Intranasal Challenge of Healthy Adults With Respiratory Syncytial Virus (RSV)

RSV infection defined as positive quantitative real-time RT-PCR (RSV-A only) sample for >= 2 consecutive days through 12 days post-RSV challenge. A sample was determined positive if log10 copies/ml >= limit of quantitation (LLOQ; 2.80 log10 copies/mL). RSV infection defined as positive DFA sample for >= 2 consecutive days through 12 days post-RSV challenge. RSV infection by any method included positive plaque assay culture sample for >=1 day through 12 days post-RSV challenge, or positive quantitative real-time RT-PCR (RSV-A only) sample for >= 2 consecutive days through 12 days post-RSV challenge, or positive DFA sample for >=2 consecutive days through 12 days post-RSV challenge.

RSV infection by plaque assay culture defined as positive sample for >= 1 day through 12 days post-RSV challenge.

RSV infection by plaque assay culture defined as positive sample for >= 2 consecutive days through 12 days post-RSV challenge.

RSV infection by plaque assay culture defined as positive sample for >= 1 day through 12 days post-RSV challenge. log10 pfu/mL = log10 plaque-forming unit per milliliter.

RSV infection by plaque assay culture defined as positive sample for >= 2 consecutive days through 12 days post-RSV challenge.

Duration of viral shedding defined as the number of days from the first sample positive by any assay (that is, plaque assay culture, quantitative real-time (RT-PCR), or direct fluorescent Antibody (DFA) to the last sample positive by any assay.

MEDI-557 serum concentrations were summarized by each sampling point [LLOQ for MEDI-557 concentration assay was 1.56 microgram per millilitre (μg/mL) for serum].

The Cmax is the maximum observed serum concentration of MEDI-557.

The Tmax is defined as actual sampling time to reach maximum observed MEDI-557 concentration.

Serum decay half-life is the time measured for the serum concentration to decrease by one half.

The AUC(0-t) is the area under the serum concentration-time curve from time zero to any time 't'.

The AUC (0-infinity) is the area under the serum concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.

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 blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state which is estimated by (D/AUC[0-infinity])*(AUMC[0-infinity])/AUC[0-infinity]) where D is the dose of study drug, AUMC(0-infinity) is the area under the first moment curve extrapolated to infinity and AUC(0-infinity) is the area under the serum concentration-time curve from time zero to infinite time.

Clearance (CL) is a quantitative measure of the rate at which a drug substance is removed from the body. The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by the serum Area Under the Serum Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]).

MEDI-557 nasal wash concentrations were summarized by each sampling point [LLOQ for MEDI-557 concentration assay was 20.00 nanogram per millilitre (ng/mL) for nasal wash].

The Cmax is the maximum observed nasal wash concentration of MEDI-557.

The Tmax is defined as actual sampling time to reach maximum observed MEDI-557 concentration.

The AUC(0-t) is the area under the nasal wash concentration-time curve from time zero to any time 't'.

Anti-drug antibodies in the participants blood sample were detected using a validated immunoassay. Antidrug antibodies to MEDI-557 were defined as a detectable antibody titer with a dilution value of 1:30 or greater.

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was 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 were events between first dose of study drug and Day 360 that were absent before treatment or that worsened relative to pretreatment state.

Vital signs included temperature, respiration rate, heart rate, blood pressure. Abnormal vital sign parameters included Cardiac Disorders (Bradycardia), Respiratory, Thoracic and Mediastinal Disorders (Tachypnoea, Hyperventilation, Hypopnoea). Participants with abnormalities in these vital Signs investigations recorded as AEs were reported.

Laboratory investigations included hematology, coagulation, serum chemistry and urinalysis parameters. Participants with abnormalities in these laboratory investigations recorded as AEs were reported.

Spirometry is a standardized assessment to evaluate lung function. Baseline values for spirometry is defined as the last measure prior to viral challenge. Spirometry assessments included percent predicted forced expiratory volume in 1 second (FEV1), FEV1/forced vital capacity (FVC), and forced expiratory flow (FEF) 25%-75% values.