AZD7442 Pharmacokinetics, Pharmacodynamics, and Safety Evaluation in Pediatrics

NCT05281601 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: D8850C000062021-006056-13
• Study Type: interventional
• Target: 46
• Locations: 5 countries
• Sites: 11

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.

Conditions

SARS-CoV-2

Keywords

AZD7442; Monoclonal antibodies (mAb); COVID-19; EVUSHELD

Outcome Measures

Primary Outcomes (14)

• 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.

  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

• 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.

  Day 1 to Day 366 or early discontinuation visit (approximately [approx.] 24 months)

• 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.

  Day 1 to Day 366 or early discontinuation visit (approx. 24 months)

• 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.

  Day 1 to Day 366 or early discontinuation visit (approx. 24 months)

• 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.

  Day 1 to Day 366 or early discontinuation visit (approx. 24 months)

• 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.

  Day 1 to Day 366 or early discontinuation visit (approx. 24 months)

• 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.

  Day 1 to Day 366 or early discontinuation visit (approx. 24 months)

• 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.

  Day 1 to Day 366 or early discontinuation visit (approx. 24 months)

• 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.

  Day 1 to Day 366 or early discontinuation visit (approx. 24 months)

• 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.

  Day 1 to Day 366 or early discontinuation visit (approx. 24 months)

• 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.

  Day 1 to Day 366 or early discontinuation visit (approx. 24 months)

• 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.

  Day 1 to Day 366 or early discontinuation visit (approx. 24 months)

• 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.

  Day 1 to Day 366 or early discontinuation visit (approx. 24 months)

• 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.

  Day 1 to day 366 or early discontinuation visit (approx. 24 months)

Secondary Outcomes (5)

• Number of Participants With Positive Antidrug Antibodies (ADA) Result to AZD7442.

  Day 1 to Day 366 or early discontinuation visit (approx. 24 months)

• 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)

• 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)

• Titre of SARS-CoV-2 Neutralizing Antibodies

  Day 31 to Day 366 or early discontinuation visit (approx. 24 months)

• Cohort 1 (Prophylaxis) - Number of Participants With SARS-CoV-2 Infections

  Day 1 to Day 366 or early discontinuation visit (approx. 24 months)

Study Arms (1)

AZD7442

EXPERIMENTAL

All participants will receive a single dose of AZD7442 on Day 1, either IM (AZD8895 followed by AZD1061) or IV (AZD8895 + AZD1061 concurrently).

Drug: AZD7442

Interventions

AZD7442 DRUG

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.

Also known as: Evusheld

AZD7442

Eligibility Criteria

• Age: 0 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• Vulnerable persons (eg, ward of the state, kept in detention).

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (11)

Research Site

Long Beach, California, 90806, United States

Location

Research Site

Aurora, Colorado, 80045, United States

Location

Research Site

Washington D.C., District of Columbia, 20007, United States

Location

Research Site

Idaho Falls, Idaho, 83404, United States

Location

Research Site

Stony Brook, New York, 11794, United States

Location

Research Site

Providence, Rhode Island, 02903, United States

Location

Research Site

Mt. Pleasant, South Carolina, 29464, United States

Location

Research Site

Leuven, 3000, Belgium

Location

Research Site

Belo Horizonte, 30130-100, Brazil

Location

Research Site

Frankfurt am Main, 60590, Germany

Location

Research Site

Southampton, SO16 6YD, United Kingdom

Location

Related Links

• D8850C00006\_Redacted\_CSP
• D8850C00006\_Redacted\_CSR\_Synopsi
• D8850C00006\_Redacted\_SAP.

MeSH Terms

Conditions

COVID-19

Interventions

cilgavimab and tixagevimab drug combination

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 16, 2022
• First Posted: March 16, 2022
• Study Start: March 21, 2022
• Primary Completion: April 16, 2024
• Study Completion: April 16, 2024
• Last Updated: April 18, 2025
• Results First Posted: April 18, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

DE (1); GB (1); US (7); BE (1); BR (1)