Clincosm LogoSign in Get a demo

TRUST: AZD7442 Pharmacokinetics, Pharmacodynamics, and Safety Evaluation in Pediatrics

Sponsor
AstraZeneca (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05281601
Collaborator
(none)
100
Enrollment
35
Locations
1
Arm
24
Anticipated Duration (Months)
2.9
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

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 Design

Study Type:
Interventional
Anticipated Enrollment :
100 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Mar 21, 2022
Anticipated Primary Completion Date :
Jul 28, 2022
Anticipated Study Completion Date :
Mar 19, 2024

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Serum concentrations of AZD7442 [Day 1 to Day 366]

      The serum concentrations of AZD7442 after a single IM or IV dose in pediatric participants will be evaluated.

    2. Maximum serum concentration (Cmax) [Day 1 to Day 366]

      The Cmax of AZD7442 after a single dose in pediatric participants will be evaluated.

    3. Time to reach maximum serum concentration (tmax) [Day 1 to Day 366]

      The tmax of AZD7442 after a single dose in pediatric participants will be evaluated.

    4. Terminal half-life (t1/2) [Day 1 to Day 366]

      The t1/2 of AZD7442 after a single dose in pediatric participants will be evaluated.

    5. Area under the serum concentration versus time curve from time zero to time of last measurable concentration (AUC0-last) [Day 1 to Day 366]

      The AUC0-last of AZD7442 after a single dose in pediatric participants will be evaluated.

    6. Area under the serum concentration versus time curve extrapolated to infinity (AUC0-inf) [Day 1 to Day 366]

      The AUC0-inf of AZD7442 after a single dose in pediatric participants will be evaluated.

    7. Time to last measurable concentration (tlast) [Day 1 to Day 366]

      The tlast of AZD7442 after a single dose in pediatric participants will be evaluated.

    8. Percentage of AUC0-inf extrapolated to infinity (% AUCex) [Day 1 to Day 366]

      The %AUCex of AZD7442 after a single dose in pediatric participants will be evaluated.

    9. Apparent total clearance (CL/F) [Day 1 to Day 366]

      The CL/F of AZD7442 after a single dose in pediatric participants will be evaluated.

    10. Apparent volume of distribution based on terminal phase (Vz/F) [Day 1 to Day 366]

      The Vz/F of AZD7442 after a single dose in pediatric participants will be evaluated.

    11. Systemic clearance (CL) [Day 1 to Day 366]

      The CL of AZD7442 after a single dose in pediatric participants will be evaluated.

    12. Volume of distribution at steady state (Vss) [Day 1 to Day 366]

      The Vss of AZD7442 after a single dose in pediatric participants will be evaluated.

    13. Model-derived predicted serum AZD7442 concentrations [Day 1 to Day 366]

      The serum concentrations of AZD7442 after a single dose in pediatric participants will be model-derived.

    14. Model-derived predicted AUC0-inf [Day 1 to Day 366]

      The AUC0-inf of AZD7442 after a single dose in pediatric participants will be model-derived.

    15. Number of participants with adverse events (Treatment Emergent Adverse Events [TEAEs], Serious Adverse Events [SAEs], and Adverse Event of Special Interests [AESIs]) [Day 1 to Day 457 (upto 15 months)]

      The safety and tolerability of AZD7442 after a single dose in pediatric participants will be evaluated.

    Secondary Outcome Measures

    1. All Cohorts (Other than Neonates) Titer of SARS-CoV-2 neutralizing antibodies (nAb) [Day 1 to Day 366]

      The PD of AZD7442 after a single dose in pediatric participants will be evaluated.

    2. All Cohorts (Other than Neonates) - Number of participants with positive/negative antidrug antibodies (ADA) result and nAb to AZD7442. [Day 1 to Day 366]

      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.

    3. Cohort 1 (Prophylaxis) - Incidence of SARS-CoV-2 infections [Day 1 to Day 366]

      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.

