Evaluate PK Profile
Conditions
Keywords
PK, safety, tolerability, Nirsevimab, healthy Chinese Adults, Respiratory Syncytial Viral (RSV)
Brief summary
The purpose of this study is to evaluate the Pharmacokinetics, Safety, Tolerability of Nirsevimab in Healthy Chinese Adults.
Detailed description
This is a Phase 1, randomized, double-blind, placebo-controlled study to evaluate the PK, safety and tolerability, and ADA of nirsevimab when administered as a single fixed IM dosage to healthy Chinese adult subjects. Enrolment is planned at a single study center in China. Approximately 24 subjects will be randomly assigned in a 3:1 ratio to receive nirsevimab (n = 18) or placebo (n = 6). All subjects will be followed for approximately 150 days after dosing to assess safety, PK, and ADA response.
Interventions
BIOLOGICALnirsevimab
Drug: injection, a single fixed IM dose on day 1 only.
OTHERPlacebo
Placebo: injection, 0.9% (w/v) saline, a single fixed IM dose on day 1 only.
Sponsors
IQVIA RDS (Shanghai) Co., Ltd.
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Age 18 to 45 years 2. Weight ≥ 45 kg and ≤ 110 kg and Body Mass Index of 19 to 26 kg/m2 3. Healthy Chinese subjects (both male and female) 4. Normotensive 5. Normal electrocardiogram (ECG) within 28 days prior to Day 1
Exclusion criteria
1. Acute illness at study entry (pre-dose on Day 1) 2. Fever ≥99.5°F (37.5°C) on day of dosing 3. Any drug therapy within 14 days prior to Day 1 (except contraceptives). 4. Receipt of immunoglobulin or blood products within 6 months prior to study entry. 5. Receipt of any investigational drug therapy within 120 days prior to investigational product dosing or planned to receive any investigational drug therapy within 150 days after investigational product dosing. 6. Previous receipt of any marketed or investigational mAb. 7. Previous vaccination against RSV. 8. History of immunodeficiency or receipt of immunosuppressive medications during the prior year. 9. History of asthma. 10. History of autoimmune disorder. 11. Evidence of any systemic disease on physical examination. 12. Evidence of infection with hepatitis A, B, or C virus, syphilis, or human immunodeficiency virus. 13. Any clinically significant abnormal laboratory assessments at screening. 14. Pregnant or nursing mother. 15. Alcohol or drug abuse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum Concentrations of Nirsevimab | Pre-dose on Day 1 and on Days 2, 4, 6, 8, 15, 31, 91, 151 post-dose. | Serum samples were collected at indicated timepoints to determine the serum concentration of nirsevimab. |
| Maximum Observed Serum Concentration (Cmax) for Nirsevimab | Pre-dose on Day 1 and on Days 2, 4, 6, 8, 15, 31, 91, 151 post-dose | Cmax for nirsevimab was directly calculated from the individual concentration-time curve. |
| Time to Reach Maximum Observed Serum Concentration (Tmax) for Nirsevimab | Pre-dose on Day 1 and on Days 2, 4, 6, 8, 15, 31, 91, 151 post-dose | Tmax for nirsevimab was directly calculated from the individual concentration-time curve. |
| Area Under the Serum Concentration-Time Curve From Time 0 to 150 Days (AUC0-150) for Nirsevimab | Pre-dose on Day 1 and on Days 2, 4, 6, 8, 15, 31, 91, 151 post-dose | Area Under the Serum Concentration-Time Curve From Time 0 to 150 Days (AUC0-150) for Nirsevimab was calculated by linear up/log down trapezoidal summation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Positive Anti-Drug Antibody (ADA) of Nirsevimab | Baseline (Day 1) and Days 31, 91 and 151 | ADA positive was defined as any participant with a positive ADA result available at any time, including baseline and all post-baseline measurements; otherwise ADA negative. |
Countries
China
Participant flow
Recruitment details
This was a Phase 1, placebo-controlled, study to evaluate pharmacokinetics (PK), safety, and tolerability of nirsevimab compared to placebo in healthy participants conducted at a single center in China.
Pre-assignment details
This study consisted of a screening period (28 days) and treatment period (151 days). A total of 24 participants were randomized in a 3:1 ratio to receive either nirsevimab or placebo.
Participants by arm
| Arm | Count |
|---|---|
| Nirsevimab Participants received single fixed IM dose of nirsevimab on Day 1. | 18 |
| Placebo Participants received single fixed IM dose of placebo matching with nirsevimab on Day 1. | 6 |
| Total | 24 |
Baseline characteristics
| Characteristic | Nirsevimab | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 29.2 years STANDARD_DEVIATION 5.55 | 29.8 years STANDARD_DEVIATION 4.71 | 29.3 years STANDARD_DEVIATION 5.26 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants | 6 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 18 Participants | 6 Participants | 24 Participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Male | 15 Participants | 2 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 6 |
| other Total, other adverse events | 5 / 18 | 2 / 6 |
| serious Total, serious adverse events | 0 / 18 | 0 / 6 |
Outcome results
Primary
Area Under the Serum Concentration-Time Curve From Time 0 to 150 Days (AUC0-150) for Nirsevimab
Area Under the Serum Concentration-Time Curve From Time 0 to 150 Days (AUC0-150) for Nirsevimab was calculated by linear up/log down trapezoidal summation.
