E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10051905 |
E.1.2 | Term | Coronavirus infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To evaluate the serum concentrations of AZD7442 after a single IM or IV dose in pediatric participants.
• To evaluate the safety and tolerability of AZD7442 after a single IM or IV dose in pediatric participants. |
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E.2.2 | Secondary objectives of the trial |
All Cohorts • To evaluate the pharmacodynamics (PD) of AZD7442 after a single IM or IV dose in pediatric participants • To evaluate the immunogenicity profile of AZD7442 after a single IM or IV dose in pediatric participants.
Cohort I (Prophylaxis) • To evaluate the incidence of SARS-CoV-2 infections with or without COVID-19 symptoms after a single IM or IV dose of AZD7442 in pediatric participants.
Cohort 2 and Cohort 3 (Treatment) • To quantify SARS-CoV-2 viral loads after a single IM or IV dose of AZD7442 in pediatric participants. • To evaluate the proportion of participants with progression of COVID-19 after a single IM or IV dose of AZD7442 in pediatric participants. • To evaluate COVID-19-related death after a single IM or IV dose of AZD7442 in pediatric participants.
Cohort 3 (Severe COVID-19) • To evaluate the time to sustained recovery from severe COVID-19 after a single IM or IV dose of AZD7442 in pediatric participants. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Participant must be aged ≥ 29 weeks 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. • 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 before 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 before 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. • ≥ 92% oxygen saturation at rest within 24 hours before Day 1 unless the participant is a regular receiver of chronic supplementary oxygen for a lung condition.
COHORT 3 • Participants hospitalized with COVID-19 between the 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.
ROUTE OF ADMINISTRATION - 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 intravenous (IV) line. Physician considers IV the appropriate route.
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E.4 | Principal exclusion criteria |
MEDICAL CONDITIONS • Cohort 1: Significant infection or other acute illnesses including fever on or the day prior to or day of 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 in an emergency room service 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 mAb. • Co-morbidity requiring surgery within 7 days prior to study entry or is deemed life-threatening within 30 days prior to study entry.
THERAPY PRIOR ENROLLMENT • 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.
OTHERS • History of alcohol or drug abuse within the past 2 years. • Vulnerable persons (ward of the state, kept in detention). |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Serum concentrations of AZD7442 when administered as a single IM or IV dose.
• PK parameters - Maximum serum concentration (Cmax) - Time to reach maximum serum concentration (tmax) - Terminal half-life (t1/2) - Area under the serum concentration versus time curve from time zero to time of last measurable concentration (AUC0-last) - Area under the serum concentration versus time curve extrapolated to infinity (AUC0-inf) - Time to last measurable concentration (tlast) - Percentage of AUC0-inf extrapolated to infinity (% AUCex) PK parameters for IM: - Apparent total clearance (CL/F) - Apparent volume of distribution based on terminal phase (Vz/F) PK parameters for IV: - Systemic clearance (CL) - Volume of distribution at steady state (Vss)
• Model-derived predicted serum AZD7442 concentrations and AUC0-inf.
• Number of participants with adverse events (Treatment Emergent Adverse Events [TEAEs], Serious Adverse Events [SAEs], and Adverse Event of Special Interests [AESIs]). • Safety laboratory parameters (hematology, clinical chemistry, coagulation, and urinalysis); 12 lead safety ECG; vital signs (BP, pulse rate, tympanic membrane temperature, and respiratory rate), and physical examination. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Day 1 to Day 366, Early Discontinuation Visit.
Day 1 to Day 457, Early Discontinuation Visit (Number of participants with adverse events) |
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E.5.2 | Secondary end point(s) |
All Cohorts (Other than Neonates) • Titer of SARS-CoV-2 neutralizing antibodies. • Number of participants with positive/negative antidrug antibody (ADA) result and neutralizing antibodies to AZD7442.
Cohort 1 (Prophylaxis) • Incidence of SARS-CoV-2 infections with and without COVID-19 symptoms.
Cohort 2 and Cohort 3 (Treatment): • Change from baseline to Day 8 in viral load as measured by qRT-PCR. • Proportion of participants with progression of COVID-19 through Day 29. • The incidence of COVID-19-related death occurring after dosing with IMP through 90 days.
Cohort 3 (Severe COVID-19) • Time to sustained recovery. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Day 1 to Day 366, Early Discontinuation Visit.
Day 1 to Day 90 (Cohort 2 and 3 [Treatment] - The incidence of COVID-19-related death occurring after dosing with IMP through 90 days).
Day 1 to Day 457 (Cohort 3 [Severe COVID-19] - Time to sustained recovery). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
This is not a First In Human but, a First In Pediatric Population trial. |
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E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Brazil |
Mexico |
United States |
Spain |
Germany |
Belgium |
Ukraine |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the trial is defined as the last visit of the last subject. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |