Clinical Trials Register

Summary
EudraCT Number:	2021-006056-13
Sponsor's Protocol Code Number:	D8850C00006
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2022-03-28
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Germany - PEI

A.2

EudraCT number

2021-006056-13

A.3

Full title of the trial

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

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A Study to Evaluate the Pharmacokinetics (behavior of drug inside the body), Pharmacodynamics (biochemical and physiological effects of drugs), and Safety of AZD7442 in children aged ≥ 29 Weeks Gestational Age (measure of the age of a pregnancy) to < 18 Years

A.3.2

Name or abbreviated title of the trial where available

TRUST

A.4.1

Sponsor's protocol code number

D8850C00006

A.5.4

Other Identifiers

Name:

Investigational New Drug (IND) number

Number:

150712

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/235/2021

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	AstraZeneca AB
B.1.3.4	Country	Sweden
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	AstraZeneca
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	AstraZeneca AB
B.5.2	Functional name of contact point	Clinical Study Information Centre
B.5.3	Address:
B.5.3.1	Street Address	Södertälje
B.5.3.2	Town/ city	Södertälje
B.5.3.3	Post code	151 85
B.5.3.4	Country	Sweden
B.5.6	E-mail	Information.Center@astrazeneca.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Cilgavimab
D.3.2	Product code	AZD1061
D.3.4	Pharmaceutical form	Solution for injection/infusion
D.3.4.1	Specific paediatric formulation	Yes
D.3.7	Routes of administration for this IMP	Intramuscular use Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Cilgavimab
D.3.9.1	CAS number	2420563-99-9
D.3.9.2	Current sponsor code	AZD1061
D.3.9.3	Other descriptive name	monoclonal antibody (mAb)
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Tixagevimab
D.3.2	Product code	AZD8895
D.3.4	Pharmaceutical form	Solution for injection/infusion
D.3.4.1	Specific paediatric formulation	Yes
D.3.7	Routes of administration for this IMP	Intramuscular use Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Tixagevimab
D.3.9.1	CAS number	2420564-02-7
D.3.9.2	Current sponsor code	AZD8895
D.3.9.3	Other descriptive name	monoclonal antibody (mAb)
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

COVID-19

E.1.1.1

Medical condition in easily understood language

COVID-19

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

E.1.3

Condition being studied is a rare disease

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.

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.

E.2.3

Trial contains a sub-study

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.

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).

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.

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)

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.

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).

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

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.

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

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

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

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

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

The end of the trial is defined as the last visit of the last subject.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

100

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

Yes

F.1.1.2.1

Number of subjects for this age range:

F.1.1.3

Newborns (0-27 days)

Yes

F.1.1.3.1

Number of subjects for this age range:

F.1.1.4

Infants and toddlers (28 days-23 months)

Yes

F.1.1.4.1

Number of subjects for this age range:

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

Yes

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

Yes

F.3.3.4

Nursing women

Yes

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Pediatric participants aged ≥ 29 weeks Gestational Age to < 18 years.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

100

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2022-05-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-07-26

P. End of Trial
P.	End of Trial Status	Completed

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