AZD7442 Pharmacokinetics, Pharmacodynamics, and Safety Evaluation in Pediatrics (TRUST)

Open-Label, Uncontrolled, Single Dose Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Safety of AZD7442 in Pediatric Participants Aged ≥ 29 Weeks Gestational Age to < 18 Years

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.

Study Overview

• Status: Active, not recruiting
• Conditions: SARS-CoV-2
• Intervention / Treatment: Drug: AZD7442

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.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Research Site
• Brazil
  • Belo Horizonte, Brazil, 30130-100
    • Research Site
  • Porto Alegre, Brazil, 90035-001
    • Research Site
• Germany
  • Frankfurt am Main, Germany, 60590
    • Research Site
• United Kingdom
  • Southampton, United Kingdom, SO16 6YD
    • Research Site
• United States
  • California
    • Long Beach, California, United States, 90806
      • Research Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Research Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Research Site
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Research Site
  • New York
    • Stony Brook, New York, United States, 11794
      • Research Site
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Research Site
  • South Carolina
    • Mount Pleasant, South Carolina, United States, 29464
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AZD7442; 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; 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.; Other Names: Evusheld

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum concentrations of AZD7442	The serum concentrations of AZD7442 after a single IM or IV dose in pediatric participants will be evaluated.	Day 1 to Day 366
Maximum serum concentration (Cmax)	The Cmax of AZD7442 after a single dose in pediatric participants will be evaluated.	Day 1 to Day 366
Time to reach maximum serum concentration (tmax)	The tmax of AZD7442 after a single dose in pediatric participants will be evaluated.	Day 1 to Day 366
Terminal half-life (t1/2)	The t1/2 of AZD7442 after a single dose in pediatric participants will be evaluated.	Day 1 to Day 366
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 dose in pediatric participants will be evaluated.	Day 1 to Day 366
Area under the serum concentration versus time curve extrapolated to infinity (AUC0-inf)	The AUC0-inf of AZD7442 after a single dose in pediatric participants will be evaluated.	Day 1 to Day 366
Time to last measurable concentration (tlast)	The tlast of AZD7442 after a single dose in pediatric participants will be evaluated.	Day 1 to Day 366
Percentage of AUC0-inf extrapolated to infinity (% AUCex)	The %AUCex of AZD7442 after a single dose in pediatric participants will be evaluated.	Day 1 to Day 366
Apparent total clearance (CL/F)	The CL/F of AZD7442 after a single dose in pediatric participants will be evaluated.	Day 1 to Day 366
Apparent volume of distribution based on terminal phase (Vz/F)	The Vz/F of AZD7442 after a single dose in pediatric participants will be evaluated.	Day 1 to Day 366
Systemic clearance (CL)	The CL of AZD7442 after a single dose in pediatric participants will be evaluated.	Day 1 to Day 366
Volume of distribution at steady state (Vss)	The Vss of AZD7442 after a single dose in pediatric participants will be evaluated.	Day 1 to Day 366
Model-derived predicted serum AZD7442 concentrations	The serum concentrations of AZD7442 after a single dose in pediatric participants will be model-derived.	Day 1 to Day 366
Model-derived predicted AUC0-inf	The AUC0-inf of AZD7442 after a single dose in pediatric participants will be model-derived.	Day 1 to Day 366
Number of participants with adverse events (Treatment Emergent Adverse Events [TEAEs], Serious Adverse Events [SAEs], and Adverse Event of Special Interests [AESIs])	The safety and tolerability of AZD7442 after a single dose in pediatric participants will be evaluated.	Day 1 to Day 457 (upto 15 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All Cohorts (Other than Neonates) Titer of SARS-CoV-2 neutralizing antibodies (nAb)	The PD of AZD7442 after a single dose in pediatric participants will be evaluated.	Day 1 to Day 366
All Cohorts (Other than Neonates) - Number of participants with positive/negative antidrug antibodies (ADA) result and nAb to AZD7442.	The immunogenicity profile of AZD7442 after a single dose in pediatric participants will be evaluated. Number of participants with positive/negative ADA result and nAb to AZD7442 will be evaluated.	Day 1 to Day 366
Cohort 1 (Prophylaxis) - Incidence of SARS-CoV-2 infections	The incidence of SARS-CoV-2 infections with or without COVID-19 symptoms after a single dose of AZD7442 in pediatric participants will be evaluated.	Day 1 to Day 366
Cohort 2 and Cohort 3 (Treatment) - Change from baseline to Day 8 in viral load	The SARS-CoV-2 viral loads measured by qRT-PCR after a single dose of AZD7442 in pediatric participants will be evaluated.	Baseline, Day 8
Cohort 2 and Cohort 3 (Treatment) - Proportion of participants with progression of COVID-19	The percentage of participants with progression of COVID-19 after a single dose of AZD7442 in pediatric participants will be evaluated.	Day 1 to Day 29
Cohort 2 and Cohort 3 (Treatment) - The incidence of COVID-19-related death occurring after dosing with IMP through 90 days	COVID-19-related death after a single dose of AZD7442 in pediatric participants will be evaluated.	Day 1 to Day 90
Cohort 3 (Severe COVID-19) - Time to sustained recovery	The time to sustained recovery from severe COVID-19 after a single dose of AZD7442 in pediatric participants will be evaluated.	Day 1 to Day 366 (from the index hospitalization followed by being alive and home for 14 consecutive days)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nasal concentrations of AZD7442 at specified time points during the study period when administered as a single IM or IV dose	The concentration of AZD7442 in nasal fluid after a single dose in pediatric participants will be evaluated.	Post Day 1 to Day 366

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2022
• Primary Completion (Estimated): March 29, 2024
• Study Completion (Estimated): March 29, 2024

Study Registration Dates

• First Submitted: February 16, 2022
• First Submitted That Met QC Criteria: March 11, 2022
• First Posted (Actual): March 16, 2022

Study Record Updates

• Last Update Posted (Actual): December 22, 2023
• Last Update Submitted That Met QC Criteria: December 21, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: COVID-19; EVUSHELD; AZD7442; Monoclonal antibodies (mAb)
• Additional Relevant MeSH Terms: Anti-Infective Agents; Antiviral Agents; Cilgavimab and tixagevimab drug combination
• Other Study ID Numbers: D8850C00006; 2021-006056-13 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing 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.
• IPD Sharing 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No