A Study to Evaluate the Safety and Tolerability of AZD7442 in Healthy Chinese Adults

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

To evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of AZD7442 in Healthy Chinese Adults. vs. placebo

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer; Coronavirus Disease 2019 (COVID-19)
• Intervention / Treatment: Drug: AZD7442 IM; Drug: AZD7442 IM; Drug: Placebo IM; Drug: Placebo IM; Drug: AZD7442 IV; Drug: AZD7442 IV; Drug: Placebo IV; Drug: Placebo IV

Detailed Description

A Phase I Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD7442 in healthy Chinese participants 18 to 55 years of age, approximately 60 participants will be randomised in a 4:1 ratio to either AZD7442 or placebo, administered by intramuscular (IM) injection or intravenous (IV) infusion, and approximately 479 days in duration for each participant.

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Guangzhou, China, 510515
    • Research Site
  • Shanghai, China, 201107
    • 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:

1. Adults 18 to 55 years of age
2. Healthy by medical history, physical examination, and baseline safety laboratory tests
3. Negative results of both SARS-CoV-2 qRT-PCR and serology tests within 14 days prior to randomisation.
4. Contraceptive within 365 days post dosing

Exclusion Criteria:

1. Medical condition:

   • Known hypersensitivity to monoclonal antibody (mAb) or investigational product (IP) component.
   • Acute illness including fever on the day prior to or day of dosing.
   • Any other significant disease increase the risk to participant study.