Time frame: Pre-dose on Day 1 and on Days 2, 4, 6, 8, 15, 31, 91, 151 post-dose
Population: The PK population included all participants who received any dose of study treatment and had at least one measurable post-dose serum PK observation and for whom PK blood samples were assumed not to be affected by factors such as important protocol deviations (if any, determined prior to unblinding).~Only participants who received nirsevimab were analyzed for PK outcome measures.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Nirsevimab | Area Under the Serum Concentration-Time Curve From Time 0 to 150 Days (AUC0-150) for Nirsevimab | 4210.56 mcg*day/mL | Geometric Coefficient of Variation 13.6 |
Primary
Maximum Observed Serum Concentration (Cmax) for Nirsevimab
Cmax for nirsevimab was directly calculated from the individual concentration-time curve.
Time frame: Pre-dose on Day 1 and on Days 2, 4, 6, 8, 15, 31, 91, 151 post-dose
Population: The PK population included all participants who received any dose of study treatment and had at least one measurable post-dose serum PK observation and for whom PK blood samples were assumed not to be affected by factors such as important protocol deviations (if any, determined prior to unblinding).~Only participants who received nirsevimab were analyzed for PK outcome measures.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Nirsevimab | Maximum Observed Serum Concentration (Cmax) for Nirsevimab | 46.882 mcg/mL | Geometric Coefficient of Variation 21.7 |
Primary
Serum Concentrations of Nirsevimab
Serum samples were collected at indicated timepoints to determine the serum concentration of nirsevimab.
Time frame: Pre-dose on Day 1 and on Days 2, 4, 6, 8, 15, 31, 91, 151 post-dose.
Population: The PK population included all participants who received any dose of study treatment and had at least one measurable post-dose serum PK observation and for whom PK blood samples were assumed not to be affected by factors such as important protocol deviations (if any, determined prior to unblinding).~Only participants who received nirsevimab were analyzed for PK outcome measures.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nirsevimab | Serum Concentrations of Nirsevimab | Pre-dose Day 1 | NA micrograms/milliliter (mcg/mL) | — |
| Nirsevimab | Serum Concentrations of Nirsevimab | Day 2 | 27.644 micrograms/milliliter (mcg/mL) | Standard Deviation 5.819 |
| Nirsevimab | Serum Concentrations of Nirsevimab | Day 4 | 41.794 micrograms/milliliter (mcg/mL) | Standard Deviation 8.447 |
| Nirsevimab | Serum Concentrations of Nirsevimab | Day 6 | 43.811 micrograms/milliliter (mcg/mL) | Standard Deviation 8.291 |
| Nirsevimab | Serum Concentrations of Nirsevimab | Day 8 | 46.050 micrograms/milliliter (mcg/mL) | Standard Deviation 12.484 |
| Nirsevimab | Serum Concentrations of Nirsevimab | Day 15 | 43.739 micrograms/milliliter (mcg/mL) | Standard Deviation 7.236 |
| Nirsevimab | Serum Concentrations of Nirsevimab | Day 31 | 40.300 micrograms/milliliter (mcg/mL) | Standard Deviation 5.391 |
| Nirsevimab | Serum Concentrations of Nirsevimab | Day 91 | 25.200 micrograms/milliliter (mcg/mL) | Standard Deviation 3.694 |
| Nirsevimab | Serum Concentrations of Nirsevimab | Day 151 | 17.597 micrograms/milliliter (mcg/mL) | Standard Deviation 3.854 |
Primary
Time to Reach Maximum Observed Serum Concentration (Tmax) for Nirsevimab
Tmax for nirsevimab was directly calculated from the individual concentration-time curve.
Time frame: Pre-dose on Day 1 and on Days 2, 4, 6, 8, 15, 31, 91, 151 post-dose
Population: The PK population included all participants who received any dose of study treatment and had at least one measurable post-dose serum PK observation and for whom PK blood samples were assumed not to be affected by factors such as important protocol deviations (if any, determined prior to unblinding).~Only participants who received nirsevimab were analyzed for PK outcome measures.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nirsevimab | Time to Reach Maximum Observed Serum Concentration (Tmax) for Nirsevimab | 6.99 days |
Secondary
Number of Participants With Positive Anti-Drug Antibody (ADA) of Nirsevimab
ADA positive was defined as any participant with a positive ADA result available at any time, including baseline and all post-baseline measurements; otherwise ADA negative.
Time frame: Baseline (Day 1) and Days 31, 91 and 151
Population: As-treated population included all participants who were randomized into the study and received any amount of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nirsevimab | Number of Participants With Positive Anti-Drug Antibody (ADA) of Nirsevimab | Baseline (Day 1) | 0 Participants |
| Nirsevimab | Number of Participants With Positive Anti-Drug Antibody (ADA) of Nirsevimab | Day 31 | 0 Participants |
| Nirsevimab | Number of Participants With Positive Anti-Drug Antibody (ADA) of Nirsevimab | Day 91 | 0 Participants |
| Nirsevimab | Number of Participants With Positive Anti-Drug Antibody (ADA) of Nirsevimab | Day 151 | 0 Participants |