SARS-CoV-2
Conditions
Keywords
AZD7442, Monoclonal antibodies (mAb), COVID-19, EVUSHELD
Brief summary
This study will evaluate the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of AZD7442 administered intramuscularly (IM) or intravenously (IV) in pediatric participants aged ≥ 29 weeks GA to \< 18 years.
Detailed description
This is a Phase I, open-label, uncontrolled, multi-country, multi-center, single-dose study. Initially, 2 cohorts of participants will be enrolled: 1) participants who are severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) negative at screening and have not knowingly been exposed to a SARS-CoV-2 positive individual (pre-exposure prophylaxis); and 2) participants who are SARS-CoV-2 RT-PCR positive at screening and have mild to moderate COVID-19 symptoms. A third cohort might be added for the treatment of severe COVID-19. If included, this third cohort will include participants who are SARS-CoV-2 positive at screening and have severe COVID-19.
Interventions
DRUGAZD7442
IM Administration: AZD8895 and AZD1061 (comprising AZD7442), must both be administered separately to the participant in a sequential order. IV Administration: AZD7442 is dosed by co-administration of AZD8895 and AZD1061 in a single IV infusion.
Sponsors
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
0 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Participant must be aged ≥ 29 weeks gestational age (GA) to \< 18 years of age. * Participant must weigh a minimum of 1.5 kg. COHORT 1 * Increased risk of severe COVID-19 because of immunocompromised state or one or more comorbid conditions that increase the risk of severe COVID-19. * Increased risk for SARS-CoV-2 infection. * Medically stable (disease not requiring significant change in therapy or hospitalization for worsening disease during the one month prior to enrollment). * A negative RT-PCR test collected ≤ 3 days prior to Day 1 or a negative rapid SARS-CoV-2 antigen test at screening. * No COVID-19 symptoms prior to enrollment within 10 days of dosing. * Increased risk for SARS-CoV-2 infection. COHORT 2 * Increased risk of severe COVID-19 because of immunocompromised state or one or more comorbid conditions that increase the risk of severe COVID-19. * Medically stable (disease not requiring significant change in therapy or hospitalization for worsening disease during the one month prior to enrollment). * A positive RT-PCR test collected ≤ 3 days prior to Day 1 or a positive rapid SARS-CoV-2 antigen test at screening. * Symptomatic participants must be dosed with IMP no more than 7 days from the self-reported date of first reported sign/symptom. * Oxygenation saturation of ≥ 92% obtained at rest within 24 hours prior to Day 1 unless the potential participant regularly receives chronic supplementary oxygen for an underlying lung condition. Note that Cohort 2 will only be included if the indication is progressed in adults. COHORT 3 * Participants hospitalized with COVID-19 with a time between onset of symptoms and dosing AZD7442 of ≤ 7 days. * A positive RT-PCR test collected ≤ 3 days before Day 1 or a positive rapid SARS-CoV-2 antigen test at screening. * Spontaneous blood Alanine Aminotransferase (ALT)/Aspartate Transaminase (AST) levels ≤ 5 times the ULN. * Glomerular Filtration Rate (GFR) ≥ 30 mL/min/1.73 m2. Participants will receive IM AZD7442 unless they meet any of the following criteria for IV administration: * The participant has severe COVID-19. * Contraindication of intramuscular (IM) dose due to thrombocytopenia, coagulation defects or any other condition that would compromise the absorption of AZD7442 or safety of the participant. * Physician considers IV the appropriate route.
Exclusion criteria
All Cohorts * Cohort 1: Significant infection or other acute illnesses including fever on or the day prior to receiving AZD7442. * History of SARS-CoV-1 or Middle East Respiratory Syndrome Coronavirus (MERS-CoV). * Cohorts 1 and 2: Current need for immediate medical attention or current need for hospitalization. * Mechanical ventilation or extracorporeal membrane oxygenation requirement for COVID-19. * History of allergic or reaction to any component of the study drug formulation. * History of hypersensitivity, injection/infusion-relation reactions or severe adverse reactions following administration of a monoclonal antibody (mAb). * Co-morbidity requiring surgery within 7 days prior to study entry or is deemed life-threatening within 30 days prior to study entry. * Prior receipt of convalescent COVID-19 plasma/sera or hyperimmune globulin therapy. * Prior receipt of mAb/biologic indicated for the prevention of SARS-CoV-2, treatment of COVID-19, or expected receipt during the period of study follow-up. * Prior receipt of a COVID-19 vaccine ≤ 14 days before screening or plan to receive a COVID-19 vaccination ≤ 14 days after IMP administration at study Visit 1. * History of alcohol or drug abuse within the past 2 years. * Investigational Drugs or Devices: Treatment with investigational drug or device in another clinical trial within the last 30 days or 5 half-lives of the drug (whichever is longer) prior to screening. Note: Participation in observational studies (ie, studies that do not require medication, blood draws, or an additional intervention) is not exclusionary. Interventional trials which do not include investigational drugs (only include approved therapies), or investigational treatment regimens may be considered if the blood draw requirements and study interventions are minimal and not deemed by the Investigator to interfere with completion of the planned study sampling and follow-up. * Vulnerable persons (eg, ward of the state, kept in detention).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Event of Special Interest (AESI) | Day 1 to day 366 or early discontinuation visit (approx. 24 months) | Number of pediatric participants with AESI after a single IM or IV dose were evaluated. An AESI is a pre-specified medically significant event that has the potential to be causally associated with a vaccine product. |
| Apparent Total Clearance (CL/F) | Day 1 to Day 366 or early discontinuation visit (approx. 24 months) | The CL/F of AZD7442 after a single IM dose in pediatric participants was evaluated. The PK parameters were summarized by route of administration using appropriate descriptive statistics based on the PK analysis set. |
| Apparent Volume of Distribution Based on Terminal Phase (Vz/F) | Day 1 to Day 366 or early discontinuation visit (approx. 24 months) | The Vz/F of AZD7442 after a single IM dose in pediatric participants was evaluated. The PK parameters were summarized by route of administration using appropriate descriptive statistics based on the PK analysis set. |
| Systemic Clearance (CL) | Day 1 to Day 366 or early discontinuation visit (approx. 24 months) | The CL of AZD7442 after a single IV dose in pediatric participants was evaluated. The PK parameters were summarized by route of administration using appropriate descriptive statistics based on the PK analysis set. |
| Volume of Distribution at Steady State (Vss) | Day 1 to Day 366 or early discontinuation visit (approx. 24 months) | The Vss of AZD7442 after a single IV dose in pediatric participants was evaluated. The PK parameters were summarized by route of administration using appropriate descriptive statistics based on the PK analysis set. |
| Number of Participants With Adverse Events (AE) | Day 1 to Day 366 or early discontinuation visit (approx. 24 months) | The safety and tolerability of AZD7442 after a single IM or IV dose in pediatric participants was evaluated. |
| Serum Concentrations of AZD7442 | IM - Day 4, Day 8, Day 11, Day 15 and Day 366; IV - Day 1, Day 4, Day 8, Day 11, Day 15 and Day 366 | The serum concentrations of AZD7442 after a single IM or IV dose in pediatric participants were evaluated. The serum concentrations for each scheduled time point were summarized by route of administration using appropriate descriptive statistics, based on the (Pharmacokinetic analysis) PK analysis set. |
