Study of AZD3152 Intramuscular Injection or Intravenous Infusion in Healthy Japanese Adult Participants

Study Overview
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Brief Summary
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AZD3152 is being evaluated for administration to prevent COVID-19. This Phase I study will gather important information on the safety and tolerability of AZD3152 as well as relevant data on the PK, PD (as the neutralising responses against SARS-CoV-2) profile and the generation of ADA to AZD3152.

Detailed Description
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This is a Phase I, randomised, double-blind, placebo controlled study evaluating the safety, tolerability, PK and PD of AZD3152 in healthy Japanese adult participants, 18 to 55 years of age. Approximately 24 healthy participants will be randomised at up to 2 study sites.

Official Title
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A Phase I Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AZD3152 in Healthy Japanese Adults

Conditions
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COVID-19, SARS-CoV-2

Intervention / Treatment
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* Biological: AZD3152 (Cohort 1)
* Biological: Placebo (Cohort 1)
* Biological: AZD3152 (Cohort 2)
* Biological: Placebo (Cohort 2)
* Biological: AZD3152 (Cohort 3)
* Biological: Placebo (Cohort 3)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Japanese men and women and 18 to 55 years of age inclusive, at the time of signing the informed consent. No positive results of SARS-CoV-2 NAT and/or rapid antigen tests. Healthy participants by medical history, physical examination, baseline safety laboratory studies, and screening parameters, according to the judgement of the investigators, with no concomitant disease or concomitant medication. ECG without clinically significant abnormalities. Able to complete the Follow-up Period through Day 361 as required by the protocol. Body weight ≥ 45 kg and ≤ 110 kg and BMI ≥ 18.0 to ≤ 30.0 kg/m2. Exclusion Criteria: Known hypersensitivity to any component of the IMP. History of allergic disease or reactions likely to be exacerbated by any component of the IMP. Previous hypersensitivity, infusion related reaction or severe adverse reaction following administration of mAbs. Fever above 38.0°C on day prior to or on day of randomisation/dosing. AST, ALT or serum creatinine above ULN; bilirubin and ALP >1.5 × ULN. Any vaccination except for COVID-19 vaccine (e.g., inactivated influenzae vaccine) planned. SARS CoV-2 or COVID-19: Receipt of a COVID-19 vaccine within 3 months. COVID-19 infection within 3 months prior.

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
Interventional Model Description: This is a Phase I, randomised, double-blind, placebo controlled study evaluating the safety, tolerability, PK and PD of AZD3152 in healthy Japanese adult participants, 18 to 55 years of age. Approximately 24 healthy participants will be randomised at up to 2 study sites in a ratio of 6:2 in each cohort to either AZD3152 or placebo administered IM or IV, across 3 fixed-dose cohorts. To participants who will receive the IMP via IM injection (Cohorts 1 and 2), the IMP will be given as a direct anterolateral thigh IM administration of AZD3152 or placebo. To participants who will receive the IMP via IV infusion (Cohort 3), the IMP will be administered as an IV infusion containing AZD3152 or placebo. The randomisation of Cohort 2 and 3 should be performed sequentially.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 - AZD3152 300 mg IM direct anterolateral thigh injection<br> | Biological: AZD3152 (Cohort 1)<br>* Single dose of AZD3152 300 mg IM on Visit 2 Day 1<br>|
| Placebo Comparator: Cohort 1 - Placebo IM direct anterolateral thigh injection<br> | Biological: Placebo (Cohort 1)<br>* Single dose of Placebo IM on Visit 2 Day 1<br>|
| Experimental: Cohort 2 - AZD3152 600 mg IM direct anterolateral thigh injection<br> | Biological: AZD3152 (Cohort 2)<br>* Single dose of AZD3152 600 mg IM on Visit 2 Day 1<br>|
| Placebo Comparator: Cohort 2 - Placebo direct anterolateral thigh injection<br> | Biological: Placebo (Cohort 2)<br>* Single dose of Placebo IM on Visit 2 Day 1<br>|
| Experimental: Cohort 3 - AZD3152 1200 mg IV administration<br> | Biological: AZD3152 (Cohort 3)<br>* Single dose of AZD3152 1200 mg IV on Visit 2 Day 1<br>|
| Placebo Comparator: Cohort 3 - Placebo IV administration<br> | Biological: Placebo (Cohort 3)<br>* Single dose of Placebo IM on Visit 2 Day 1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the safety and tolerability of AZD3152 - AEs | Occurrence of AEs collected up to Visit 9 (Day 91) | Up to Visit 9 (Day 91) | 
| To evaluate the safety and tolerability of AZD3152 - SAEs, MAAEs, and AESIs | Occurrence of SAEs, MAAEs, and AESIs collected up to Visit 12 (Day 361) | Up to Visit 12 (Day 361) | 
| To evaluate the safety and tolerability of AZD3152 - Blood pressure | The following variables will be collected: Systolic Blood pressure Diastolic Blood pressure | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Pulse rate | Pulse rate will be collected | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Axillary temperature | Axillary temperature will be collected | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Respiratory rate | Respiratory rate will be collected | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval | PR Interval, QRS Duration, QT Interval, QTcF Interval and RR Interval will be recorded | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Heart rate | Heart rate will be recorded | Up to Visit 7 (Day 29) | 
| To characterise the Serum Pharmacokinetics of AZD3152 - Concentration at the end of infusion (Ceoi) (after intravenous only) | AZD3152 concentration over time and Pharmacokinetics parameters | Up to Visit 12 (Day 361) | 
| To characterise the Serum Pharmacokinetics of AZD3152 - Maximum concentration (Cmax) | AZD3152 concentration over time and Pharmacokinetics parameters | Up to Visit 12 (Day 361) | 
| To characterise the Serum Pharmacokinetics of AZD3152 - Time to maximum concentration (tmax) | AZD3152 concentration over time and Pharmacokinetics parameters | Up to Visit 12 (Day 361) | 
| To characterise the Serum Pharmacokinetics of AZD3152 - Terminal half-life (t½) | AZD3152 concentration over time and Pharmacokinetics parameters | Up to Visit 12 (Day 361) | 
| To characterise the Serum Pharmacokinetics of AZD3152 - Area under the concentration-time curve at the last measured time point (AUClast) | AZD3152 concentration over time and Pharmacokinetics parameters | Up to Visit 12 (Day 361) | 
| To characterise the Serum Pharmacokinetics of AZD3152 - Area under the concentration-time curve from time zero extrapolated to infinity (AUCinf) | AZD3152 concentration over time and Pharmacokinetics parameters | Up to Visit 12 (Day 361) | 
| To evaluate the safety and tolerability of AZD3152 - Haematology - White blood cell count | The following will be collected: - White blood cell count | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Haematology - Red blood cell count | The following will be collected: - Red blood cell count | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Haematology - Haemoglobin | The following will be collected: - Haemoglobin | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Haematology - Haematocrit | The following will be collected: - Haematocrit | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Haematology - Mean corpuscular volume | The following will be collected: - Mean corpuscular volume | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Haematology - Mean corpuscular haemoglobin | The following will be collected: - Mean corpuscular haemoglobin | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Haematology - Mean corpuscular haemoglobin concentration | The following will be collected: - Mean corpuscular haemoglobin concentration | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Haematology - Neutrophils absolute count | The following will be collected: - Neutrophils absolute count | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Haematology - Lymphocytes absolute count | The following will be collected: - Lymphocytes absolute count | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Haematology - Monocytes absolute count | The following will be collected: - Monocytes absolute count | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Haematology - Eosinophils absolute count | The following will be collected: - Eosinophils absolute count | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Haematology - Basophils absolute count | The following will be collected: - Basophils absolute count | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Haematology - Platelets | The following will be collected: - Platelets | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Haematology - Reticulocytes absolute count | The following will be collected: - Reticulocytes absolute count | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Serum Clincal Chemistry - Sodium | The following will be collected: - Sodium | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Serum Clincal Chemistry - Potassium | The following will be collected: - Potassium | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Serum Clincal Chemistry - Blood urea nitrogen | The following will be collected: - Blood urea nitrogen | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Serum Clincal Chemistry - Creatinine and estimated glomerular filtration rate | The following will be collected: - Creatinine and estimated glomerular filtration rate | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Serum Clincal Chemistry - Albumin | The following will be collected: - Albumin | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Serum Clincal Chemistry - Calcium | The following will be collected: - Calcium | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Serum Clincal Chemistry - Phosphate | The following will be collected: - Phosphate | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Serum Clincal Chemistry - Glucose | The following will be collected: - Glucose | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Serum Clincal Chemistry - C reactive protein | The following will be collected: - C reactive protein | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Alkaline phosphatase | The following will be collected: - Alkaline phosphatase | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Serum Clincal Chemistry - Alanine aminotransferase | The following will be collected: - Alanine aminotransferase | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Serum Clincal Chemistry - Aspartate aminotransferase | The following will be collected: - Aspartate aminotransferase | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Serum Clincal Chemistry - Gamma glutamyl transpeptidase | The following will be collected: - Gamma glutamyl transpeptidase | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Serum Clincal Chemistry - Total bilirubin | The following will be collected: - Total bilirubin | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Serum Clincal Chemistry - Unconjugated bilirubin | The following will be collected: - Unconjugated bilirubin | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Serum Clincal Chemistry - Conjugated bilirubin | The following will be collected: - Conjugated bilirubin | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Serum Clincal Chemistry - Creatine kinase | The following will be collected: - Creatine kinase | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Serum Clincal Chemistry - Troponin T and I | The following will be collected: - Troponin T and I | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Urinalysis - Glucose | The following will be collected: - Glucose | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Urinalysis - Blood | The following will be collected: - Blood | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Urinalysis - Microscopy | The following will be collected: - Microscopy | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Urinalysis - Protein | The following will be collected: - Protein | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Coagulation - International normalised ratio | The following will be collected: - International normalised ratio | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Coagulation - Activated partial thrombin time | The following will be collected: - Activated partial thrombin time | Up to Visit 7 (Day 29) | 
| To evaluate the safety and tolerability of AZD3152 - Coagulation - Prothrombin time | The following will be collected: - Prothrombin time | Up to Visit 7 (Day 29) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the Anti-Drug Antibody responses to AZD3152 in serum | Incidence of Anti-Drug Antibody to AZD3152 in serum | Up to Visit 12 (Day 361) | 
| The serum neutralising responses against SARS-CoV-2 using geometric mean titer (GMT) and geometric mean fold rise (GMFR) from baseline | Blood samples as neutralising responses against SARS-CoV-2 in serum will be collected | Up to Visit 12 (Day 361) |