not Completed
Withdrawal by Subject	1	0	0	0
Received oseltamivir by error	0	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 Number of Baseline Participants		32	31	31	32	126
Baseline Analysis Population Description		Intent-to-Treat population included all randomized participants.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	32 participants	31 participants	31 participants	32 participants	126 participants
		42.3 (11.97)	40.5 (11.97)	41.7 (12.90)	44.3 (13.96)	42.2 (12.66)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	32 participants	31 participants	31 participants	32 participants	126 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); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	32 participants	31 participants	31 participants	32 participants	126 participants
	Hispanic or Latino	16 50.0%	17 54.8%	20 64.5%	17 53.1%	70 55.6%
	Not Hispanic or Latino	16 50.0%	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 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	32 participants	31 participants	31 participants	32 participants	126 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	1 3.1%	0 0.0%	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 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 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	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.
Overall Number of Participants Analyzed	32	31	31	31
Measure Type: Count of Participants; Unit of Measure: Participants
Any symptom	32 100.0%	31 100.0%	31 100.0%	31 100.0%

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.
Overall Number of Participants Analyzed	32	31	31	31
Measure Type: Count of Participants; Unit of Measure: Participants
Any symptom	11 34.4%	14 45.2%	18 58.1%	11 35.5%

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.
Overall Number of Participants Analyzed	32	31	31	31
Measure Type: Count of Participants; Unit of Measure: Participants
	9 28.1%	11 35.5%	15 48.4%	12 38.7%

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.
Overall Number of Participants Analyzed	32	31	31	31
Measure Type: Count of Participants; Unit of Measure: Participants
	1 3.1%	0 0.0%	1 3.2%	0 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.
Overall Number of Participants Analyzed	32	31	31	31
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%	1 3.2%	0 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.
Overall Number of Participants Analyzed	30	27	23	24
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
Baseline (Day 1)	100; (88.4 to 100)	100; (87.2 to 100)	100; (85.2 to 100)	100; (85.8 to 100)
Day 3	90; (73.5 to 97.9)	88.9; (70.8 to 97.6)	91.3; (72.0 to 98.9)	95.8; (78.9 to 99.9)
Day 5	56.7; (37.4 to 74.5)	85.2; (66.3 to 95.8)	60.9; (38.5 to 80.3)	54.2; (32.8 to 74.4)
Day 7	33.3; (17.3 to 52.8)	59.3; (38.8 to 77.6)	30.4; (13.2 to 52.9)	37.5; (18.8 to 59.4)
Day 9	3.3; (0.1 to 17.2)	7.4; (0.9 to 24.3)	4.3; (0.1 to 21.9)	0.0; (0.0 to 14.2)
Day 11	0.0; (0.0 to 11.6)	0.0; (0.0 to 12.8)	0.0; (0.0 to 14.8)	4.2; (0.1 to 21.1)
Day 13	0.0; (0.0 to 11.6)	0.0; (0.0 to 12.8)	0.0; (0.0 to 14.8)	0.0; (0.0 to 14.2)

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.
Overall Number of Participants Analyzed		30	27	23	24
Mean (Standard Deviation); Unit of Measure: Log10 (viral copies/mL)
Baseline (Day 1)	Number Analyzed	30 participants	27 participants	23 participants	24 participants
		6.37 (1.52)	6.62 (1.30)	6.92 (1.17)	6.34 (1.47)
Day 3	Number Analyzed	29 participants	27 participants	22 participants	23 participants
		4.35 (1.36)	4.75 (1.31)	4.89 (1.39)	4.63 (1.33)
Day 5	Number Analyzed	28 participants	27 participants	21 participants	24 participants
		3.45 (1.03)	3.31 (0.73)	3.43 (1.22)	3.73 (1.23)
Day 7	Number Analyzed	30 participants	27 participants	22 participants	23 participants
		2.94 (0.47)	3.13 (0.93)	2.97 (0.71)	3.03 (0.57)
Day 9	Number Analyzed	7 participants	6 participants	3 participants	7 participants
		3.12 (0.85)	3.76 (1.60)	2.80 (0.00)	2.80 (0.00)
Day 11	Number Analyzed	3 participants	2 participants	3 participants	4 participants
		2.80 (0.00)	2.80 (0.00)	2.80 (0.00)	3.11 (0.63)
Day 13	Number Analyzed	0 participants	0 participants	0 participants	1 participants
					2.80 [1] (NA)

[1]

Standard deviation (SD) data not applicable as only one participant was evaluable for this time point.

