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

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

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.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: 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)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Fukuoka-shi, Japan, 812-0025
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AZD7442; Single dose (IM injections or IV administration) of AZD7442 or saline placebo on Day 1.	Biological: AZD7442 300 mg IM(male); Single dose of 300 mg of AZD7442 or saline placebo on Day 1.; Biological: AZD7442 600 mg IM (male); Single dose of 600 mg of AZD7442 or saline placebo on Day 1.; Biological: AZD7442 300 mg IV (male and female); Single dose of 300 mg of AZD7442 or saline placebo on Day 1.; Biological: 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: AZD7442 300 mg IM(male); Single dose of 300 mg of AZD7442 or saline placebo on Day 1.; Biological: AZD7442 600 mg IM (male); Single dose of 600 mg of AZD7442 or saline placebo on Day 1.; Biological: AZD7442 300 mg IV (male and female); Single dose of 300 mg of AZD7442 or saline placebo on Day 1.; Biological: AZD7442 1000 mg IV (male); Single dose 1000 mg of AZD7442 or saline placebo on Day 1.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

General Publications

• Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2021
• Primary Completion (Actual): June 14, 2022
• Study Completion (Actual): June 14, 2022

Study Registration Dates

• First Submitted: February 26, 2021
• First Submitted That Met QC Criteria: May 20, 2021
• First Posted (Actual): May 21, 2021

Study Record Updates

• Last Update Posted (Actual): June 27, 2022
• Last Update Submitted That Met QC Criteria: June 24, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: D8850C00005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indeed that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No