Trial Outcomes & Findings for Intranasal Challenge of Healthy Adults With Respiratory Syncytial Virus (RSV) (NCT NCT01475305)

NCT ID: NCT01475305

Last Updated: 2017-07-21

Results Overview

RSV infection is defined as positive plaque assay culture sample for greater than or equal to (\>=) 1 day through 12 days post-RSV challenge. A sample was determined positive if log10 plaque-forming units per milliliter \[pfu/mL\] greater than or equal lower limit of quantitation (LLOQ; 1.69 log10 pfu/mL) and 2 of the 3 replicates must have greater than (\>) 0 pfu/mL.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

7 participants

Primary outcome timeframe

From Day 4 to Day 15

Results posted on

2017-07-21

Participant Flow

A total of 90 participants were screened, out of these, 7 participants were randomized and completed the study.

Participant milestones

Participant milestones
Measure
Placebo
Participants received single intravenous (IV) dose of placebo matched to MEDI-557 on Day 1 and were inoculated with respiratory syncytial virus (RSV-A) (Memphis-37 strain) as intranasal drops on Day 3.
MEDI-557
Participants received single IV dose of 30 milligram per kilogram (mg/kg) MEDI-557 on Day 1 and were inoculated with RSV-A (Memphis-37 strain) as intranasal drops on Day 3.
Overall Study
STARTED
4
3
Overall Study
End of Quarantine, Day 15
4
3
Overall Study
COMPLETED
4
3
Overall Study
NOT COMPLETED
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Placebo
n=4 Participants
Participants received single intravenous (IV) dose of placebo matched to MEDI-557 on Day 1 and were inoculated with respiratory syncytial virus (RSV-A) (Memphis-37 strain) as intranasal drops on Day 3.
MEDI-557
n=3 Participants
Participants received single IV dose of 30 milligram per kilogram (mg/kg) MEDI-557 on Day 1 and were inoculated with RSV-A (Memphis-37 strain) as intranasal drops on Day 3.
Total
n=7 Participants
Total of all reporting groups
Age, Continuous
24.5 Years
STANDARD_DEVIATION 4.4 • n=5 Participants
28.0 Years
STANDARD_DEVIATION 9.5 • n=7 Participants
26.0 Years
STANDARD_DEVIATION 6.6 • n=5 Participants
Sex: Female, Male
Female
0 Participants
n=5 Participants
2 Participants
n=7 Participants
2 Participants
n=5 Participants
Sex: Female, Male
Male
4 Participants
n=5 Participants
1 Participants
n=7 Participants
5 Participants
n=5 Participants

PRIMARY outcome

Timeframe: From Day 4 to Day 15

Population: Population for RSV Incidence included all participants who received both the investigational product and RSV challenge.

RSV infection is defined as positive plaque assay culture sample for greater than or equal to (\>=) 1 day through 12 days post-RSV challenge. A sample was determined positive if log10 plaque-forming units per milliliter \[pfu/mL\] greater than or equal lower limit of quantitation (LLOQ; 1.69 log10 pfu/mL) and 2 of the 3 replicates must have greater than (\>) 0 pfu/mL.

Outcome measures

Outcome measures
Measure
Placebo
n=3 Participants
Participants received single intravenous (IV) dose of placebo matched to MEDI-557 on Day 1 and were inoculated with respiratory syncytial virus (RSV-A) (Memphis-37 strain) as intranasal drops on Day 3.
MEDI-557
n=3 Participants
Participants received single IV dose of 30 milligram per kilogram (mg/kg) MEDI-557 on Day 1 and were inoculated with RSV-A (Memphis-37 strain) as intranasal drops on Day 3.
Percentage of Participants Developing Respiratory Syncytial Virus (RSV) Infection Post-RSV Challenge Measured by Plaque Assay Culture
66.7 percentage of participants
0.0 percentage of participants

SECONDARY outcome

Timeframe: From Day 4 to Day 15

Population: Population for RSV Incidence included all participants who received both the investigational product and RSV challenge.

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.

Outcome measures

Outcome measures
Measure
Placebo
n=3 Participants
Participants received single intravenous (IV) dose of placebo matched to MEDI-557 on Day 1 and were inoculated with respiratory syncytial virus (RSV-A) (Memphis-37 strain) as intranasal drops on Day 3.
MEDI-557
n=3 Participants
Participants received single IV dose of 30 milligram per kilogram (mg/kg) MEDI-557 on Day 1 and were inoculated with RSV-A (Memphis-37 strain) as intranasal drops on Day 3.
Percentage of Participants Developing Respiratory Syncytial Virus (RSV) Infection Post-RSV Challenge Measured by Quantitative Real-Time Reverse Transcriptase Polymerase Chain Reaction (RT-PCR), Direct Fluorescent Antibody (DFA), And by Any Method
RSV infection by quantitative real-time RT-PCR
66.7 percentage of participants
66.7 percentage of participants
Percentage of Participants Developing Respiratory Syncytial Virus (RSV) Infection Post-RSV Challenge Measured by Quantitative Real-Time Reverse Transcriptase Polymerase Chain Reaction (RT-PCR), Direct Fluorescent Antibody (DFA), And by Any Method
RSV infection by DFA
66.7 percentage of participants
0.0 percentage of participants
Percentage of Participants Developing Respiratory Syncytial Virus (RSV) Infection Post-RSV Challenge Measured by Quantitative Real-Time Reverse Transcriptase Polymerase Chain Reaction (RT-PCR), Direct Fluorescent Antibody (DFA), And by Any Method
RSV infection by Any Method
66.7 percentage of participants
66.7 percentage of participants

SECONDARY outcome

Timeframe: From Day 5 through Day 31

Population: Population for RSV Plaque Assay Culture Virology included all participants who received both investigational product and RSV challenge and were positive for RSV 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 \>= 1 day through 12 days post-RSV challenge.

Outcome measures

Outcome measures
Measure
Placebo
n=2 Participants
Participants received single intravenous (IV) dose of placebo matched to MEDI-557 on Day 1 and were inoculated with respiratory syncytial virus (RSV-A) (Memphis-37 strain) as intranasal drops on Day 3.
MEDI-557
Participants received single IV dose of 30 milligram per kilogram (mg/kg) MEDI-557 on Day 1 and were inoculated with RSV-A (Memphis-37 strain) as intranasal drops on Day 3.
Mean Viral Load AUC0-t by Plaque Assay Culture
42.165 log10 pfu*day/mL
Standard Deviation 3.305

SECONDARY outcome

Timeframe: From Day 5 through Day 31

Population: Population for RSV Quantitative Real-Time RT-PCR Virology included all participants who received both the investigational product and RSV challenge and were positive for RSV-A by quantitative real-time RT-PCR (defined as positive samples for \>= 2 consecutive days 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.

Outcome measures

Outcome measures
Measure
Placebo
n=2 Participants
Participants received single intravenous (IV) dose of placebo matched to MEDI-557 on Day 1 and were inoculated with respiratory syncytial virus (RSV-A) (Memphis-37 strain) as intranasal drops on Day 3.
MEDI-557
n=2 Participants
Participants received single IV dose of 30 milligram per kilogram (mg/kg) MEDI-557 on Day 1 and were inoculated with RSV-A (Memphis-37 strain) as intranasal drops on Day 3.
Mean Viral Load AUC0-t by Realtime Reverse Transcriptase Polymerase Chain Reaction (RT-PCR)
100.04 log10 copies*day/mL
Standard Deviation 7.000
65.708 log10 copies*day/mL
Standard Deviation 1.488

SECONDARY outcome

Timeframe: From Day 5 through Day 31

Population: Population for RSV Plaque Assay Culture Virology included all participants who received both investigational product and RSV challenge and were positive for RSV 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 \>= 1 day through 12 days post-RSV challenge. log10 pfu/mL = log10 plaque-forming unit per milliliter.

Outcome measures

Outcome measures
Measure
Placebo
n=2 Participants
Participants received single intravenous (IV) dose of placebo matched to MEDI-557 on Day 1 and were inoculated with respiratory syncytial virus (RSV-A) (Memphis-37 strain) as intranasal drops on Day 3.
MEDI-557
Participants received single IV dose of 30 milligram per kilogram (mg/kg) MEDI-557 on Day 1 and were inoculated with RSV-A (Memphis-37 strain) as intranasal drops on Day 3.
Mean Nasal RSV Peak as Measured by Plaque Assay Culture
4.150 log10 pfu/mL
Standard Deviation 0.521

SECONDARY outcome

Timeframe: From Day 5 through Day 31

Population: Population for RSV Quantitative Real-Time RT-PCR Virology included all participants who received both the investigational product and RSV challenge and were positive for RSV-A by quantitative real-time RT-PCR (defined as positive samples for \>= 2 consecutive days 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.

Outcome measures

Outcome measures
Measure
Placebo
n=2 Participants
Participants received single intravenous (IV) dose of placebo matched to MEDI-557 on Day 1 and were inoculated with respiratory syncytial virus (RSV-A) (Memphis-37 strain) as intranasal drops on Day 3.
MEDI-557
n=2 Participants
Participants received single IV dose of 30 milligram per kilogram (mg/kg) MEDI-557 on Day 1 and were inoculated with RSV-A (Memphis-37 strain) as intranasal drops on Day 3.
Mean Nasal RSV Peak as Measured by Quantitative Realtime Reverse Transcriptase Polymerase Chain Reaction (RT-PCR)
7.700 log10 copies/mL
Standard Deviation 0.453
4.260 log10 copies/mL
Standard Deviation 0.863

SECONDARY outcome

Timeframe: From Day 5 through Day 31

Population: Population for RSV Incidence by any Viral Assay included all participants who received both the investigational product and RSV challenge and were positive for RSV by plaque assay culture, quantitative real-time RT-PCR, or DFA.