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.
Overall Number of Participants Analyzed		30	27	23	24
Mean (Standard Deviation); Unit of Measure: Days
Day 1 to Day 7	Number Analyzed	23 participants	19 participants	17 participants	16 participants
		4.7 (2.05)	5.8 (1.84)	4.9 (1.95)	4.8 (2.18)
Day 9 to Day 13	Number Analyzed	7 participants	8 participants	6 participants	8 participants
		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.
Overall Number of Participants Analyzed	94
Measure Type: Number; Unit of Measure: Percentage of Participants
	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.
Overall Number of Participants Analyzed	35
Measure Type: Count of Participants; Unit of Measure: Participants
	0 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.
Overall Number of Participants Analyzed	94
Measure Type: Number; Unit of Measure: Percentage of Participants
	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 (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/32 (0.00%)		0/31 (0.00%)		0/31 (0.00%)		0/31 (0.00%)
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 (3.13%)		0/31 (0.00%)		1/31 (3.23%)		0/31 (0.00%)
Injury, poisoning and procedural complications
Infusion related reaction † 1	0/32 (0.00%)	0	0/31 (0.00%)	0	1/31 (3.23%)	1	0/31 (0.00%)	0
Nervous system disorders
Syncope † 1	1/32 (3.13%)	1	0/31 (0.00%)	0	0/31 (0.00%)	0	0/31 (0.00%)	0
1 Term from vocabulary, MedDRA 18.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	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 (28.13%)		11/31 (35.48%)		15/31 (48.39%)		12/31 (38.71%)
Blood and lymphatic system disorders
Polycythaemia † 1	0/32 (0.00%)	0	0/31 (0.00%)	0	1/31 (3.23%)	1	0/31 (0.00%)	0
Cardiac disorders
Sinus tachycardia † 1	0/32 (0.00%)	0	0/31 (0.00%)	0	0/31 (0.00%)	0	1/31 (3.23%)	1
Ear and labyrinth disorders
Middle ear effusion † 1	1/32 (3.13%)	1	0/31 (0.00%)	0	0/31 (0.00%)	0	0/31 (0.00%)	0
Gastrointestinal disorders
Diarrhoea † 1	0/32 (0.00%)	0	0/31 (0.00%)	0	2/31 (6.45%)	2	2/31 (6.45%)	2
Dry mouth † 1	0/32 (0.00%)	0	1/31 (3.23%)	1	1/31 (3.23%)	1	0/31 (0.00%)	0
Nausea † 1	2/32 (6.25%)	2	2/31 (6.45%)	2	1/31 (3.23%)	1	1/31 (3.23%)	1
Vomiting † 1	1/32 (3.13%)	1	1/31 (3.23%)	1	1/31 (3.23%)	2	1/31 (3.23%)	1
Dyspepsia † 1	0/32 (0.00%)	0	1/31 (3.23%)	1	0/31 (0.00%)	0	0/31 (0.00%)	0
Paraesthesia oral † 1	1/32 (3.13%)	1	0/31 (0.00%)	0	0/31 (0.00%)	0	0/31 (0.00%)	0
Constipation † 1	1/32 (3.13%)	1	0/31 (0.00%)	0	0/31 (0.00%)	0	0/31 (0.00%)	0
General disorders
Administration site thrombosis † 1	0/32 (0.00%)	0	0/31 (0.00%)	0	0/31 (0.00%)	0	1/31 (3.23%)	1
Infections and infestations
Bronchitis † 1	1/32 (3.13%)	1	4/31 (12.90%)	4	5/31 (16.13%)	5	2/31 (6.45%)	2
Pharyngitis † 1	1/32 (3.13%)	1	2/31 (6.45%)	2	0/31 (0.00%)	0	1/31 (3.23%)	1
Rhinitis † 1	0/32 (0.00%)	0	0/31 (0.00%)	0	1/31 (3.23%)	1	1/31 (3.23%)	1
Sinusitis † 1	0/32 (0.00%)	0	1/31 (3.23%)	1	1/31 (3.23%)	1	0/31 (0.00%)	0
Upper respiratory tract infection † 1	0/32 (0.00%)	0	1/31 (3.23%)	1	3/31 (9.68%)	3	0/31 (0.00%)	0
Conjunctivitis † 1	0/32 (0.00%)	0	1/31 (3.23%)	1	0/31 (0.00%)	0	0/31 (0.00%)	0
Ear infection † 1	1/32 (3.13%)	1	0/31 (0.00%)	0	0/31 (0.00%)	0	0/31 (0.00%)	0
Furuncle † 1	0/32 (0.00%)	0	0/31 (0.00%)	0	0/31 (0.00%)	0	1/31 (3.23%)	1
Tonsillitis † 1	0/32 (0.00%)	0	1/31 (3.23%)	1	0/31 (0.00%)	0	0/31 (0.00%)	0
Investigations
Blood creatine phosphokinase increased † 1	0/32 (0.00%)	0	0/31 (0.00%)	0	1/31 (3.23%)	1	0/31 (0.00%)	0
Metabolism and nutrition disorders
Decreased appetite † 1	0/32 (0.00%)	0	1/31 (3.23%)	1	0/31 (0.00%)	0	0/31 (0.00%)	0
Nervous system disorders
Dizziness † 1	1/32 (3.13%)	1	0/31 (0.00%)	0	0/31 (0.00%)	0	1/31 (3.23%)	1
Dysgeusia † 1	1/32 (3.13%)	1	1/31 (3.23%)	1	2/31 (6.45%)	2	0/31 (0.00%)	0
Paraesthesia † 1	2/32 (6.25%)	2	0/31 (0.00%)	0	0/31 (0.00%)	0	0/31 (0.00%)	0
Psychiatric disorders
Insomnia † 1	1/32 (3.13%)	1	0/31 (0.00%)	0	0/31 (0.00%)	0	0/31 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Bronchial hyperreactivity † 1	0/32 (0.00%)	0	2/31 (6.45%)	2	0/31 (0.00%)	0	0/31 (0.00%)	0
Epistaxis † 1	0/32 (0.00%)	0	1/31 (3.23%)	1	1/31 (3.23%)	1	0/31 (0.00%)	0
Cough † 1	0/32 (0.00%)	0	0/31 (0.00%)	0	1/31 (3.23%)	1	0/31 (0.00%)	0
Paranasal sinus discomfort † 1	1/32 (3.13%)	1	0/31 (0.00%)	0	0/31 (0.00%)	0	0/31 (0.00%)	0
Skin and subcutaneous tissue disorders
Dermatitis † 1	0/32 (0.00%)	0	0/31 (0.00%)	0	1/31 (3.23%)	1	0/31 (0.00%)	0
Hyperhidrosis † 1	0/32 (0.00%)	0	0/31 (0.00%)	0	0/31 (0.00%)	0	1/31 (3.23%)	1
1 Term from vocabulary, MedDRA 18.1; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

MedImmune has 60 days to review results communications prior to public release and may delete information that compromises on-going studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.

Results Point of Contact

• Name/Title: Raburn Mallory
• Organization: MedImmune, LLC
• Phone: 301-398-4095
• EMail: information.center@astrazeneca.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ali SO, Takas T, Nyborg A, Shoemaker K, Kallewaard NL, Chiong R, Dubovsky F, Mallory RM. Evaluation of MEDI8852, an Anti-Influenza A Monoclonal Antibody, in Treating Acute Uncomplicated Influenza. Antimicrob Agents Chemother. 2018 Oct 24;62(11):e00694-18. doi: 10.1128/AAC.00694-18. Print 2018 Nov.

• Responsible Party: MedImmune LLC
• ClinicalTrials.gov Identifier: NCT02603952
• Other Study ID Numbers: D6000C00002
• First Submitted: November 2, 2015
• First Posted: November 13, 2015
• Results First Submitted: February 15, 2018
• Results First Posted: June 8, 2018
• Last Update Posted: June 8, 2018