| Maximum Serum Concentration (Cmax) | Day 1 to Day 366 or early discontinuation visit (approximately [approx.] 24 months) | The Cmax of AZD7442 after a single IM or IV dose in pediatric participants was evaluated. The PK parameters were summarized by route of administration using appropriate descriptive statistics based on the PK analysis set. |
| Time to Reach Maximum Serum Concentration (Tmax) | Day 1 to Day 366 or early discontinuation visit (approx. 24 months) | The tmax of AZD7442 after a single IM or IV dose in pediatric participants was evaluated. The PK parameters were summarized by route of administration using appropriate descriptive statistics based on the PK analysis set. |
| Terminal Half-life (t1/2) | Day 1 to Day 366 or early discontinuation visit (approx. 24 months) | The t1/2 of AZD7442 after a single IM or IV dose in pediatric participants was evaluated. The PK parameters were summarized by route of administration using appropriate descriptive statistics based on the PK analysis set. |
| Area Under the Serum Concentration Versus Time Curve From Time Zero to Time of Last Measurable Concentration (AUC0-last) | Day 1 to Day 366 or early discontinuation visit (approx. 24 months) | The AUC0-last of AZD7442 after a single IM or IV dose in pediatric participants was evaluated. The PK parameters were summarized by route of administration using appropriate descriptive statistics based on the PK analysis set. |
| Area Under the Serum Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf) | Day 1 to Day 366 or early discontinuation visit (approx. 24 months) | The AUC0-inf of AZD7442 after a single IM or IV dose in pediatric participants was evaluated. The PK parameters were summarized by route of administration using appropriate descriptive statistics based on the PK analysis set. |
| Time to Last Measurable Concentration (Tlast) | Day 1 to Day 366 or early discontinuation visit (approx. 24 months) | The tlast of AZD7442 after a single IM or IV dose in pediatric participants was evaluated. The PK parameters were summarized by route of administration using appropriate descriptive statistics based on the PK analysis set. |
| Percentage of AUC0-inf Extrapolated to Infinity (% AUCex) | Day 1 to Day 366 or early discontinuation visit (approx. 24 months) | The %AUCex of AZD7442 after a single IM or IV dose in pediatric participants was evaluated. The PK parameters were summarized by route of administration using appropriate descriptive statistics based on the PK analysis set. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cohort 2 - Percentage of Participants With Progression of COVID-19 Through Day 29 | Day 1 to Day 366 or early discontinuation visit (approx. 24 months) | Percentage of participants with progression of COVID-19 through Day 29 in Cohort 2 in pediatric participants was evaluated. |
| Cohort 2 - Number of Participants With COVID-19 Related Death Occurring After Dosing With IMP Through 90 Days | Day 1 to Day 366 or early discontinuation visit (approx. 24 months) | Number of participants with COVID-19 related death occurring after dosing with IMP through 90 days in Cohort 2 in pediatric participants were evaluated. |
| Titre of SARS-CoV-2 Neutralizing Antibodies | Day 31 to Day 366 or early discontinuation visit (approx. 24 months) | The pharmacodynamics of AZD7442 after a single dose in pediatric participants was evaluated. The result for overall vaccination status were presented. |
| Cohort 1 (Prophylaxis) - Number of Participants With SARS-CoV-2 Infections | Day 1 to Day 366 or early discontinuation visit (approx. 24 months) | Number of participants with SARS-CoV-2 infections with or without COVID-19 symptoms after a single IM or IV dose of AZD7442 in pediatric participants were evaluated. |
| Number of Participants With Positive Antidrug Antibodies (ADA) Result to AZD7442. | Day 1 to Day 366 or early discontinuation visit (approx. 24 months) | The immunogenicity profile of AZD7442 after a single IM or IV dose in pediatric participants was evaluated. A participant is defined as ADA-positive to AZD7442 if they have a positive ADA result to AZD8895 and/or AZD1061 at any time, including baseline and all postbaseline. |
Countries
Belgium, Brazil, Germany, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted from 21 March 2022 to 16 April 2024 at 11 sites in 5 countries worldwide.
Pre-assignment details
Participants who met the inclusion criteria and none of the exclusion criteria were enrolled to the study. All study assessments were performed as per the schedule of assessment.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Participants who were SARS-CoV-2 RT-PCR negative received single dose of AZD7442 on Day 1, either as IM (AZD8895 followed by AZD1061) or as IV (AZD8895 + AZD1061 concurrently) | 44 |
| Cohort 2 Participants who were SARS-CoV-2 RT-PCR positive received single dose of AZD7442 on Day 1, either as IM (AZD8895 followed by AZD1061) or as IV (AZD8895 + AZD1061 concurrently). | 2 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Physician Decision | 2 | 0 |
| Overall Study | Withdrawal by parent/guardian | 2 | 1 |
Baseline characteristics
| Characteristic | Cohort 1 | Cohort 2 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 44 Participants | 2 Participants | 46 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Black or African American | 11 Participants | 0 Participants | 11 Participants |
| Race/Ethnicity, Customized Race Multiple | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Not Reported | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Race Other | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Race White | 28 Participants | 0 Participants | 28 Participants |
| Sex: Female, Male Female | 25 Participants | 0 Participants | 25 Participants |
| Sex: Female, Male Male | 19 Participants | 2 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 44 | 0 / 2 |
| other Total, other adverse events | 34 / 44 | 2 / 2 |
| serious Total, serious adverse events | 8 / 44 | 1 / 2 |
Outcome results
Primary
Apparent Total Clearance (CL/F)
The CL/F of AZD7442 after a single IM dose in pediatric participants was evaluated. The PK parameters were summarized by route of administration using appropriate descriptive statistics based on the PK analysis set.
Time frame: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
Population: The PK analysis set consisted of all participants who received AZD7442 and from whom PK blood samples were assumed not to be affected by factors such as protocol violations, and who had at least one quantifiable serum PK observation post-dose.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Apparent Total Clearance (CL/F) | 0.04807 Liter/day | Geometric Coefficient of Variation 75.26 |
Primary
Apparent Volume of Distribution Based on Terminal Phase (Vz/F)
The Vz/F of AZD7442 after a single IM dose in pediatric participants was evaluated. The PK parameters were summarized by route of administration using appropriate descriptive statistics based on the PK analysis set.
Time frame: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
Population: The PK analysis set consisted of all participants who received AZD7442 and from whom PK blood samples were assumed not to be affected by factors such as protocol violations, and who had at least one quantifiable serum PK observation post-dose.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Apparent Volume of Distribution Based on Terminal Phase (Vz/F) | 5.475 Liter | Geometric Coefficient of Variation 98.74 |
Primary
Area Under the Serum Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf)
The AUC0-inf of AZD7442 after a single IM or IV dose in pediatric participants was evaluated. The PK parameters were summarized by route of administration using appropriate descriptive statistics based on the PK analysis set.
Time frame: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
Population: The PK analysis set consisted of all participants who received AZD7442 and from whom PK blood samples were assumed not to be affected by factors such as protocol violations, and who had at least one quantifiable serum PK observation post-dose.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Area Under the Serum Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf) | AZD7442 intramuscular | 11000 Day*ug/mL | Geometric Coefficient of Variation 38.03 |
| Cohort 1 | Area Under the Serum Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf) | AZD7442 intravenous | 10870 Day*ug/mL | Geometric Coefficient of Variation 21.09 |
| Cohort 2 | Area Under the Serum Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf) | AZD7442 intravenous | NA Day*ug/mL | — |
Primary
Area Under the Serum Concentration Versus Time Curve From Time Zero to Time of Last Measurable Concentration (AUC0-last)
The AUC0-last of AZD7442 after a single IM or IV dose in pediatric participants was evaluated. The PK parameters were summarized by route of administration using appropriate descriptive statistics based on the PK analysis set.
Time frame: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
Population: The PK analysis set consisted of all participants who received AZD7442 and from whom PK blood samples were assumed not to be affected by factors such as protocol violations, and who had at least one quantifiable serum PK observation post-dose.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Area Under the Serum Concentration Versus Time Curve From Time Zero to Time of Last Measurable Concentration (AUC0-last) | AZD7442 intramuscular | 9884 Day*ug/mL | Geometric Coefficient of Variation 42.84 |
| Cohort 1 | Area Under the Serum Concentration Versus Time Curve From Time Zero to Time of Last Measurable Concentration (AUC0-last) | AZD7442 intravenous | 9342 Day*ug/mL | Geometric Coefficient of Variation 36.45 |
| Cohort 2 | Area Under the Serum Concentration Versus Time Curve From Time Zero to Time of Last Measurable Concentration (AUC0-last) | AZD7442 intravenous | NA Day*ug/mL | — |
Primary
Maximum Serum Concentration (Cmax)
The Cmax of AZD7442 after a single IM or IV dose in pediatric participants was evaluated. The PK parameters were summarized by route of administration using appropriate descriptive statistics based on the PK analysis set.
