Clinical trial NCT05281601: AZD7442 Pharmacokinetics, Pharmacodynamics, and Safety Evaluation in Pediatrics
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: SARS-CoV-2
Keywords: AZD7442
Monoclonal antibodies (mAb)
COVID-19
EVUSHELD
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2022-03-16
Enrollment: 46
Sex: ALL
Minimum age (years): 0
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Serum Concentrations of AZD7442
timeFrame: 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
measure: Maximum Serum Concentration (Cmax)
timeFrame: Day 1 to Day 366 or early discontinuation visit (approximately [approx.] 24 months)
measure: Time to Reach Maximum Serum Concentration (Tmax)
timeFrame: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
measure: Terminal Half-life (t1/2)
timeFrame: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
measure: Area Under the Serum Concentration Versus Time Curve From Time Zero to Time of Last Measurable Concentration (AUC0-last)
timeFrame: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
measure: Area Under the Serum Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf)
timeFrame: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
measure: Time to Last Measurable Concentration (Tlast)
timeFrame: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
measure: Percentage of AUC0-inf Extrapolated to Infinity (% AUCex)
timeFrame: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
measure: Apparent Total Clearance (CL/F)
timeFrame: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
measure: Apparent Volume of Distribution Based on Terminal Phase (Vz/F)
timeFrame: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
measure: Systemic Clearance (CL)
timeFrame: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
measure: Volume of Distribution at Steady State (Vss)
timeFrame: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
measure: Number of Participants With Adverse Events (AE)
timeFrame: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
measure: Number of Participants With Adverse Event of Special Interest (AESI)
timeFrame: Day 1 to day 366 or early discontinuation visit (approx. 24 months)
Secondary outcomes:
measure: Number of Participants With Positive Antidrug Antibodies (ADA) Result to AZD7442.
timeFrame: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
measure: Cohort 2 - Percentage of Participants With Progression of COVID-19 Through Day 29
timeFrame: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
measure: Cohort 2 - Number of Participants With COVID-19 Related Death Occurring After Dosing With IMP Through 90 Days
timeFrame: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
measure: Titre of SARS-CoV-2 Neutralizing Antibodies
timeFrame: Day 31 to Day 366 or early discontinuation visit (approx. 24 months)
measure: Cohort 1 (Prophylaxis) - Number of Participants With SARS-CoV-2 Infections
timeFrame: Day 1 to Day 366 or early discontinuation visit (approx. 24 months)
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Research Site
state: California
city: Aurora
country: United States
facility: Research Site
state: Colorado
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: Idaho Falls
country: United States
facility: Research Site
state: Idaho
city: Stony Brook
country: United States
facility: Research Site
state: New York
city: Providence
country: United States
facility: Research Site
state: Rhode Island
city: Mount Pleasant
country: United States
facility: Research Site
state: South Carolina
city: Leuven
country: Belgium
facility: Research Site
city: Belo Horizonte
country: Brazil
facility: Research Site
city: Frankfurt am Main
country: Germany
facility: Research Site
city: Southampton
country: United Kingdom
facility: Research Site
Study officials:
References: