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

Study Overview
=================
Brief Summary
-----------------
To evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of AZD7442 in Healthy Chinese Adults. vs. placebo

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.

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

Conditions
-----------------
Coronavirus Disease 2019 (COVID-19), Healthy Volunteer

Intervention / Treatment
-----------------
* Drug: AZD7442 IM
* Drug: Placebo IM
* Drug: AZD7442 IM
* Drug: Placebo IM
* Drug: AZD7442 IV
* Drug: Placebo IV
* Drug: AZD7442 IV
* Drug: Placebo IV


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults 18 to 55 years of age Healthy by medical history, physical examination, and baseline safety laboratory tests Negative results of both SARS-CoV-2 qRT-PCR and serology tests within 14 days prior to randomisation. Contraceptive within 365 days post dosing Exclusion Criteria: 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. 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.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

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

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
cilgavimab, AZD1061, Coronavirus, COVID-19, AZD7442, Evusheld, LAAB, tixagevimab, AZD8895