Time frame: Day 1 to Day 366 or early discontinuation visit (approximately [approx.] 24 months)
Population: The PK analysis set consisted of all participants who received AZD7442 and from whom PK blood samples were assumed not to be affected by factors such as protocol violations, and who had at least one quantifiable serum PK observation post-dose.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Maximum Serum Concentration (Cmax) | AZD7442 intramuscular | 92.47 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 44.22 |
| Cohort 1 | Maximum Serum Concentration (Cmax) | AZD7442 intravenous | 189.3 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 27.72 |
| Cohort 2 | Maximum Serum Concentration (Cmax) | AZD7442 intravenous | NA Microgram per milliliter (ug/mL) | — |
Primary
Number of Participants With Adverse Event of Special Interest (AESI)
Number of pediatric participants with AESI after a single IM or IV dose were evaluated. An AESI is a pre-specified medically significant event that has the potential to be causally associated with a vaccine product.
Time frame: Day 1 to day 366 or early discontinuation visit (approx. 24 months)
Population: The SAF consisted of all participants who had received IMP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 | Number of Participants With Adverse Event of Special Interest (AESI) | 1 Participants |
| Cohort 2 | Number of Participants With Adverse Event of Special Interest (AESI) | 0 Participants |
Primary
Number of Participants With Adverse Events (AE)
The safety and tolerability of AZD7442 after a single IM or IV dose in pediatric participants was evaluated.
Time frame: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
Population: The SAF consisted of all participants who had received IMP.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 | Number of Participants With Adverse Events (AE) | Any Serious Adverse Event (SAE) | 8 Participants |
| Cohort 1 | Number of Participants With Adverse Events (AE) | Any possibly related AE | 3 Participants |
| Cohort 1 | Number of Participants With Adverse Events (AE) | Any SAE with outcome death | 1 Participants |
| Cohort 1 | Number of Participants With Adverse Events (AE) | Any possibly related SAE | 0 Participants |
| Cohort 1 | Number of Participants With Adverse Events (AE) | Any Severe AE | 6 Participants |
| Cohort 1 | Number of Participants With Adverse Events (AE) | Any possibly related Severe AE | 0 Participants |
| Cohort 1 | Number of Participants With Adverse Events (AE) | Any AE leading to study discontinuation | 0 Participants |
| Cohort 1 | Number of Participants With Adverse Events (AE) | Any possibly related Adverse Event of Special interest (AESI) | 1 Participants |
| Cohort 1 | Number of Participants With Adverse Events (AE) | Any AE | 39 Participants |
| Cohort 2 | Number of Participants With Adverse Events (AE) | Any possibly related Adverse Event of Special interest (AESI) | 0 Participants |
| Cohort 2 | Number of Participants With Adverse Events (AE) | Any AE | 2 Participants |
| Cohort 2 | Number of Participants With Adverse Events (AE) | Any Serious Adverse Event (SAE) | 1 Participants |
| Cohort 2 | Number of Participants With Adverse Events (AE) | Any Severe AE | 0 Participants |
| Cohort 2 | Number of Participants With Adverse Events (AE) | Any SAE with outcome death | 0 Participants |
| Cohort 2 | Number of Participants With Adverse Events (AE) | Any AE leading to study discontinuation | 0 Participants |
| Cohort 2 | Number of Participants With Adverse Events (AE) | Any possibly related AE | 0 Participants |
| Cohort 2 | Number of Participants With Adverse Events (AE) | Any possibly related SAE | 0 Participants |
| Cohort 2 | Number of Participants With Adverse Events (AE) | Any possibly related Severe AE | 0 Participants |
Primary
Percentage of AUC0-inf Extrapolated to Infinity (% AUCex)
The %AUCex of AZD7442 after a single IM or IV dose in pediatric participants was evaluated. The PK parameters were summarized by route of administration using appropriate descriptive statistics based on the PK analysis set.
