Phase I Double-blind, Placebo-controlled Study of AZD7442

Study identifier:D8850C00005

ClinicalTrials.gov identifier:NCT04896541

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Phase I Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AZD7442 in Healthy Japanese Participants

Medical condition

COVID-19

Phase

Phase 1

Healthy volunteers

Yes

Study drug

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 55 Years

Date

Study Start Date: 16 Mar 2021

Primary Completion Date: 14 Jun 2022

Study Completion Date: 14 Jun 2022

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Prevention

Verification:

Verified 01 Jun 2024 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Location

Research Site

Fukuoka-shi, Japan, 812-0025

Arms	Assigned Interventions
Experimental: AZD7442 Single dose (IM injections or IV administration) of AZD7442 or saline placebo on Day 1.	Biological/Vaccine: AZD7442 300 mg IM(male) Single dose of 300 mg of AZD7442 or saline placebo on Day 1. Biological/Vaccine: AZD7442 600 mg IM (male) Single dose of 600 mg of AZD7442 or saline placebo on Day 1. Biological/Vaccine: AZD7442 300 mg IV (male and female) Single dose of 300 mg of AZD7442 or saline placebo on Day 1. Biological/Vaccine: AZD7442 1000 mg IV (male) Single dose 1000 mg of AZD7442 or saline placebo on Day 1.
Experimental: placebo Single dose (× 2 separate IM injections or IV administration) of AZD7442 or saline placebo on Day 1.	Biological/Vaccine: AZD7442 300 mg IM(male) Single dose of 300 mg of AZD7442 or saline placebo on Day 1. Biological/Vaccine: AZD7442 600 mg IM (male) Single dose of 600 mg of AZD7442 or saline placebo on Day 1. Biological/Vaccine: AZD7442 300 mg IV (male and female) Single dose of 300 mg of AZD7442 or saline placebo on Day 1. Biological/Vaccine: AZD7442 1000 mg IV (male) Single dose 1000 mg of AZD7442 or saline placebo on Day 1.

Arms

Assigned Interventions

Experimental: AZD7442
Single dose (IM injections or IV administration) of AZD7442 or saline placebo on Day 1.

Biological/Vaccine: AZD7442 300 mg IM(male)
Single dose of 300 mg of AZD7442 or saline placebo on Day 1.

Biological/Vaccine: AZD7442 600 mg IM (male)
Single dose of 600 mg of AZD7442 or saline placebo on Day 1.

Biological/Vaccine: AZD7442 300 mg IV (male and female)
Single dose of 300 mg of AZD7442 or saline placebo on Day 1.

Biological/Vaccine: AZD7442 1000 mg IV (male)
Single dose 1000 mg of AZD7442 or saline placebo on Day 1.

Experimental: placebo
Single dose (× 2 separate IM injections or IV administration) of AZD7442 or saline placebo on Day 1.

Biological/Vaccine: AZD7442 300 mg IM(male)
Single dose of 300 mg of AZD7442 or saline placebo on Day 1.

Biological/Vaccine: AZD7442 600 mg IM (male)
Single dose of 600 mg of AZD7442 or saline placebo on Day 1.

Biological/Vaccine: AZD7442 300 mg IV (male and female)
Single dose of 300 mg of AZD7442 or saline placebo on Day 1.

Biological/Vaccine: AZD7442 1000 mg IV (male)
Single dose 1000 mg of AZD7442 or saline placebo on Day 1.

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
First subject enrolled on 16 March 2021 Last subject last visit on 14 June 2022. This study was conducted at one study site in Japan.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Out of 117 enrolled participants, 40 participants were randomised in this study. A total of 6, 6, 12 and 6 participants were randomised to AZD7442 in Cohort 1, Cohort 2, Cohort 3 (sub-cohort 3F and sub-cohort 3M: 6 participants each) and Cohort 4, respectively, and 10 participants were randomised to placebo.

Reporting Groups

	Description
Pooled Placebo	Participants who received placebo in this study.
300 mg AZD7442, IM	Participants who received AZD7442 300 mg via intramuscular injection
600 mg AZD7442, IM	articipants who received AZD7442 300 mg via intramuscular injection
300 mg AZD7442, IV Male	Male participants who received AZD7442 300 mg via intravenous infusion
300 mg AZD7442, IV Female	Female participants who received AZD7442 300 mg via intravenous infusion
1000 mg AZD7442, IV	Participants who received AZD7442 1000 mg via intravenous infusion

Participant Flow: Overall Study

	Pooled Placebo	300 mg AZD7442, IM	600 mg AZD7442, IM	300 mg AZD7442, IV Male	300 mg AZD7442, IV Female	1000 mg AZD7442, IV
STARTED	10	6	6	6	6	6
COMPLETED	10	6	6	6	6	6
NOT COMPLETED	0	0	0	0	0	0

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
Pooled Placebo	Participants who received placebo in this study.
300 mg AZD7442, IM	Participants who received AZD7442 300 mg via intramuscular injection
600 mg AZD7442, IM	articipants who received AZD7442 300 mg via intramuscular injection
300 mg AZD7442, IV Male	Male participants who received AZD7442 300 mg via intravenous infusion
300 mg AZD7442, IV Female	Female participants who received AZD7442 300 mg via intravenous infusion
1000 mg AZD7442, IV	Participants who received AZD7442 1000 mg via intravenous infusion

Baseline Measures

	Pooled Placebo	300 mg AZD7442, IM	600 mg AZD7442, IM	300 mg AZD7442, IV Male	300 mg AZD7442, IV Female	1000 mg AZD7442, IV	Total
Number of Participants [units: Participants]	10	6	6	6	6	6	40
Sex: Female, Male [units: Participants]
Female	2	0	0	0	6	0	8
Male	8	6	6	6	0	6	32
Race (NIH/OMB) [units: Participants]
American Indian or Alaska Native	0	0	0	0	0	0	0
Asian	10	6	6	6	6	6	40
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0
Black or African American	0	0	0	0	0	0	0
White	0	0	0	0	0	0	0
More than one race	0	0	0	0	0	0	0
Unknown or Not Reported	0	0	0	0	0	0	0
Age, Customized [units: Participants]
18-44 years	5	5	3	5	6	5	29
45 years and older	5	1	3	1	0	1	11
Age Continuous [units: Years] Mean ± Standard Deviation	41.3 ± 11.6	31.8 ± 10.5	37.0 ± 14.8	32.3 ± 12.1	24.7 ± 5.2	35.3 ± 12.4	34.5 ± 12.0

Outcome Measures

1. Primary Outcome Measure: AUCinf of AZD8895 [ Time Frame: Day 1 to Day 361 ]

Measure Type	Primary
Measure Name	AUCinf of AZD8895
Measure Description	Area under the serum concentration versus time curve extrapolated to infinity for AZD8895 after receiving a single dose of AZD7442
Time Frame	Day 1 to Day 361
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
300 mg AZD7442, IM	Participants who received AZD7442 300 mg via intramuscular injection
600 mg AZD7442, IM	articipants who received AZD7442 300 mg via intramuscular injection
300 mg AZD7442, IV Male	Male participants who received AZD7442 300 mg via intravenous infusion
300 mg AZD7442, IV Female	Female participants who received AZD7442 300 mg via intravenous infusion
1000 mg AZD7442, IV	Participants who received AZD7442 1000 mg via intravenous infusion

Measured Values

	300 mg AZD7442, IM	600 mg AZD7442, IM	300 mg AZD7442, IV Male	300 mg AZD7442, IV Female	1000 mg AZD7442, IV
Number of Participants Analyzed [units:participants]	6	6	6	6	6
AUCinf of AZD8895 [units: ug*day/mL] Geometric Mean (Geometric Coefficient of Variation)	3110 (14.83%)	4748 (43.00%)	4439 (16.89%)	3909 (12.97%)	12210 (14.13%)

No statistical analysis provided for AUCinf of AZD8895

2. Primary Outcome Measure: Cmax of AZD8895 [ Time Frame: Day 1 to Day 361 ]

Measure Type	Primary
Measure Name	Cmax of AZD8895
Measure Description	Maximum serum concentration of AZD8995 after receiving a single dose of AZD7442
Time Frame	Day 1 to Day 361
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
300 mg AZD7442, IM	Participants who received AZD7442 300 mg via intramuscular injection
600 mg AZD7442, IM	articipants who received AZD7442 300 mg via intramuscular injection
300 mg AZD7442, IV Male	Male participants who received AZD7442 300 mg via intravenous infusion
300 mg AZD7442, IV Female	Female participants who received AZD7442 300 mg via intravenous infusion
1000 mg AZD7442, IV	Participants who received AZD7442 1000 mg via intravenous infusion

Measured Values

	300 mg AZD7442, IM	600 mg AZD7442, IM	300 mg AZD7442, IV Male	300 mg AZD7442, IV Female	1000 mg AZD7442, IV
Number of Participants Analyzed [units:participants]	6	6	6	6	6
Cmax of AZD8895 [units: ug/mL] Geometric Mean (Geometric Coefficient of Variation)	21.10 (18.89%)	39.29 (36.37%)	53.59 (12.39%)	60.52 (8.646%)	171.8 (10.39%)

No statistical analysis provided for Cmax of AZD8895

3. Primary Outcome Measure: AUCinf of AZD1061 [ Time Frame: Day 1 to Day 361 ]

Measure Type	Primary
Measure Name	AUCinf of AZD1061
Measure Description	Area under the serum concentration versus time curve extrapolated to infinity after receiving a single dose of AZD7442
Time Frame	Day 1 to Day 361
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
300 mg AZD7442, IM	Participants who received AZD7442 300 mg via intramuscular injection
600 mg AZD7442, IM	articipants who received AZD7442 300 mg via intramuscular injection
300 mg AZD7442, IV Male	Male participants who received AZD7442 300 mg via intravenous infusion
300 mg AZD7442, IV Female	Female participants who received AZD7442 300 mg via intravenous infusion
1000 mg AZD7442, IV	Participants who received AZD7442 1000 mg via intravenous infusion

Measured Values

	300 mg AZD7442, IM	600 mg AZD7442, IM	300 mg AZD7442, IV Male	300 mg AZD7442, IV Female	1000 mg AZD7442, IV
Number of Participants Analyzed [units:participants]	6	6	6	6	6
AUCinf of AZD1061 [units: ug*day/mL] Geometric Mean (Geometric Coefficient of Variation)	2925 (14.70%)	4292 (47.67%)	4357 (13.62%)	3993 (11.87%)	11780 (15.27%)

No statistical analysis provided for AUCinf of AZD1061

4. Primary Outcome Measure: Cmax of AZD1061 [ Time Frame: Day 1 to Day 361 ]

Measure Type	Primary
Measure Name	Cmax of AZD1061
Measure Description	Maximum serum concentration of AZD1061 after receiving a single dose of AZD7442
Time Frame	Day 1 to Day 361
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
300 mg AZD7442, IM	Participants who received AZD7442 300 mg via intramuscular injection
600 mg AZD7442, IM	articipants who received AZD7442 300 mg via intramuscular injection
300 mg AZD7442, IV Male	Male participants who received AZD7442 300 mg via intravenous infusion
300 mg AZD7442, IV Female	Female participants who received AZD7442 300 mg via intravenous infusion
1000 mg AZD7442, IV	Participants who received AZD7442 1000 mg via intravenous infusion

Measured Values

	300 mg AZD7442, IM	600 mg AZD7442, IM	300 mg AZD7442, IV Male	300 mg AZD7442, IV Female	1000 mg AZD7442, IV
Number of Participants Analyzed [units:participants]	6	6	6	6	6
Cmax of AZD1061 [units: ug/mL] Geometric Mean (Geometric Coefficient of Variation)	21.30 (14.93%)	37.90 (42.84%)	52.79 (12.20%)	59.85 (7.513%)	166.4 (8.631%)

No statistical analysis provided for Cmax of AZD1061

5. Primary Outcome Measure: Tmax of AZD8895 [ Time Frame: Day 1 to Day 361 ]

Measure Type	Primary
Measure Name	Tmax of AZD8895
Measure Description	Time to reach maximum serum concentration of AZD8895
Time Frame	Day 1 to Day 361
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
300 mg AZD7442, IM	Participants who received AZD7442 300 mg via intramuscular injection
600 mg AZD7442, IM	articipants who received AZD7442 300 mg via intramuscular injection
300 mg AZD7442, IV Male	Male participants who received AZD7442 300 mg via intravenous infusion
300 mg AZD7442, IV Female	Female participants who received AZD7442 300 mg via intravenous infusion
1000 mg AZD7442, IV	Participants who received AZD7442 1000 mg via intravenous infusion

Measured Values

	300 mg AZD7442, IM	600 mg AZD7442, IM	300 mg AZD7442, IV Male	300 mg AZD7442, IV Female	1000 mg AZD7442, IV
Number of Participants Analyzed [units:participants]	6	6	6	6	6
Tmax of AZD8895 [units: day] Median (Full Range)	14.04 (5.04 to 14.04)	10.54 (5.04 to 14.03)	0.3333 (0.0104 to 0.3333)	0.0118 (0.0104 to 0.3333)	0.0160 (0.0160 to 0.3333)

No statistical analysis provided for Tmax of AZD8895

Serious Adverse Events

Time Frame	Serious adverse events were collected from the date of signing of informed consent to Day 361 or withdrawal. Other adverse events were collected from the start of investigational drug administration to Day 361 or withdrawal.
Additional Description	The definition of adverse event and/or serious adverse event was same as the definition of the clinicaltrial.gov.

Reporting Groups

	Description
Pooled Placebo	Participants who received placebo in this study.
300 mg AZD7442, IM	Participants who received AZD7442 300 mg via intramuscular injection
600 mg AZD7442, IM	articipants who received AZD7442 300 mg via intramuscular injection
300 mg AZD7442, IV	All male and female participants who received AZD7442 300 mg via intravenous infusion
1000 mg AZD7442, IV	Participants who received AZD7442 1000 mg via intravenous infusion

Serious Adverse Events

	Pooled Placebo	300 mg AZD7442, IM	600 mg AZD7442, IM	300 mg AZD7442, IV	1000 mg AZD7442, IV
Total, serious adverse events
# participants affected / at risk	0/10 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	0/12 (0.00%)	0/6 (0.00%)

Other Adverse Events

Time Frame	Serious adverse events were collected from the date of signing of informed consent to Day 361 or withdrawal. Other adverse events were collected from the start of investigational drug administration to Day 361 or withdrawal.
Additional Description	The definition of adverse event and/or serious adverse event was same as the definition of the clinicaltrial.gov.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Pooled Placebo	Participants who received placebo in this study.
300 mg AZD7442, IM	Participants who received AZD7442 300 mg via intramuscular injection
600 mg AZD7442, IM	articipants who received AZD7442 300 mg via intramuscular injection
300 mg AZD7442, IV	All male and female participants who received AZD7442 300 mg via intravenous infusion
1000 mg AZD7442, IV	Participants who received AZD7442 1000 mg via intravenous infusion

Other Adverse Events

Pooled Placebo

300 mg AZD7442, IM

600 mg AZD7442, IM

300 mg AZD7442, IV

1000 mg AZD7442, IV

Total, other (not including serious) adverse events

# participants affected / at risk

3/10 (30.00%)

2/6 (33.33%)

3/6 (50.00%)

6/12 (50.00%)

1/6 (16.67%)

Infections and infestations

COVID-19¹

# participants affected / at risk

0/10 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

2/12 (16.67%)

1/6 (16.67%)

Infections and infestations

Folliculitis¹

# participants affected / at risk

0/10 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

0/6 (0.00%)

Infections and infestations

Nasopharyngitis¹

# participants affected / at risk

1/10 (10.00%)

0/6 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

0/6 (0.00%)

Immune system disorders

Seasonal allergy¹

# participants affected / at risk

1/10 (10.00%)

0/6 (0.00%)

0/12 (0.00%)

0/6 (0.00%)

Nervous system disorders

Dizziness¹

# participants affected / at risk

0/10 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

0/6 (0.00%)

Nervous system disorders

Headache¹

# participants affected / at risk

0/10 (0.00%)

2/6 (33.33%)

0/6 (0.00%)

1/12 (8.33%)

0/6 (0.00%)

Gastrointestinal disorders

Dental caries¹

# participants affected / at risk

0/10 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

1/6 (16.67%)

Gastrointestinal disorders

Faeces soft¹

# participants affected / at risk

0/10 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

0/6 (0.00%)

Gastrointestinal disorders

Toothache¹

# participants affected / at risk

0/10 (0.00%)

0/6 (0.00%)

0/12 (0.00%)

1/6 (16.67%)

Gastrointestinal disorders

Vomiting¹

# participants affected / at risk

0/10 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

0/6 (0.00%)

Skin and subcutaneous tissue disorders

Eczema¹

# participants affected / at risk

0/10 (0.00%)

0/6 (0.00%)

2/12 (16.67%)

0/6 (0.00%)

Skin and subcutaneous tissue disorders

Hand dermatitis¹

# participants affected / at risk

0/10 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

0/6 (0.00%)

Musculoskeletal and connective tissue disorders

Musculoskeletal stiffness¹

# participants affected / at risk

0/10 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

0/6 (0.00%)

Musculoskeletal and connective tissue disorders

Myalgia¹

# participants affected / at risk

0/10 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

1/12 (8.33%)

0/6 (0.00%)

Renal and urinary disorders

Ureterolithiasis¹

# participants affected / at risk

1/10 (10.00%)

0/6 (0.00%)

0/12 (0.00%)

0/6 (0.00%)

General disorders

Malaise¹

# participants affected / at risk

0/10 (0.00%)

0/6 (0.00%)

1/12 (8.33%)

0/6 (0.00%)

Investigations

Alanine aminotransferase increased¹

# participants affected / at risk

0/10 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

0/6 (0.00%)

Investigations

Blood creatine phosphokinase increased¹

# participants affected / at risk

1/10 (10.00%)

0/6 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

0/6 (0.00%)

Investigations

Gamma-glutamyltransferase increased¹

# participants affected / at risk

0/10 (0.00%)

0/6 (0.00%)

1/6 (16.67%)

0/12 (0.00%)

0/6 (0.00%)

Injury, poisoning and procedural complications

Vaccination complication¹

# participants affected / at risk

0/10 (0.00%)

1/6 (16.67%)

0/6 (0.00%)

0/12 (0.00%)

0/6 (0.00%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA Version 24.0

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Toshiaki Ozaki/Japan project statistician
Organization:	Biometrics, AstraZeneca R&D Japan
Phone	+819019106810
E-mail:	[email protected]

Documents available

CSR Synopsis
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

CSR Synopsis

Trial Results Summaries