2. Laboratory related:

   • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > upper limit of normal (ULN), or alkaline phosphatase (ALP) or TBL (total bilirubin) > 1.5 × ULN
   • Serum creatinine > ULN
   • Haemoglobin < lower limit normal (LLN)
   • Platelet count < LLN
   • White blood cell or neutrophil count outside normal reference ranges
   • Other laboratory significantly abnormal in the screening panel that, in the opinion of the investigator, will increase participants risk or might confound analysis of study results.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 300 mg AZD7442 IM; Administration of a single dose of 300 mg AZD7442 (150 mg AZD8895 and 150 mg AZD1061) sequentially by intramuscular (IM) injection.	Drug: AZD7442 IM; In cohort 1, participants will be randomized to receive 300 mg AZD7442 (150 mg AZD8895 and 150 mg AZD1061) administered sequentially as direct gluteal IM injections.; Other Names: AZD7442; Drug: AZD7442 IM; In cohort 2, participants will be randomized to receive 600 mg AZD7442 (300 mg AZD8895 and 300 mg AZD1061) administered sequentially as direct gluteal IM injections.; Other Names: AZD7442
Placebo Comparator: 300mg placebo IM; Administration of placebo with dose match to AZD7442 in the same cohort sequentially by intramuscular (IM) injection.	Drug: Placebo IM; In cohort 1, participants will be randomized to receive placebo with dose match to AZD7442 in the same cohort administered sequentially as direct gluteal IM injections.; Other Names: Placebo; Drug: Placebo IM; In cohort 2, participants will be randomized to receive placebo with dose match to AZD7442 in the same cohort administered sequentially as direct gluteal IM injections.; Other Names: Placebo
Experimental: 600 mg AZD7442 IM; Administration of a single dose of 600 mg AZD7442 (300 mg AZD8895 and 300 mg AZD1061) sequentially by intramuscular (IM) injection.	Drug: AZD7442 IM; In cohort 1, participants will be randomized to receive 300 mg AZD7442 (150 mg AZD8895 and 150 mg AZD1061) administered sequentially as direct gluteal IM injections.; Other Names: AZD7442; Drug: AZD7442 IM; In cohort 2, participants will be randomized to receive 600 mg AZD7442 (300 mg AZD8895 and 300 mg AZD1061) administered sequentially as direct gluteal IM injections.; Other Names: AZD7442
Placebo Comparator: 600mg placebo IM; Administration of placebo with dose match to AZD7442 in the same cohort sequentially by intramuscular (IM) injection.	Drug: Placebo IM; In cohort 1, participants will be randomized to receive placebo with dose match to AZD7442 in the same cohort administered sequentially as direct gluteal IM injections.; Other Names: Placebo; Drug: Placebo IM; In cohort 2, participants will be randomized to receive placebo with dose match to AZD7442 in the same cohort administered sequentially as direct gluteal IM injections.; Other Names: Placebo
Experimental: 300 mg AZD7442 IV; co-administration of a single dose of 300 mg AZD7442 (150 mg AZD8895 and 150 mg AZD1061) by intravenous (IV) infusion.	Drug: AZD7442 IV; In cohort 3, participants will be randomized to receive 300 mg AZD7442 (150 mg AZD8895 and 150 mg AZD1061) mixed in IV bag co-administered as a single IV infusion.; Other Names: AZD7442; Drug: AZD7442 IV; In cohort 4, participants will be randomized to receive 600 mg AZD7442 (300 mg AZD8895 and 300 mg AZD1061) mixed in IV bag co-administered as a single IV infusion.; Other Names: Evusheld
Placebo Comparator: 300mg placebo IV; co-administration of a single dose of placebo in equivalent volume by intravenous (IV) infusion.	Drug: Placebo IV; In cohort 3, participants will be randomized to receive placebo with dose match to AZD7442 in the same cohort as a single IV infusion.; Other Names: Placebo; Drug: Placebo IV; In cohort 4, participants will be randomized to receive placebo with dose match to AZD7442 in the same cohort as a single IV infusion.; Other Names: Placebo
Experimental: 600 mg AZD7442 IV; co-administration of a single dose of 600 mg AZD7442 (300 mg AZD8895 and 300 mg AZD1061) by intravenous (IV) infusion.	Drug: AZD7442 IV; In cohort 3, participants will be randomized to receive 300 mg AZD7442 (150 mg AZD8895 and 150 mg AZD1061) mixed in IV bag co-administered as a single IV infusion.; Other Names: AZD7442; Drug: AZD7442 IV; In cohort 4, participants will be randomized to receive 600 mg AZD7442 (300 mg AZD8895 and 300 mg AZD1061) mixed in IV bag co-administered as a single IV infusion.; Other Names: Evusheld
Placebo Comparator: 600mg placebo IV; co-administration of a single dose of placebo in equivalent volume by intravenous (IV) infusion.	Drug: Placebo IV; In cohort 3, participants will be randomized to receive placebo with dose match to AZD7442 in the same cohort as a single IV infusion.; Other Names: Placebo; Drug: Placebo IV; In cohort 4, participants will be randomized to receive placebo with dose match to AZD7442 in the same cohort as a single IV infusion.; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events (AEs)	To evaluate the safety and tolerability of AZD7442 administered IM or IV to healthy Chinese participants 18 to 55 years of age.	From day 1 to approximately 15 months after administration (through Day 451).
Incidence of serious adverse events (SAEs)	To evaluate the safety and tolerability of AZD7442 administered IM or IV to healthy Chinese participants 18 to 55 years of age.	From day 1 to approximately 15 months after administration (through Day 451).
Incidence of adverse event of special interests (AESIs)	To evaluate the safety and tolerability of AZD7442 administered IM or IV to healthy Chinese participants 18 to 55 years of age.	From day 1 to approximately 15 months after administration (through Day 451).
Number of participants with abnormal laboratory test results	Measurement of white blood cell (WBC) count, red blood cell (RBC) count.	From day 1 to approximately 15 months after administration (through Day 451).
Number of participants with abnormal laboratory test results	Measurement of sodium, potassium, urea/blood urea nitrogen (BUN), calcium, phosphate, glucose, c-reactive protein (CRP).	From day 1 to approximately 15 months after administration (through Day 451).
Number of participants with abnormal Coagulation test results	Measurement of prothrombin time, activated partial thrombin time (aPTT).	From day 1 to approximately 15 months after administration (through Day 451).
Number of participants with abnormal urinalysis	Measurement of glucose, protein, and blood.	From day 1 to approximately 15 months after administration (through Day 451).
Number of participants with abnormal ECG readings	Results for PR interval, QRS duration, QT interval, QTcF interval, and RR interval will be analyzed.	From day 1 to approximately 15 months after administration (through Day 451).
Number of participants with abnormal vital signs	Measurement of systolic blood pressure (mm Hg), diastolic blood pressure (mm Hg).	From day 1 to approximately 15 months after administration (through Day 451).
Number of participants with abnormal laboratory test results	Measurement of neutrophils absolute count, lymphocytes absolute count, monocytes absolute count, eosinophils absolute count, Platelets, Reticulocytes absolute count.	From day 1 to approximately 15 months after administration (through Day 451).
Number of participants with abnormal laboratory test results	Measurement of haemoglobin (Hb).	From day 1 to approximately 15 months after administration (through Day 451).
Number of participants with abnormal laboratory test results	Measurement of haematocrit (HCT).	From day 1 to approximately 15 months after administration (through Day 451).
Number of participants with abnormal laboratory test results	Measurement of mean corpuscular volume (MCV).	From day 1 to approximately 15 months after administration (through Day 451).
Number of participants with abnormal laboratory test results	Measurement of mean corpuscular haemoglobin (MCH).	From day 1 to approximately 15 months after administration (through Day 451).
Number of participants with abnormal laboratory test results	Measurement of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transpeptidase (GGT), creatine kinase.	From day 1 to approximately 15 months after administration (through Day 451).
Number of participants with abnormal laboratory test results	Measurement of creatinine, total bilirubin, conjugated bilirubin.	From day 1 to approximately 15 months after administration (through Day 451).
Number of participants with abnormal laboratory test results	Measurement of albumin.	From day 1 to approximately 15 months after administration (through Day 451).
Number of participants with abnormal Coagulation test results	Measurement of international normalised ratio (INR).	From day 1 to approximately 15 months after administration (through Day 451).
Number of participants with abnormal ECG readings	Results for heart rate will be analyzed.	From day 1 to approximately 15 months after administration (through Day 451).
Number of participants with abnormal vital signs	Measurement of pulse rate (beats per minute), respiratory rate (breaths per minute).	From day 1 to approximately 15 months after administration (through Day 451).
Number of participants with abnormal vital signs	Measurement of body temperature (in degree Celsius).	From day 1 to approximately 15 months after administration (through Day 451).

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): October 9, 2021
• Primary Completion (Actual): November 27, 2021
• Study Completion (Actual): January 16, 2023

Study Registration Dates

• First Submitted: June 9, 2022
• First Submitted That Met QC Criteria: June 24, 2022
• First Posted (Actual): June 29, 2022

Study Record Updates

• Last Update Posted (Actual): March 31, 2023
• Last Update Submitted That Met QC Criteria: March 30, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Coronavirus; COVID-19; Evusheld; AZD7442; LAAB; tixagevimab; AZD8895; cilgavimab; AZD1061
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Coronavirus Infections
• Other Study ID Numbers: D8850C00007

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
• 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