Time frame: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
Population: The PK analysis set consisted of all participants who received AZD7442 and from whom PK blood samples were assumed not to be affected by factors such as protocol violations, and who had at least one quantifiable serum PK observation post-dose.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Percentage of AUC0-inf Extrapolated to Infinity (% AUCex) | AZD7442 intramuscular | 4.799 Percentage of AUC extrapolated to ∞ | Geometric Coefficient of Variation 78.26 |
| Cohort 1 | Percentage of AUC0-inf Extrapolated to Infinity (% AUCex) | AZD7442 intravenous | 3.018 Percentage of AUC extrapolated to ∞ | Geometric Coefficient of Variation 179.9 |
| Cohort 2 | Percentage of AUC0-inf Extrapolated to Infinity (% AUCex) | AZD7442 intravenous | NA Percentage of AUC extrapolated to ∞ | — |
Primary
Serum Concentrations of AZD7442
The serum concentrations of AZD7442 after a single IM or IV dose in pediatric participants were evaluated. The serum concentrations for each scheduled time point were summarized by route of administration using appropriate descriptive statistics, based on the (Pharmacokinetic analysis) PK analysis set.
Time frame: IM - Day 4, Day 8, Day 11, Day 15 and Day 366; IV - Day 1, Day 4, Day 8, Day 11, Day 15 and Day 366
Population: The PK set consisted of all participants who received AZD7442 and from whom PK blood samples were assumed not to be affected by factors such as protocol violations, and who had at least one quantifiable serum PK observation post-dose.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Serum Concentrations of AZD7442 | Day 4 AZD7442 intramuscular | 86.32 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 72.72 |
| Cohort 1 | Serum Concentrations of AZD7442 | Day 8 AZD7442 intramuscular | 91.88 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 86.03 |
| Cohort 1 | Serum Concentrations of AZD7442 | Day 11 AZD7442 intramuscular | 92.49 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 20.91 |
| Cohort 1 | Serum Concentrations of AZD7442 | Day 15 AZD7442 intramuscular | 84.69 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 33.69 |
| Cohort 1 | Serum Concentrations of AZD7442 | Day 366 AZD7442 intramuscular | 4.084 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 57.91 |
| Cohort 1 | Serum Concentrations of AZD7442 | Day 1 AZD7442 intravenous | 199.9 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 23.16 |
| Cohort 1 | Serum Concentrations of AZD7442 | Day 11 AZD7442 intravenous | 95.02 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 20.35 |
| Cohort 1 | Serum Concentrations of AZD7442 | Day 15 AZD7442 intravenous | NA Microgram per milliliter (ug/mL) | — |
| Cohort 1 | Serum Concentrations of AZD7442 | Day 366 AZD7442 intravenous | 2.047 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 74.56 |
| Cohort 1 | Serum Concentrations of AZD7442 | Day 4 AZD7442 intravenous | NA Microgram per milliliter (ug/mL) | — |
| Cohort 1 | Serum Concentrations of AZD7442 | Day 8 AZD7442 intravenous | 89.47 Microgram per milliliter (ug/mL) | Geometric Coefficient of Variation 30.6 |
| Cohort 2 | Serum Concentrations of AZD7442 | Day 1 AZD7442 intravenous | NA Microgram per milliliter (ug/mL) | — |
| Cohort 2 | Serum Concentrations of AZD7442 | Day 15 AZD7442 intravenous | NA Microgram per milliliter (ug/mL) | — |
| Cohort 2 | Serum Concentrations of AZD7442 | Day 366 AZD7442 intravenous | NA Microgram per milliliter (ug/mL) | — |
Primary
Systemic Clearance (CL)
The CL of AZD7442 after a single IV dose in pediatric participants was evaluated. The PK parameters were summarized by route of administration using appropriate descriptive statistics based on the PK analysis set.
