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

Study Overview
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Brief Summary
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AZD7442 mAbs are being evaluated for administration to prevent or treat COVID-19. This Phase I study will gather important information on the safety and tolerability of AZD7442.

Detailed Description
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Severe acute respiratory coronavirus 2 is a novel coronavirus that appears to have first emerged in China in November 2019 causing cases of atypical pneumonia. Since then, the COVID-19 pandemic has caused major disruption to healthcare systems with significant socioeconomic impacts. As of 22 December 2020, the virus had spread to all corners of the globe, involving 218 countries/regions with over 78.00 million confirmed cases reported and more than 1.71 million associated deaths. As a response to the ongoing pandemic, AstraZeneca is developing mAbs to the SARS-CoV-2 spike protein. The SARS-CoV-2 spike protein contains the virus's receptor binding domain, which enables the virus to bind to receptors on human cells. By targeting this region of the virus's spike protein, antibodies can block the virus's attachment to human cells, and, therefore, are expected to block infection. AZD7442, a combination of 2 of these mAbs (AZD8895 and AZD1061), is being evaluated for administration to treat or prevent COVID-19. There are currently one ongoing Phase I study and two ongoing Phase III studies with AZD7442, in addition to this treatment study. Randomization of approximately 40 Japanese participants is planned.

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

Conditions
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COVID-19

Intervention / Treatment
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* Biological: AZD7442 300 mg IM(male)
* Biological: AZD7442 600 mg IM (male)
* Biological: AZD7442 300 mg IV (male and female)
* Biological: AZD7442 1000 mg IV (male)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must be Japanese men and women and 18 to 55 years of age inclusive, at the time of signing the informed consent. Negative results from both SARS-CoV-2 qRT-PCR and serology tests Healthy by medical history, physical examination, and safety laboratory tests, according to the judgement of the investigators Exclusion Criteria: Fever above 37.5°C by the time when the participant is randomised; a participant excluded for transient acute illness may be dosed if the illness resolves by the time of randomisation. History of infection with SARS or MERS Any drug therapy within 7 days prior to Day 1

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD7442<br>Single dose (IM injections or IV administration) of AZD7442 or saline placebo on Day 1. | Biological: AZD7442 300 mg IM(male)<br>* Single dose of 300 mg of AZD7442 or saline placebo on Day 1.<br>Biological: AZD7442 600 mg IM (male)<br>* Single dose of 600 mg of AZD7442 or saline placebo on Day 1.<br>Biological: AZD7442 300 mg IV (male and female)<br>* Single dose of 300 mg of AZD7442 or saline placebo on Day 1.<br>Biological: AZD7442 1000 mg IV (male)<br>* Single dose 1000 mg of AZD7442 or saline placebo on Day 1.<br>|
| Experimental: placebo<br>Single dose (× 2 separate IM injections or IV administration) of AZD7442 or saline placebo on Day 1. | Biological: AZD7442 300 mg IM(male)<br>* Single dose of 300 mg of AZD7442 or saline placebo on Day 1.<br>Biological: AZD7442 600 mg IM (male)<br>* Single dose of 600 mg of AZD7442 or saline placebo on Day 1.<br>Biological: AZD7442 300 mg IV (male and female)<br>* Single dose of 300 mg of AZD7442 or saline placebo on Day 1.<br>Biological: AZD7442 1000 mg IV (male)<br>* Single dose 1000 mg of AZD7442 or saline placebo on Day 1.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse event and serious adverse event | To evaluate the safety and tolerability of AZD7442 administered IV or IM_Adverse event and serious adverse event | Up to Day361 | 
| Pharmacokinetics - Serum Concentration | To evaluate the single-dose PK of AZD7442. | Up to Day361 | 
| Pharmacokinetics - Maximum Serum Concentration | To evaluate the single-dose PK of AZD7442. | Up to Day361 | 
| Pharmacokinetics - Time to Maximum Serum Concentration | To evaluate the single-dose PK of AZD7442. | Up to Day361 | 
| Pharmacokinetics - Area under the plasma concentration-time curve to the last measurable time point | To evaluate the single-dose PK of AZD7442. | Up to Day361 | 
| Pharmacokinetics - Area under the plasma concentration-time curve extrapolated to infinity | To evaluate the single-dose PK of AZD7442. | Up to Day361 | 
| Pharmacokinetics - extravascular systemic clearance | To evaluate the single-dose PK of AZD7442. | Up to 361 | 
| Pharmacokinetics -bioavailability | To evaluate the single-dose PK of AZD7442. | Up to Day361 | 
| Pharmacokinetics -extravascular terminal phase volume of distribution | To evaluate the single-dose PK of AZD7442. | Up to Day361 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The serum neutralizing responses against SARS-CoV-2 using Geometric mean fold rise from baseline | Blood samples as neutralizing responses against SARS-CoV-2 in serum will be collected. | Up to Day361 | 
| ADA responses to the AZD7442 in serum. | Blood samples for determination of ADA in serum will be assayed by bioanalytical test sites, using an appropriately validated bioanalytical method. | Up to Day361 | 
| The serum neutralizing responses against SARS-CoV-2 using Geometric mean titre from baseline | Blood samples as neutralizing responses against SARS-CoV-2 in serum will be collected. | Up to Day361 |