Trial Outcomes & Findings for A Phase 1b/2a Randomized, Double-Blind, Placebo-controlled, Dose-escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MEDI8897, a Monoclonal Antibody With an Extended Half-life Against Respiratory Syncytial Virus, in Healthy Preterm Infants (NCT NCT02290340)

NCT ID: NCT02290340

Last Updated: 2018-09-19

Results Overview

An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. 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 situation (immediate risk of dying); persistent or significant disability/incapacity of a participant who received MEDI8897. TEAEs and TESAEs were the events that occurred between administration of study drug (Day 1) and Day 361 that were absent before treatment or that worsened relative to pre-treatment state.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 151 participants
• Primary outcome timeframe: From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)
• Results posted on: 2018-09-19

Participant Flow

Participants were recruited between January 2015 and September 2015 at 10 sites (USA, South Africa, and Chile) and followed for 1 year after dosing.

A total of 151 participants were screened in the study, of which 89 participants were randomized and treated.

Participant milestones

Measure	Placebo Participants received placebo intramuscularly.	MEDI8897 10 mg Participants received a single dose of MEDI8897 10 milligram (mg) intramuscularly.	MEDI8897 25 mg Participants received a single dose of MEDI8897 25 mg intramuscularly.	MEDI8897 50 mg Participants received a single dose of MEDI8897 50 mg intramuscularly.
Overall Study STARTED	18	8	31	32
Overall Study COMPLETED	16	8	31	30
Overall Study NOT COMPLETED	2	0	0	2

Reasons for withdrawal

Measure	Placebo Participants received placebo intramuscularly.	MEDI8897 10 mg Participants received a single dose of MEDI8897 10 milligram (mg) intramuscularly.	MEDI8897 25 mg Participants received a single dose of MEDI8897 25 mg intramuscularly.	MEDI8897 50 mg Participants received a single dose of MEDI8897 50 mg intramuscularly.
Overall Study Lost to Follow-up	0	0	0	1
Overall Study Withdrawal by Subject	1	0	0	0
Overall Study Other	1	0	0	1

Baseline Characteristics

A Phase 1b/2a Randomized, Double-Blind, Placebo-controlled, Dose-escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MEDI8897, a Monoclonal Antibody With an Extended Half-life Against Respiratory Syncytial Virus, in Healthy Preterm Infants

Baseline characteristics by cohort

Measure	Placebo n=18 Participants Participants received placebo intramuscularly.	MEDI8897 10 mg n=8 Participants Participants received a single dose of MEDI8897 10 milligram (mg) intramuscularly.	MEDI8897 25 mg n=31 Participants Participants received a single dose of MEDI8897 25 mg intramuscularly.	MEDI8897 50 mg n=32 Participants Participants received a single dose of MEDI8897 50 mg intramuscularly.	Total n=89 Participants Total of all reporting groups
Age, Continuous	7.0 Months STANDARD_DEVIATION 2.6 • n=5 Participants	4.2 Months STANDARD_DEVIATION 2.1 • n=7 Participants	6.7 Months STANDARD_DEVIATION 2.7 • n=5 Participants	6.9 Months STANDARD_DEVIATION 2.5 • n=4 Participants	6.6 Months STANDARD_DEVIATION 2.6 • n=21 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	4 Participants n=7 Participants	19 Participants n=5 Participants	19 Participants n=4 Participants	53 Participants n=21 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	4 Participants n=7 Participants	12 Participants n=5 Participants	13 Participants n=4 Participants	36 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	10 Participants n=5 Participants	1 Participants n=7 Participants	19 Participants n=5 Participants	21 Participants n=4 Participants	51 Participants n=21 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	6 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants	12 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	0 Participants n=7 Participants	11 Participants n=5 Participants	7 Participants n=4 Participants	22 Participants n=21 Participants

PRIMARY outcome

Timeframe: From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)

Population: The As-treated Population included all participants who received any study drug.

An adverse event (AE) is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. 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 situation (immediate risk of dying); persistent or significant disability/incapacity of a participant who received MEDI8897. TEAEs and TESAEs were the events that occurred between administration of study drug (Day 1) and Day 361 that were absent before treatment or that worsened relative to pre-treatment state.

Outcome measures

Measure	Placebo n=18 Participants Participants received placebo intramuscularly.	MEDI8897 10 mg n=8 Participants Participants received a single dose of MEDI8897 10 milligram (mg) intramuscularly.	MEDI8897 25 mg n=31 Participants Participants received a single dose of MEDI8897 25 mg intramuscularly.	MEDI8897 50 mg n=32 Participants Participants received a single dose of MEDI8897 50 mg intramuscularly.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) TEAEs	17 Participants	5 Participants	31 Participants	30 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) TESAEs	0 Participants	0 Participants	1 Participants	2 Participants

PRIMARY outcome

Timeframe: From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)

Population: The As-treated Population included all participants who received any study drug.

An AESI was one of scientific and medical interest specific to understanding of study product and may have required close monitoring and rapid communication by investigator (that is, within 24 hrs of knowledge of the event) to the sponsor. The AESIs for this study were hepatic function abnormality meeting the definition of Hy's law, hypersensitivity reactions including anaphylaxis, immune complex disease, and thrombocytopenia. Treatment-emergent AESIs were collected from the time of dosing until Day 361 post-dose.

Outcome measures

Measure	Placebo n=18 Participants Participants received placebo intramuscularly.	MEDI8897 10 mg n=8 Participants Participants received a single dose of MEDI8897 10 milligram (mg) intramuscularly.	MEDI8897 25 mg n=31 Participants Participants received a single dose of MEDI8897 25 mg intramuscularly.	MEDI8897 50 mg n=32 Participants Participants received a single dose of MEDI8897 50 mg intramuscularly.
Number of Participants With Treatment-Emergent Adverse Events of Special Interest	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: From Study Drug Administration (Day 1) Through the Follow-up Period (Day 151)

Population: The As-treated Population included all participants who received any study drug.

Laboratory abnormalities determined by the investigator to be clinically significant that occurred after study drug dosing through 151 days post-dose that were absent before treatment or that worsened relative to pre-treatment state were reported as TEAEs. Laboratory evaluations (haematology and serum chemistry) of blood samples were performed.

Outcome measures

Measure	Placebo n=18 Participants Participants received placebo intramuscularly.	MEDI8897 10 mg n=8 Participants Participants received a single dose of MEDI8897 10 milligram (mg) intramuscularly.	MEDI8897 25 mg n=31 Participants Participants received a single dose of MEDI8897 25 mg intramuscularly.	MEDI8897 50 mg n=32 Participants Participants received a single dose of MEDI8897 50 mg intramuscularly.
Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events Anaemia	6 Participants	0 Participants	8 Participants	4 Participants
Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events Microcytic anaemia	0 Participants	0 Participants	0 Participants	3 Participants
Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events Neutropenia	0 Participants	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose

Population: The As-treated Population included all participants who received any study drug. Here, "N" signifies number of participants analyzed for this outcome measure.

The Tmax defined as time at which maximum observed concentration of MEDI8897 (Cmax) was observed.

Outcome measures

Measure	Placebo n=5 Participants Participants received placebo intramuscularly.	MEDI8897 10 mg n=29 Participants Participants received a single dose of MEDI8897 10 milligram (mg) intramuscularly.	MEDI8897 25 mg n=31 Participants Participants received a single dose of MEDI8897 25 mg intramuscularly.	MEDI8897 50 mg Participants received a single dose of MEDI8897 50 mg intramuscularly.
Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI8897	7.04 Day Standard Deviation 0.0683	7.04 Day Standard Deviation 0.394	6.93 Day Standard Deviation 0.549	—

SECONDARY outcome

Timeframe: Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose

Population: The As-treated Population included all participants who received any study drug. Here, "N" signifies number of participants analyzed for this outcome measure.

The Cmax is the maximum observed serum concentration of MEDI8897.

Outcome measures

Measure	Placebo n=5 Participants Participants received placebo intramuscularly.	MEDI8897 10 mg n=29 Participants Participants received a single dose of MEDI8897 10 milligram (mg) intramuscularly.	MEDI8897 25 mg n=31 Participants Participants received a single dose of MEDI8897 25 mg intramuscularly.	MEDI8897 50 mg Participants received a single dose of MEDI8897 50 mg intramuscularly.
Maximum Observed Serum Concentration (Cmax) of MEDI8897	23.2 microgram per milliliter (mcg/mL) Standard Deviation 9.28	30.9 microgram per milliliter (mcg/mL) Standard Deviation 10.4	71.7 microgram per milliliter (mcg/mL) Standard Deviation 15.9	—

SECONDARY outcome

Timeframe: Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), and 150 (± 7) Post-dose

Population: The As-treated Population included all participants who received any study drug. Here, "N" signifies number of participants analyzed for this outcome measure.

Area under the concentration-time curve of the MEDI8897 in serum over the time interval from day 1 to day 151 (AUC1-151).

Outcome measures

Measure	Placebo n=5 Participants Participants received placebo intramuscularly.	MEDI8897 10 mg n=29 Participants Participants received a single dose of MEDI8897 10 milligram (mg) intramuscularly.	MEDI8897 25 mg n=31 Participants Participants received a single dose of MEDI8897 25 mg intramuscularly.	MEDI8897 50 mg Participants received a single dose of MEDI8897 50 mg intramuscularly.
Area Under the Concentration-Time Curve From Day 1 to Day 151 (AUC [1-151]) of MEDI8897	1940 Day*mcg/mL Standard Deviation 809	2260 Day*mcg/mL Standard Deviation 881	5470 Day*mcg/mL Standard Deviation 1440	—

SECONDARY outcome

Timeframe: Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose

Population: The As-treated Population included all participants who received any study drug. Here, "N" signifies number of participants analyzed for this outcome measure.

The pharmacokinetic (PK) parameter AUC (0-infinity) was estimated based on the serum concentrations of MEDI8897.

Outcome measures

Measure	Placebo n=1 Participants Participants received placebo intramuscularly.	MEDI8897 10 mg n=6 Participants Participants received a single dose of MEDI8897 10 milligram (mg) intramuscularly.	MEDI8897 25 mg n=14 Participants Participants received a single dose of MEDI8897 25 mg intramuscularly.	MEDI8897 50 mg Participants received a single dose of MEDI8897 50 mg intramuscularly.
Area Under the Concentration-Time Curve From Zero to Infinity (AUC [0-infinity]) of MEDI8897	2450 Day*mcg/mL Standard Deviation NA Standard Deviation was not evaluable due to insufficient numbers of participants.	4320 Day*mcg/mL Standard Deviation 1070	7510 Day*mcg/mL Standard Deviation 1870	—

SECONDARY outcome

Timeframe: Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose

Population: The As-treated Population included all participants who received any study drug. Here, "N" signifies number of participants analyzed for this outcome measure.

Terminal phase elimination half-life (t1/2) is the time required for half of the drug to be eliminated from the serum.

Outcome measures

Measure	Placebo n=1 Participants Participants received placebo intramuscularly.	MEDI8897 10 mg n=6 Participants Participants received a single dose of MEDI8897 10 milligram (mg) intramuscularly.	MEDI8897 25 mg n=14 Participants Participants received a single dose of MEDI8897 25 mg intramuscularly.	MEDI8897 50 mg Participants received a single dose of MEDI8897 50 mg intramuscularly.
Terminal Elimination Half Life (t1/2) of MEDI8897	72.9 Day Standard Deviation NA Standard Deviation was not evaluable due to insufficient numbers of participants.	66.2 Day Standard Deviation 7.83	62.5 Day Standard Deviation 9.35	—

SECONDARY outcome

Timeframe: Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose

Population: The As-treated Population included all participants who received any study drug. Here, "N" signifies number of participants analyzed for this outcome measure.

Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the body.

Outcome measures

Measure	Placebo n=1 Participants Participants received placebo intramuscularly.	MEDI8897 10 mg n=6 Participants Participants received a single dose of MEDI8897 10 milligram (mg) intramuscularly.	MEDI8897 25 mg n=14 Participants Participants received a single dose of MEDI8897 25 mg intramuscularly.	MEDI8897 50 mg Participants received a single dose of MEDI8897 50 mg intramuscularly.
Extravascular Clearance (CL/F) of MEDI8897	4.08 mL/day Standard Deviation NA Standard Deviation was not evaluable due to insufficient numbers of participants.	6.05 mL/day Standard Deviation 1.31	7.01 mL/day Standard Deviation 1.57	—

SECONDARY outcome

Timeframe: Pre-dose at Baseline (Days -7 to -1) and on Days 7 (± 1), 30 (± 5), 150 (± 7) and 360 (± 7) Post-dose

Population: The As-treated Population included all participants who received any study drug. Here, "N" signifies number of participants analyzed for this outcome measure.

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug.

Outcome measures

Measure	Placebo n=1 Participants Participants received placebo intramuscularly.	MEDI8897 10 mg n=6 Participants Participants received a single dose of MEDI8897 10 milligram (mg) intramuscularly.	MEDI8897 25 mg n=14 Participants Participants received a single dose of MEDI8897 25 mg intramuscularly.	MEDI8897 50 mg Participants received a single dose of MEDI8897 50 mg intramuscularly.
Extravascular Volume of Distribution (Vz/F) of MEDI8897	429 mL Standard Deviation NA Standard Deviation was not evaluable due to insufficient numbers of participants.	581 mL Standard Deviation 159	633 mL Standard Deviation 168	—

SECONDARY outcome

Timeframe: Pre-dose at Baseline (Days -7 to -1) and on Days 31, 151, and 361 Post-dose

Population: The As-treated Population included participants who received any study drug.