Time frame: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
Population: The PK analysis set consisted of all participants who received AZD7442 and from whom PK blood samples were assumed not to be affected by factors such as protocol violations, and who had at least one quantifiable serum PK observation post-dose.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Systemic Clearance (CL) | 0.02759 Liter/day | Geometric Coefficient of Variation 21.09 |
| Cohort 2 | Systemic Clearance (CL) | NA Liter/day | — |
Primary
Terminal Half-life (t1/2)
The t1/2 of AZD7442 after a single IM or IV dose in pediatric participants was evaluated. The PK parameters were summarized by route of administration using appropriate descriptive statistics based on the PK analysis set.
Time frame: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
Population: The PK analysis set consisted of all participants who received AZD7442 and from whom PK blood samples were assumed not to be affected by factors such as protocol violations, and who had at least one quantifiable serum PK observation post-dose.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 | Terminal Half-life (t1/2) | AZD7442 intramuscular | 78.95 Day | Geometric Coefficient of Variation 24.21 |
| Cohort 1 | Terminal Half-life (t1/2) | AZD7442 intravenous | 65.61 Day | Geometric Coefficient of Variation 22.38 |
| Cohort 2 | Terminal Half-life (t1/2) | AZD7442 intravenous | NA Day | — |
Primary
Time to Last Measurable Concentration (Tlast)
The tlast of AZD7442 after a single IM or IV dose in pediatric participants was evaluated. The PK parameters were summarized by route of administration using appropriate descriptive statistics based on the PK analysis set.
Time frame: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
Population: The PK analysis set consisted of all participants who received AZD7442 and from whom PK blood samples were assumed not to be affected by factors such as protocol violations, and who had at least one quantifiable serum PK observation post-dose.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1 | Time to Last Measurable Concentration (Tlast) | AZD7442 intramuscular | 351.38 Day |
| Cohort 1 | Time to Last Measurable Concentration (Tlast) | AZD7442 intravenous | 355.97 Day |
| Cohort 2 | Time to Last Measurable Concentration (Tlast) | AZD7442 intravenous | NA Day |
Primary
Time to Reach Maximum Serum Concentration (Tmax)
The tmax of AZD7442 after a single IM or IV dose in pediatric participants was evaluated. The PK parameters were summarized by route of administration using appropriate descriptive statistics based on the PK analysis set.
Time frame: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
Population: The PK analysis set consisted of all participants who received AZD7442 and from whom PK blood samples were assumed not to be affected by factors such as protocol violations, and who had at least one quantifiable serum PK observation post-dose.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1 | Time to Reach Maximum Serum Concentration (Tmax) | AZD7442 intramuscular | 11.44 Day |
| Cohort 1 | Time to Reach Maximum Serum Concentration (Tmax) | AZD7442 intravenous | 0.01 Day |
| Cohort 2 | Time to Reach Maximum Serum Concentration (Tmax) | AZD7442 intravenous | NA Day |
Primary
Volume of Distribution at Steady State (Vss)
The Vss of AZD7442 after a single IV dose in pediatric participants was evaluated. The PK parameters were summarized by route of administration using appropriate descriptive statistics based on the PK analysis set.
Time frame: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
Population: The PK analysis set consisted of all participants who received AZD7442 and from whom PK blood samples were assumed not to be affected by factors such as protocol violations, and who had at least one quantifiable serum PK observation post-dose.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Volume of Distribution at Steady State (Vss) | 2.605 Liter | Geometric Coefficient of Variation 20.34 |
| Cohort 2 | Volume of Distribution at Steady State (Vss) | NA Liter | — |
Secondary
Cohort 1 (Prophylaxis) - Number of Participants With SARS-CoV-2 Infections
Number of participants with SARS-CoV-2 infections with or without COVID-19 symptoms after a single IM or IV dose of AZD7442 in pediatric participants were evaluated.
Time frame: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
Population: The SAF consisted of all participants who had received IMP.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 | Cohort 1 (Prophylaxis) - Number of Participants With SARS-CoV-2 Infections | Overall | 10 Participants |
| Cohort 1 | Cohort 1 (Prophylaxis) - Number of Participants With SARS-CoV-2 Infections | Intramuscular administration | 7 Participants |
| Cohort 1 | Cohort 1 (Prophylaxis) - Number of Participants With SARS-CoV-2 Infections | Intravenous administration | 3 Participants |
Secondary
Cohort 2 - Number of Participants With COVID-19 Related Death Occurring After Dosing With IMP Through 90 Days
Number of participants with COVID-19 related death occurring after dosing with IMP through 90 days in Cohort 2 in pediatric participants were evaluated.
Time frame: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
Population: The SAF consisted of all participants who had received IMP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 | Cohort 2 - Number of Participants With COVID-19 Related Death Occurring After Dosing With IMP Through 90 Days | 0 Participants |
Secondary
Cohort 2 - Percentage of Participants With Progression of COVID-19 Through Day 29
Percentage of participants with progression of COVID-19 through Day 29 in Cohort 2 in pediatric participants was evaluated.
Time frame: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
Population: The SAF consisted of all participants who had received IMP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Cohort 2 - Percentage of Participants With Progression of COVID-19 Through Day 29 | 0 Percentage of participants |
Secondary
Number of Participants With Positive Antidrug Antibodies (ADA) Result to AZD7442.
The immunogenicity profile of AZD7442 after a single IM or IV dose in pediatric participants was evaluated. A participant is defined as ADA-positive to AZD7442 if they have a positive ADA result to AZD8895 and/or AZD1061 at any time, including baseline and all postbaseline.
Time frame: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
Population: The AZD7442 ADA Evaluable Analysis Set (ADS3) consisted of all participants who were AZD8895 ADA evaluable and/or AZD1061 ADA evaluable.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 | Number of Participants With Positive Antidrug Antibodies (ADA) Result to AZD7442. | AZD7442 intramuscular ADA positive subject | 2 Participants |
| Cohort 1 | Number of Participants With Positive Antidrug Antibodies (ADA) Result to AZD7442. | AZD7442 intravenous ADA positive subject | 2 Participants |
| Cohort 2 | Number of Participants With Positive Antidrug Antibodies (ADA) Result to AZD7442. | AZD7442 intramuscular ADA positive subject | 0 Participants |
| Cohort 2 | Number of Participants With Positive Antidrug Antibodies (ADA) Result to AZD7442. | AZD7442 intravenous ADA positive subject | 0 Participants |
Secondary
Titre of SARS-CoV-2 Neutralizing Antibodies
The pharmacodynamics of AZD7442 after a single dose in pediatric participants was evaluated. The result for overall vaccination status were presented.
Time frame: Day 31 to Day 366 or early discontinuation visit (approx. 24 months)
Population: The SARS-CoV-2 nAb Evaluable Analysis Set (SES) consisted of all participants in the Safety Analysis Set from whom blood samples were assumed not to be affected by factors such as protocol violations, and who had at least one quantifiable serum titer observation post dose.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort 1 | Titre of SARS-CoV-2 Neutralizing Antibodies | Intramuscular Day 31 | 52720 ug/mL |
| Cohort 1 | Titre of SARS-CoV-2 Neutralizing Antibodies | Intramuscular Day 366 | 1699 ug/mL |
| Cohort 1 | Titre of SARS-CoV-2 Neutralizing Antibodies | Intravenous Day 31 | 52950 ug/mL |
| Cohort 1 | Titre of SARS-CoV-2 Neutralizing Antibodies | Intravenous Day 366 | 1078 ug/mL |
| Cohort 2 | Titre of SARS-CoV-2 Neutralizing Antibodies | Intravenous Day 31 | NA ug/mL |
| Cohort 2 | Titre of SARS-CoV-2 Neutralizing Antibodies | Intravenous Day 366 | NA ug/mL |