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.

Outcome measures

Outcome measures
Measure
Placebo
n=2 Participants
Participants received single intravenous (IV) dose of placebo matched to MEDI-557 on Day 1 and were inoculated with respiratory syncytial virus (RSV-A) (Memphis-37 strain) as intranasal drops on Day 3.
MEDI-557
n=2 Participants
Participants received single IV dose of 30 milligram per kilogram (mg/kg) MEDI-557 on Day 1 and were inoculated with RSV-A (Memphis-37 strain) as intranasal drops on Day 3.
Duration of Respiratory Syncytial Virus (RSV) Viral Shedding
10.0 days
Full Range 0.0 • Interval 10.0 to 10.0
6.5 days
Full Range 4.5 • Interval 2.0 to 11.0

SECONDARY outcome

Timeframe: Pre-dose (Day 1); 1,4 and 8 hours post-dose on Day 1 and post-dose on Days 2, 3, 5, 7, 9, 11, 15, 31, 61, 91, 120, 150, 180, 240, 300 and 360

Population: Population for PK included all participants who received a full dose of investigational product and had \>= 1 post-baseline measurement for PK. Here n = participants evaluable for specified categories, for each arm, respectively.

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

Outcome measures

Outcome measures
Measure
Placebo
n=3 Participants
Participants received single intravenous (IV) dose of placebo matched to MEDI-557 on Day 1 and were inoculated with respiratory syncytial virus (RSV-A) (Memphis-37 strain) as intranasal drops on Day 3.
MEDI-557
Participants received single IV dose of 30 milligram per kilogram (mg/kg) MEDI-557 on Day 1 and were inoculated with RSV-A (Memphis-37 strain) as intranasal drops on Day 3.
Mean Serum MEDI-557 Concentration Through Day 360
Day 1 (pre-dose) (n=3)
0.000 microgram per milliliter (ug/mL)
Standard Deviation 0.000
Mean Serum MEDI-557 Concentration Through Day 360
1 hr Post-dose (n=3)
498.730 microgram per milliliter (ug/mL)
Standard Deviation 6.615
Mean Serum MEDI-557 Concentration Through Day 360
4 hr Post-dose (n=3)
462.937 microgram per milliliter (ug/mL)
Standard Deviation 40.212
Mean Serum MEDI-557 Concentration Through Day 360
8 hr Post-dose (n=3)
458.413 microgram per milliliter (ug/mL)
Standard Deviation 40.613
Mean Serum MEDI-557 Concentration Through Day 360
Day 2 (n=3)
407.627 microgram per milliliter (ug/mL)
Standard Deviation 13.420
Mean Serum MEDI-557 Concentration Through Day 360
Day 3 (n=3)
343.283 microgram per milliliter (ug/mL)
Standard Deviation 48.078
Mean Serum MEDI-557 Concentration Through Day 360
Day 5 (n=3)
298.020 microgram per milliliter (ug/mL)
Standard Deviation 48.966
Mean Serum MEDI-557 Concentration Through Day 360
Day 7 (n=3)
287.917 microgram per milliliter (ug/mL)
Standard Deviation 39.276
Mean Serum MEDI-557 Concentration Through Day 360
Day 9 (n=3)
293.897 microgram per milliliter (ug/mL)
Standard Deviation 33.128
Mean Serum MEDI-557 Concentration Through Day 360
Day 11(n=3)
265.107 microgram per milliliter (ug/mL)
Standard Deviation 24.076
Mean Serum MEDI-557 Concentration Through Day 360
Day 15 (n=3)
252.327 microgram per milliliter (ug/mL)
Standard Deviation 16.091
Mean Serum MEDI-557 Concentration Through Day 360
Day 31 (n=3)
252.177 microgram per milliliter (ug/mL)
Standard Deviation 23.225
Mean Serum MEDI-557 Concentration Through Day 360
Day 61 (n=2)
180.505 microgram per milliliter (ug/mL)
Standard Deviation 6.442
Mean Serum MEDI-557 Concentration Through Day 360
Day 91 (n=3)
131.053 microgram per milliliter (ug/mL)
Standard Deviation 4.571
Mean Serum MEDI-557 Concentration Through Day 360
Day 120 (n=3)
106.040 microgram per milliliter (ug/mL)
Standard Deviation 10.023
Mean Serum MEDI-557 Concentration Through Day 360
Day 150 (n=3)
75.583 microgram per milliliter (ug/mL)
Standard Deviation 11.258
Mean Serum MEDI-557 Concentration Through Day 360
Day 180 (n=3)
65.443 microgram per milliliter (ug/mL)
Standard Deviation 5.897
Mean Serum MEDI-557 Concentration Through Day 360
Day 240 (n=2)
43.875 microgram per milliliter (ug/mL)
Standard Deviation 6.428
Mean Serum MEDI-557 Concentration Through Day 360
Day 300 (n=3)
31.353 microgram per milliliter (ug/mL)
Standard Deviation 5.731
Mean Serum MEDI-557 Concentration Through Day 360
Day 360 (n=3)
20.343 microgram per milliliter (ug/mL)
Standard Deviation 4.138

SECONDARY outcome

Timeframe: Pre-dose (Day 1); 1,4 and 8 hours post-dose on Day 1 and post-dose on Days 2, 3, 5, 7, 9, 11, 15, 31, 61, 91, 120, 150, 180, 240, 300 and 360

Population: Population for PK included all participants who received a full dose of investigational product and had \>= 1 post-baseline measurement for PK.