A participant was considered ADA-positive if the participant had a positive reading at any time point post baseline. Titers greater than or equal to 50 were considered positive.

Outcome measures

Measure	Placebo n=18 Participants Participants received placebo intramuscularly.	MEDI8897 10 mg n=8 Participants Participants received a single dose of MEDI8897 10 milligram (mg) intramuscularly.	MEDI8897 25 mg n=31 Participants Participants received a single dose of MEDI8897 25 mg intramuscularly.	MEDI8897 50 mg n=32 Participants Participants received a single dose of MEDI8897 50 mg intramuscularly.
Number of Participants Positive for Anti-Drug Antibodies to MEDI8897 Baseline	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Positive for Anti-Drug Antibodies to MEDI8897 Day 31	0 Participants	2 Participants	0 Participants	0 Participants
Number of Participants Positive for Anti-Drug Antibodies to MEDI8897 Day 151	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Positive for Anti-Drug Antibodies to MEDI8897 Day 361	0 Participants	1 Participants	7 Participants	10 Participants

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

MEDI8897 10 mg

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

MEDI8897 25 mg

Serious events: 1 serious events

Other events: 31 other events

Deaths: 0 deaths

MEDI8897 50 mg

Serious events: 2 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=18 participants at risk Participants received placebo intramuscularly.	MEDI8897 10 mg n=8 participants at risk Participants received a single dose of MEDI8897 10 milligram (mg) intramuscularly.	MEDI8897 25 mg n=31 participants at risk Participants received a single dose of MEDI8897 25 mg intramuscularly.	MEDI8897 50 mg n=32 participants at risk Participants received a single dose of MEDI8897 50 mg intramuscularly.
Infections and infestations Lower respiratory tract infection	0.00% 0/18 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	0.00% 0/8 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	3.2% 1/31 • Number of events 2 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	3.1% 1/32 • Number of events 1 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)
Nervous system disorders Febrile convulsion	0.00% 0/18 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	0.00% 0/8 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	0.00% 0/31 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	6.2% 2/32 • Number of events 2 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)