    4. Cohort 2 and Cohort 3 (Treatment) - Change from baseline to Day 8 in viral load [Baseline, Day 8]

      The SARS-CoV-2 viral loads measured by qRT-PCR after a single dose of AZD7442 in pediatric participants will be evaluated.

    5. Cohort 2 and Cohort 3 (Treatment) - Proportion of participants with progression of COVID-19 [Day 1 to Day 29]

      The percentage of participants with progression of COVID-19 after a single dose of AZD7442 in pediatric participants will be evaluated.

    6. Cohort 2 and Cohort 3 (Treatment) - The incidence of COVID-19-related death occurring after dosing with IMP through 90 days [Day 1 to Day 90]

      COVID-19-related death after a single dose of AZD7442 in pediatric participants will be evaluated.

    7. Cohort 3 (Severe COVID-19) - Time to sustained recovery [Day 1 to Day 366 (from the index hospitalization followed by being alive and home for 14 consecutive days)]

      The time to sustained recovery from severe COVID-19 after a single dose of AZD7442 in pediatric participants will be evaluated.

    Other Outcome Measures

    1. Nasal concentrations of AZD7442 at specified time points during the study period when administered as a single IM or IV dose [Post Day 1 to Day 366]

      The concentration of AZD7442 in nasal fluid after a single dose in pediatric participants will be evaluated.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    0 Years to 17 Years
    Sexes Eligible for Study:
    All
    Accepts 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.

    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.

    Participants will receive IM AZD7442 unless they meet any of the following criteria for IV administration:

    • 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.

    • A central IV line. - 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 < 60 days before screening.

    • Post-pubertal females who are pregnant or breast-feeding.

    • History of alcohol or drug abuse or positive urine drug or alcohol screening within the past 2 years.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Long Beach California United States 90806
    2 Research Site Los Angeles California United States 90095
    3 Research Site Stanford California United States 94305
    4 Research Site Aurora Colorado United States 80045
    5 Research Site Washington District of Columbia United States 20007
    6 Research Site Miami Florida United States 33155
    7 Research Site Saint Petersburg Florida United States 33701
    8 Research Site Idaho Falls Idaho United States 83404
    9 Research Site Ann Arbor Michigan United States 48109
    10 Research Site Kansas City Missouri United States 64108
    11 Research Site Stony Brook New York United States 11794
    12 Research Site Providence Rhode Island United States 02903
    13 Research Site Mount Pleasant South Carolina United States 29464
    14 Research Site Bruxelles Belgium 1200
    15 Research Site Leuven Belgium 3000
    16 Research Site Belo Horizonte Brazil 30130-100
    17 Research Site Botucatu Brazil 18610-070
    18 Research Site Porto Alegre Brazil 90035-001
    19 Research Site Frankfurt am Main Germany 60590
    20 Research Site Köln Germany 50924
    21 Research Site Mexico Mexico 14000
    22 Research Site Mérida Mexico 97070
    23 Research Site Esplugues De Llobregat (Barc) Spain 08950
    24 Research Site Madrid Spain 28041
    25 Research Site Dnipropetrovsk Ukraine 49100
    26 Research Site Dnipro Ukraine 49006
    27 Research Site Krivoi Rog Ukraine 49006
    28 Research Site Zaporizhzhia Ukraine 69076
    29 Research Site Edinburgh United Kingdom EH9 1LF
    30 Research Site Leeds United Kingdom LS1 3EX
    31 Research Site London United Kingdom SW17 0RE
    32 Research Site Manchester United Kingdom M13 9WL
    33 Research Site Newcastle-upon-Tyne United Kingdom NE1 4LP
    34 Research Site Paddington United Kingdom W2 1NY
    35 Research Site Southampton United Kingdom SO16 6YD

    Sponsors and Collaborators

    • AstraZeneca

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT05281601
    Other Study ID Numbers:
    • D8850C00006
    • 2021-006056-13
    First Posted:
    Mar 16, 2022
    Last Update Posted:
    Jul 26, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by AstraZeneca
    AZD7442
    Monoclonal antibodies (mAb)
    COVID-19
    EVUSHELD

    Study Results

    No Results Posted as of Jul 26, 2022