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

Outcome measures

Outcome measures
Measure
Placebo
n=3 Participants
Participants received single intravenous (IV) dose of placebo matched to MEDI-557 on Day 1 and were inoculated with respiratory syncytial virus (RSV-A) (Memphis-37 strain) as intranasal drops on Day 3.
MEDI-557
Participants received single IV dose of 30 milligram per kilogram (mg/kg) MEDI-557 on Day 1 and were inoculated with RSV-A (Memphis-37 strain) as intranasal drops on Day 3.
Maximum Serum Concentration (Cmax) of MEDI-557
504.0433 microgram per milliliter (mcg/ml)
Standard Deviation 6.6189

SECONDARY outcome

Timeframe: Pre-dose (Day 1); 1,4 and 8 hours post-dose on Day 1 and post-dose on Days 2, 3, 5, 7, 9, 11, 15, 31, 61, 91, 120, 150, 180, 240, 300 and 360

Population: Population for PK included all participants who received a full dose of investigational product and had \>= 1 post-baseline measurement for PK.

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

Outcome measures

Outcome measures
Measure
Placebo
n=3 Participants
Participants received single intravenous (IV) dose of placebo matched to MEDI-557 on Day 1 and were inoculated with respiratory syncytial virus (RSV-A) (Memphis-37 strain) as intranasal drops on Day 3.
MEDI-557
Participants received single IV dose of 30 milligram per kilogram (mg/kg) MEDI-557 on Day 1 and were inoculated with RSV-A (Memphis-37 strain) as intranasal drops on Day 3.
Time to Reach Maximum Serum Concentration (Tmax) of MEDI-557
0.162 Day
Standard Deviation 0.068

SECONDARY outcome

Timeframe: Pre-dose (Day 1); 1,4 and 8 hours post-dose on Day 1 and post-dose on Days 2, 3, 5, 7, 9, 11, 15, 31, 61, 91, 120, 150, 180, 240, 300 and 360

Population: Population for PK included all participants who received a full dose of investigational product and had \>= 1 post-baseline measurement for PK.

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

Outcome measures

Outcome measures
Measure
Placebo
n=3 Participants
Participants received single intravenous (IV) dose of placebo matched to MEDI-557 on Day 1 and were inoculated with respiratory syncytial virus (RSV-A) (Memphis-37 strain) as intranasal drops on Day 3.
MEDI-557
Participants received single IV dose of 30 milligram per kilogram (mg/kg) MEDI-557 on Day 1 and were inoculated with RSV-A (Memphis-37 strain) as intranasal drops on Day 3.
Serum Half Life (t1/2) of MEDI-557
94.0029426 Day
Standard Deviation 93.8412056

SECONDARY outcome

Timeframe: Pre-dose (Day 1); 1,4 and 8 hours post-dose on Day 1 and post-dose on Days 2, 3, 5, 7, 9, 11, 15, 31, 61, 91, 120, 150, 180, 240, 300 and 360

Population: Population for PK included all participants who received a full dose of investigational product and had \>= 1 post-baseline measurement for PK.

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

Outcome measures

Outcome measures
Measure
Placebo
n=3 Participants
Participants received single intravenous (IV) dose of placebo matched to MEDI-557 on Day 1 and were inoculated with respiratory syncytial virus (RSV-A) (Memphis-37 strain) as intranasal drops on Day 3.
MEDI-557
Participants received single IV dose of 30 milligram per kilogram (mg/kg) MEDI-557 on Day 1 and were inoculated with RSV-A (Memphis-37 strain) as intranasal drops on Day 3.
Area Under the Serum Concentration-Time Curve From Time Zero to Time 't' (AUC[0-t]) of MEDI-557
34484.8642 day*microgram per milliliter (d*mcg/ml)
Standard Deviation 1114.4471

SECONDARY outcome

Timeframe: Pre-dose (Day 1); 1,4 and 8 hours post-dose on Day 1 and post-dose on Days 2, 3, 5, 7, 9, 11, 15, 31, 61, 91, 120, 150, 180, 240, 300 and 360

Population: Population for PK included all participants who received a full dose of investigational product and had \>= 1 post-baseline measurement for PK.

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.

Outcome measures

Outcome measures
Measure
Placebo
n=3 Participants
Participants received single intravenous (IV) dose of placebo matched to MEDI-557 on Day 1 and were inoculated with respiratory syncytial virus (RSV-A) (Memphis-37 strain) as intranasal drops on Day 3.
MEDI-557
Participants received single IV dose of 30 milligram per kilogram (mg/kg) MEDI-557 on Day 1 and were inoculated with RSV-A (Memphis-37 strain) as intranasal drops on Day 3.
Area Under the Serum Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of MEDI-557
37266.5740 d*mcg/ml
Standard Deviation 1764.7070

SECONDARY outcome

Timeframe: Pre-dose (Day 1); 1,4 and 8 hours post-dose on Day 1 and post-dose on Days 2, 3, 5, 7, 9, 11, 15, 31, 61, 91, 120, 150, 180, 240, 300 and 360

Population: Population for PK included all participants who received a full dose of investigational product and had \>= 1 post-baseline measurement for PK.

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.

Outcome measures

Outcome measures
Measure
Placebo
n=3 Participants
Participants received single intravenous (IV) dose of placebo matched to MEDI-557 on Day 1 and were inoculated with respiratory syncytial virus (RSV-A) (Memphis-37 strain) as intranasal drops on Day 3.
MEDI-557
Participants received single IV dose of 30 milligram per kilogram (mg/kg) MEDI-557 on Day 1 and were inoculated with RSV-A (Memphis-37 strain) as intranasal drops on Day 3.
Volume of Distribution at Steady-State (Vss) of MEDI-557
6644.3433 milliliter (ml)
Standard Deviation 606.4269

SECONDARY outcome

Timeframe: Pre-dose (Day 1); 1,4 and 8 hours post-dose on Day 1 and post-dose on Days 2, 3, 5, 7, 9, 11, 15, 31, 61, 91, 120, 150, 180, 240, 300 and 360

Population: Population for PK included all participants who received a full dose of investigational product and had \>= 1 post-baseline measurement for PK.

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\[0-infinity\]).

Outcome measures

Outcome measures
Measure
Placebo
n=3 Participants
Participants received single intravenous (IV) dose of placebo matched to MEDI-557 on Day 1 and were inoculated with respiratory syncytial virus (RSV-A) (Memphis-37 strain) as intranasal drops on Day 3.
MEDI-557
Participants received single IV dose of 30 milligram per kilogram (mg/kg) MEDI-557 on Day 1 and were inoculated with RSV-A (Memphis-37 strain) as intranasal drops on Day 3.
Mean Clearance of MEDI-557
50.3831 milliliter per day (ml/d)
Standard Deviation 4.6158

SECONDARY outcome

Timeframe: Pre-dose (Day 1) and post-dose on Days 2, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, and 31

Population: Population for PK included all participants who received a full dose of investigational product and had \>= 1 post-baseline measurement for PK.

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

Outcome measures

Outcome measures
Measure
Placebo
n=3 Participants
Participants received single intravenous (IV) dose of placebo matched to MEDI-557 on Day 1 and were inoculated with respiratory syncytial virus (RSV-A) (Memphis-37 strain) as intranasal drops on Day 3.
MEDI-557
Participants received single IV dose of 30 milligram per kilogram (mg/kg) MEDI-557 on Day 1 and were inoculated with RSV-A (Memphis-37 strain) as intranasal drops on Day 3.
Mean Nasal Wash Concentration of MEDI-557 at Respective Time-Points
Day 1 (pre-dose)
0.000 nanogram per milliliter (ng/mL)
Standard Deviation 0.000
Mean Nasal Wash Concentration of MEDI-557 at Respective Time-Points
Day 2
166.613 nanogram per milliliter (ng/mL)
Standard Deviation 8.257
Mean Nasal Wash Concentration of MEDI-557 at Respective Time-Points
Day 5
192.827 nanogram per milliliter (ng/mL)
Standard Deviation 160.257
Mean Nasal Wash Concentration of MEDI-557 at Respective Time-Points
Day 6
189.767 nanogram per milliliter (ng/mL)
Standard Deviation 87.745
Mean Nasal Wash Concentration of MEDI-557 at Respective Time-Points
Day 7
227.980 nanogram per milliliter (ng/mL)
Standard Deviation 189.806
Mean Nasal Wash Concentration of MEDI-557 at Respective Time-Points
Day 8
308.153 nanogram per milliliter (ng/mL)
Standard Deviation 173.823
Mean Nasal Wash Concentration of MEDI-557 at Respective Time-Points
Day 9
201.647 nanogram per milliliter (ng/mL)
Standard Deviation 105.288
Mean Nasal Wash Concentration of MEDI-557 at Respective Time-Points
Day 10
132.407 nanogram per milliliter (ng/mL)
Standard Deviation 134.702
Mean Nasal Wash Concentration of MEDI-557 at Respective Time-Points
Day 11
220.953 nanogram per milliliter (ng/mL)
Standard Deviation 58.505
Mean Nasal Wash Concentration of MEDI-557 at Respective Time-Points
Day 12
262.800 nanogram per milliliter (ng/mL)
Standard Deviation 310.692
Mean Nasal Wash Concentration of MEDI-557 at Respective Time-Points
Day 13
89.867 nanogram per milliliter (ng/mL)
Standard Deviation 72.249
Mean Nasal Wash Concentration of MEDI-557 at Respective Time-Points
Day 14
184.747 nanogram per milliliter (ng/mL)
Standard Deviation 260.718
Mean Nasal Wash Concentration of MEDI-557 at Respective Time-Points
Day 15
243.567 nanogram per milliliter (ng/mL)
Standard Deviation 251.884
Mean Nasal Wash Concentration of MEDI-557 at Respective Time-Points
Day 31
62.707 nanogram per milliliter (ng/mL)
Standard Deviation 62.348

SECONDARY outcome

Timeframe: Pre-dose (Day 1) and post-dose on Days 2, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, and 31

Population: Population for PK included all participants who received a full dose of investigational product and had \>= 1 post-baseline measurement for PK.

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

Outcome measures

Outcome measures
Measure
Placebo
n=3 Participants
Participants received single intravenous (IV) dose of placebo matched to MEDI-557 on Day 1 and were inoculated with respiratory syncytial virus (RSV-A) (Memphis-37 strain) as intranasal drops on Day 3.
MEDI-557
Participants received single IV dose of 30 milligram per kilogram (mg/kg) MEDI-557 on Day 1 and were inoculated with RSV-A (Memphis-37 strain) as intranasal drops on Day 3.
Maximum Nasal Wash Concentration (Cmax) of MEDI-557
377.9800 nanogram per milliliter (ng/ml)
Standard Deviation 212.2542

SECONDARY outcome

Timeframe: Pre-dose (Day 1) and post-dose on Days 2, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, and 31

Population: Population for PK included all participants who received a full dose of investigational product and had \>= 1 post-baseline measurement for PK.

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

Outcome measures

Outcome measures
Measure
Placebo
n=3 Participants
Participants received single intravenous (IV) dose of placebo matched to MEDI-557 on Day 1 and were inoculated with respiratory syncytial virus (RSV-A) (Memphis-37 strain) as intranasal drops on Day 3.
MEDI-557
Participants received single IV dose of 30 milligram per kilogram (mg/kg) MEDI-557 on Day 1 and were inoculated with RSV-A (Memphis-37 strain) as intranasal drops on Day 3.
Time to Reach Maximum Nasal Wash Concentration (Tmax) of MEDI-557
9.051 Day
Standard Deviation 2.113

SECONDARY outcome

Timeframe: Pre-dose (Day 1) and post-dose on Days 2, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, and 31

Population: Population for PK included all participants who received a full dose of investigational product and had \>= 1 post-baseline measurement for PK.

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

Outcome measures

Outcome measures
Measure
Placebo
n=3 Participants
Participants received single intravenous (IV) dose of placebo matched to MEDI-557 on Day 1 and were inoculated with respiratory syncytial virus (RSV-A) (Memphis-37 strain) as intranasal drops on Day 3.
MEDI-557
Participants received single IV dose of 30 milligram per kilogram (mg/kg) MEDI-557 on Day 1 and were inoculated with RSV-A (Memphis-37 strain) as intranasal drops on Day 3.
Area Under the Nasal Wash Concentration-Time Curve From Time Zero to Time 't' (AUC[0-t]) of MEDI-557
4541.3636 day*nanogram per milliliter (d*ng/ml)
Standard Deviation 3905.7874

SECONDARY outcome

Timeframe: Day 1 (pre-dose); Day 31, 91, 150, 180, 240, 300 and 360 post-dose

Population: Population for ADA included all participants who received any amount of investigational product and had \>= 1 post-baseline measurement for ADA. Here, "n" is number of participants analysed at specific time point.

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.

Outcome measures

Outcome measures
Measure
Placebo
n=4 Participants
Participants received single intravenous (IV) dose of placebo matched to MEDI-557 on Day 1 and were inoculated with respiratory syncytial virus (RSV-A) (Memphis-37 strain) as intranasal drops on Day 3.
MEDI-557
n=3 Participants
Participants received single IV dose of 30 milligram per kilogram (mg/kg) MEDI-557 on Day 1 and were inoculated with RSV-A (Memphis-37 strain) as intranasal drops on Day 3.
Percentage of Participants With Positive Anti-MEDI-557 Antibodies
Day 1 (pre-dose) (n=4,3)
0 percentage of participants
0 percentage of participants
Percentage of Participants With Positive Anti-MEDI-557 Antibodies
Day 31 (n=4,3)
0 percentage of participants
0 percentage of participants
Percentage of Participants With Positive Anti-MEDI-557 Antibodies
Day 91 (n=4,3)
0 percentage of participants
0 percentage of participants
Percentage of Participants With Positive Anti-MEDI-557 Antibodies
Day 150 (n=3,3)
0 percentage of participants
33.3 percentage of participants
Percentage of Participants With Positive Anti-MEDI-557 Antibodies
Day 180 (n=4,3)
0 percentage of participants
66.7 percentage of participants
Percentage of Participants With Positive Anti-MEDI-557 Antibodies
Day 240 (n=3,2)
0 percentage of participants
50.0 percentage of participants
Percentage of Participants With Positive Anti-MEDI-557 Antibodies
Day 300 (n=4,3)
0 percentage of participants
33.3 percentage of participants
Percentage of Participants With Positive Anti-MEDI-557 Antibodies
Day 360 (n=4,3)
0 percentage of participants
0 percentage of participants

SECONDARY outcome

Timeframe: From Day 1 (immediately following administration of study drug) to Day 360

Population: Safety Population included all participants who received any amount of investigational product.

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.

Outcome measures

Outcome measures
Measure
Placebo
n=4 Participants
Participants received single intravenous (IV) dose of placebo matched to MEDI-557 on Day 1 and were inoculated with respiratory syncytial virus (RSV-A) (Memphis-37 strain) as intranasal drops on Day 3.
MEDI-557
n=3 Participants
Participants received single IV dose of 30 milligram per kilogram (mg/kg) MEDI-557 on Day 1 and were inoculated with RSV-A (Memphis-37 strain) as intranasal drops on Day 3.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
TEAEs
1 participants
0 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
TESAEs
4 participants
3 participants

SECONDARY outcome

Timeframe: From Day 1 through Day 31

Population: Safety Population included all participants who received any amount of investigational product.

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.

Outcome measures

Outcome measures
Measure
Placebo
n=4 Participants
Participants received single intravenous (IV) dose of placebo matched to MEDI-557 on Day 1 and were inoculated with respiratory syncytial virus (RSV-A) (Memphis-37 strain) as intranasal drops on Day 3.
MEDI-557
n=3 Participants
Participants received single IV dose of 30 milligram per kilogram (mg/kg) MEDI-557 on Day 1 and were inoculated with RSV-A (Memphis-37 strain) as intranasal drops on Day 3.
Number of Participants With Vital Signs Abnormalities Reported as Adverse Events (AEs)
3 participants
3 participants

SECONDARY outcome

Timeframe: From Day 1 through Day 91

Population: Safety Population included all participants who received any amount of investigational product.

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

Outcome measures

Outcome measures
Measure
Placebo
n=4 Participants
Participants received single intravenous (IV) dose of placebo matched to MEDI-557 on Day 1 and were inoculated with respiratory syncytial virus (RSV-A) (Memphis-37 strain) as intranasal drops on Day 3.
MEDI-557
n=3 Participants
Participants received single IV dose of 30 milligram per kilogram (mg/kg) MEDI-557 on Day 1 and were inoculated with RSV-A (Memphis-37 strain) as intranasal drops on Day 3.
Number of Participants With Abnormalities in Laboratory Investigations Reported as Adverse Events (AEs)
Hematology
0 participants
0 participants
Number of Participants With Abnormalities in Laboratory Investigations Reported as Adverse Events (AEs)
Coagulation
0 participants
0 participants
Number of Participants With Abnormalities in Laboratory Investigations Reported as Adverse Events (AEs)
Serum chemistry
0 participants
2 participants
Number of Participants With Abnormalities in Laboratory Investigations Reported as Adverse Events (AEs)
Urinalysis
0 participants
2 participants
Number of Participants With Abnormalities in Laboratory Investigations Reported as Adverse Events (AEs)
Cardiac enzymes
1 participants
0 participants

SECONDARY outcome

Timeframe: Days 1, 2, 3 (Baseline), 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 31

Population: Safety Population included all participants who received any amount of investigational product.

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.

Outcome measures

Outcome measures
Measure
Placebo
n=4 Participants
Participants received single intravenous (IV) dose of placebo matched to MEDI-557 on Day 1 and were inoculated with respiratory syncytial virus (RSV-A) (Memphis-37 strain) as intranasal drops on Day 3.
MEDI-557
n=3 Participants
Participants received single IV dose of 30 milligram per kilogram (mg/kg) MEDI-557 on Day 1 and were inoculated with RSV-A (Memphis-37 strain) as intranasal drops on Day 3.
Number of Participants With Clinically Meaningful Changes From Baseline in Spirometry Values
0 participants
0 participants

Adverse Events

Placebo

Serious events: 1 serious events
Other events: 4 other events
Deaths: 0 deaths

MEDI-557

Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Placebo
n=4 participants at risk
Participants received single intravenous (IV) dose of placebo matched to MEDI-557 on Day 1 and were inoculated with respiratory syncytial virus (RSV-A) (Memphis-37 strain) as intranasal drops on Day 3.
MEDI-557
n=3 participants at risk
Participants received single IV dose of 30 milligram per kilogram (mg/kg) MEDI-557 on Day 1 and were inoculated with RSV-A (Memphis-37 strain) as intranasal drops on Day 3.
Musculoskeletal and connective tissue disorders
Rhabdomyolysis
25.0%
1/4 • Number of events 1 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
0.00%
0/3 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.

Other adverse events

Other adverse events
Measure
Placebo
n=4 participants at risk
Participants received single intravenous (IV) dose of placebo matched to MEDI-557 on Day 1 and were inoculated with respiratory syncytial virus (RSV-A) (Memphis-37 strain) as intranasal drops on Day 3.
MEDI-557
n=3 participants at risk
Participants received single IV dose of 30 milligram per kilogram (mg/kg) MEDI-557 on Day 1 and were inoculated with RSV-A (Memphis-37 strain) as intranasal drops on Day 3.
Blood and lymphatic system disorders
Lymphadenopathy
25.0%
1/4 • Number of events 1 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
0.00%
0/3 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
Cardiac disorders
Bradycardia
25.0%
1/4 • Number of events 2 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
0.00%
0/3 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
Gastrointestinal disorders
Constipation
25.0%
1/4 • Number of events 1 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
0.00%
0/3 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
Gastrointestinal disorders
Gingival pain
25.0%
1/4 • Number of events 1 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
0.00%
0/3 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
Gastrointestinal disorders
Lip dry
25.0%
1/4 • Number of events 1 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
0.00%
0/3 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
Gastrointestinal disorders
Toothache
25.0%
1/4 • Number of events 1 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
0.00%
0/3 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
General disorders
Influenza like illness
0.00%
0/4 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
33.3%
1/3 • Number of events 1 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
General disorders
Non-cardiac chest pain
25.0%
1/4 • Number of events 1 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
0.00%
0/3 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
General disorders
Pain
25.0%
1/4 • Number of events 1 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
0.00%
0/3 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
Hepatobiliary disorders
Hepatic function abnormal
0.00%
0/4 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
33.3%
1/3 • Number of events 1 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
Immune system disorders
Seasonal allergy
25.0%
1/4 • Number of events 1 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
0.00%
0/3 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
Infections and infestations
Cystitis
0.00%
0/4 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
33.3%
1/3 • Number of events 1 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
Infections and infestations
Gastroenteritis
25.0%
1/4 • Number of events 1 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
0.00%
0/3 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
Infections and infestations
Respiratory tract infection viral
25.0%
1/4 • Number of events 1 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
0.00%
0/3 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
Infections and infestations
Upper respiratory tract infection
0.00%
0/4 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
33.3%
1/3 • Number of events 1 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
Injury, poisoning and procedural complications
Excoriation
25.0%
1/4 • Number of events 1 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
0.00%
0/3 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
Injury, poisoning and procedural complications
Skeletal injury
0.00%
0/4 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
33.3%
1/3 • Number of events 1 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
Investigations
Blood bilirubin increased
0.00%
0/4 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
33.3%
1/3 • Number of events 1 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
Metabolism and nutrition disorders
Hyperkalaemia
0.00%
0/4 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
33.3%
1/3 • Number of events 2 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
Musculoskeletal and connective tissue disorders
Myalgia
25.0%
1/4 • Number of events 1 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
0.00%
0/3 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
Nervous system disorders
Headache
25.0%
1/4 • Number of events 1 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
0.00%
0/3 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
Nervous system disorders
Presyncope
25.0%
1/4 • Number of events 1 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
33.3%
1/3 • Number of events 1 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
Nervous system disorders
Tension headache
50.0%
2/4 • Number of events 4 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
0.00%
0/3 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
Renal and urinary disorders
Proteinuria
0.00%
0/4 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
66.7%
2/3 • Number of events 3 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
Respiratory, thoracic and mediastinal disorders
Hyperventilation
0.00%
0/4 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
33.3%
1/3 • Number of events 1 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
Respiratory, thoracic and mediastinal disorders
Hypopnoea
0.00%
0/4 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
33.3%
1/3 • Number of events 1 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
Respiratory, thoracic and mediastinal disorders
Nasal discomfort
0.00%
0/4 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
33.3%
1/3 • Number of events 1 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
Respiratory, thoracic and mediastinal disorders
Nasal ulcer
0.00%
0/4 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
33.3%
1/3 • Number of events 1 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
Respiratory, thoracic and mediastinal disorders
Tachypnoea
75.0%
3/4 • Number of events 4 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
100.0%
3/3 • Number of events 6 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
Respiratory, thoracic and mediastinal disorders
Throat irritation
25.0%
1/4 • Number of events 1 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
0.00%
0/3 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
Skin and subcutaneous tissue disorders
Rash follicular
25.0%
1/4 • Number of events 1 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
33.3%
1/3 • Number of events 1 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
Vascular disorders
Phlebitis
25.0%
1/4 • Number of events 1 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.
0.00%
0/3 • From Day -2 to Day 360
Safety population included all participants who received any amount of investigational product.

Additional Information

Hasan Jafri, Medical Director

Medimmune, LLC

Phone: 301-398-4431

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 ongoing 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