Other adverse events

Measure	Placebo n=18 participants at risk Participants received placebo intramuscularly.	MEDI8897 10 mg n=8 participants at risk Participants received a single dose of MEDI8897 10 milligram (mg) intramuscularly.	MEDI8897 25 mg n=31 participants at risk Participants received a single dose of MEDI8897 25 mg intramuscularly.	MEDI8897 50 mg n=32 participants at risk Participants received a single dose of MEDI8897 50 mg intramuscularly.
Blood and lymphatic system disorders Anaemia	33.3% 6/18 • Number of events 6 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	0.00% 0/8 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	25.8% 8/31 • Number of events 8 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	12.5% 4/32 • Number of events 4 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)
Gastrointestinal disorders Diarrhoea	11.1% 2/18 • Number of events 2 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	25.0% 2/8 • Number of events 2 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	19.4% 6/31 • Number of events 6 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	3.1% 1/32 • Number of events 1 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)
Gastrointestinal disorders Vomiting	0.00% 0/18 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	0.00% 0/8 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	6.5% 2/31 • Number of events 2 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	6.2% 2/32 • Number of events 2 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)
General disorders Pyrexia	16.7% 3/18 • Number of events 3 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	37.5% 3/8 • Number of events 5 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	25.8% 8/31 • Number of events 8 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	15.6% 5/32 • Number of events 6 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)
Infections and infestations Bronchiolitis	5.6% 1/18 • Number of events 1 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	37.5% 3/8 • Number of events 7 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	9.7% 3/31 • Number of events 3 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	18.8% 6/32 • Number of events 6 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)
Infections and infestations Candida nappy rash	5.6% 1/18 • Number of events 1 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	0.00% 0/8 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	29.0% 9/31 • Number of events 9 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	6.2% 2/32 • Number of events 5 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)
Infections and infestations Conjunctivitis	0.00% 0/18 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	0.00% 0/8 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	6.5% 2/31 • Number of events 2 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	12.5% 4/32 • Number of events 4 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)
Infections and infestations Gastroenteritis	22.2% 4/18 • Number of events 5 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	25.0% 2/8 • Number of events 3 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	35.5% 11/31 • Number of events 11 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	25.0% 8/32 • Number of events 11 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)
Infections and infestations Impetigo	11.1% 2/18 • Number of events 2 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	0.00% 0/8 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	6.5% 2/31 • Number of events 3 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	9.4% 3/32 • Number of events 3 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)
Infections and infestations Lower respiratory tract infection	16.7% 3/18 • Number of events 4 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	0.00% 0/8 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	12.9% 4/31 • Number of events 5 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	6.2% 2/32 • Number of events 2 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)
Infections and infestations Nasopharyngitis	11.1% 2/18 • Number of events 2 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	0.00% 0/8 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	0.00% 0/31 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	9.4% 3/32 • Number of events 3 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)
Infections and infestations Oral candidiasis	5.6% 1/18 • Number of events 1 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	0.00% 0/8 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	16.1% 5/31 • Number of events 6 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	15.6% 5/32 • Number of events 6 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)
Infections and infestations Otitis media	22.2% 4/18 • Number of events 4 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	37.5% 3/8 • Number of events 11 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	22.6% 7/31 • Number of events 11 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	15.6% 5/32 • Number of events 6 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)
Infections and infestations Otitis media acute	5.6% 1/18 • Number of events 1 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	0.00% 0/8 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	3.2% 1/31 • Number of events 1 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	9.4% 3/32 • Number of events 5 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)
Infections and infestations Pharyngitis	11.1% 2/18 • Number of events 2 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	12.5% 1/8 • Number of events 1 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	0.00% 0/31 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	3.1% 1/32 • Number of events 1 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)
Infections and infestations Upper respiratory tract infection	66.7% 12/18 • Number of events 26 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	50.0% 4/8 • Number of events 8 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	74.2% 23/31 • Number of events 47 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	68.8% 22/32 • Number of events 48 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)
Infections and infestations Viral rash	5.6% 1/18 • Number of events 1 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	0.00% 0/8 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	9.7% 3/31 • Number of events 3 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	3.1% 1/32 • Number of events 1 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)
Respiratory, thoracic and mediastinal disorders Cough	22.2% 4/18 • Number of events 4 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	12.5% 1/8 • Number of events 1 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	35.5% 11/31 • Number of events 11 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	18.8% 6/32 • Number of events 8 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)
Respiratory, thoracic and mediastinal disorders Nasal congestion	5.6% 1/18 • Number of events 2 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	37.5% 3/8 • Number of events 4 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	9.7% 3/31 • Number of events 3 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	6.2% 2/32 • Number of events 2 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)
Respiratory, thoracic and mediastinal disorders Nasal obstruction	11.1% 2/18 • Number of events 4 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	0.00% 0/8 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	19.4% 6/31 • Number of events 8 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	15.6% 5/32 • Number of events 5 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	16.7% 3/18 • Number of events 3 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	0.00% 0/8 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	29.0% 9/31 • Number of events 14 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	9.4% 3/32 • Number of events 3 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)
Skin and subcutaneous tissue disorders Dermatitis	0.00% 0/18 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	0.00% 0/8 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	3.2% 1/31 • Number of events 1 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	9.4% 3/32 • Number of events 3 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)
Skin and subcutaneous tissue disorders Dermatitis contact	5.6% 1/18 • Number of events 1 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	12.5% 1/8 • Number of events 1 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	12.9% 4/31 • Number of events 5 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	0.00% 0/32 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)
Skin and subcutaneous tissue disorders Dermatitis diaper	5.6% 1/18 • Number of events 1 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	12.5% 1/8 • Number of events 1 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	19.4% 6/31 • Number of events 6 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	12.5% 4/32 • Number of events 4 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)
Skin and subcutaneous tissue disorders Dry skin	16.7% 3/18 • Number of events 3 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	0.00% 0/8 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	12.9% 4/31 • Number of events 4 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	3.1% 1/32 • Number of events 1 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)
Skin and subcutaneous tissue disorders Eczema	16.7% 3/18 • Number of events 3 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	0.00% 0/8 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	25.8% 8/31 • Number of events 9 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	18.8% 6/32 • Number of events 7 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)
Skin and subcutaneous tissue disorders Rash	0.00% 0/18 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	12.5% 1/8 • Number of events 1 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	12.9% 4/31 • Number of events 4 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)	0.00% 0/32 • From Study Drug Administration (Day 1) Through the Follow-up Period (Day 361)

Additional Information

M. Pamela Griffin

MedImmune, LLC

Phone: 301-398-4095

Email: information.center@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER