Dose Exploration Intramuscular/Intravenous Prophylaxis Pharmacokinetic Exposure Response Study

Study Overview
=================
Brief Summary
-----------------
This is a dose exploration study to evaluate the safety and pharmacokinetics (PK) of AZD3152 in healthy adult male and female participants, across different dose levels and routes of administration (ie, Intramuscular [IM] injection and Intravenous [IV] infusion).

Detailed Description
-----------------
The study will be conducted in the United States of America. Eligible healthy participants will be randomized to receive either AZD3152 or placebo administered IM or IV, across 5 fixed-dose cohorts. Participants will receive a single dose of AZD3152/placebo. Cohort 1: Dose X of AZD3152 or placebo, as an IM injection Cohort 2: Dose X of AZD3152 or placebo, administered IV Cohort 3: Dose Y of AZD3152 or placebo, as an IM injection Cohort 4: Dose Y of AZD3152 or placebo, administered IV Cohort 5: Dose Z of AZD3152 or placebo, administered IV The study will comprise of: A Screening Period of maximum 28 days. A Treatment Period of one Day. A Follow-up Period of 12 months after study intervention (Day 365).

Official Title
-----------------
A Phase I, Randomized, Safety and Pharmacokinetics Study of AZD3152 in Healthy Adults (Little DIPPER)

Conditions
-----------------
COVID-19

Intervention / Treatment
-----------------
* Drug: AZD3152
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy male or female participants. Participants have suitable veins for cannulation or repeated venipuncture. Negative SARS-CoV-2 RT-PCR or SARS-CoV-2 rapid antigen test result at Visit 1. Body weight ≥ 45 kg and ≤ 110 kg and body mass index ≥ 18 and <32 kg/m2 at Screening. Able to complete the Follow-up Period up to Day 365 as required by the protocol. Exclusion Criteria: History of any clinically important disease or disorder. Receipt of any immunoglobulin (either COVID-19 or non-COVID related) or blood products within 6 months prior to Day 1. Receipt of an EVUSHELD monoclonal antibody (mAb) against SARS-CoV-2 within last 15 months before Day 1. Receipt of a COVID-19 vaccine within 14 days prior to Visit 1. SARS-CoV-2 infection within one month prior to Visit 1 (confirmed either by laboratory testing or a rapid test [including at-home testing]). Women who are pregnant, lactating, or of childbearing potential and not using a highly effective method of contraception or abstinence from at least 4 weeks prior to study intervention administration and until at least 6 months after study intervention administration. Known or suspected congenital or acquired immunodeficiency, or receipt of immunosuppressive therapy, Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of study intervention. This includes any acute (time-limited) or febrile (temperature ≥ 38.0°C [100.4ºF]) illness/infection on day prior to or day of planned dosing; participants excluded for transient acute illness may be dosed if illness resolves within the Screening Period or may be rescreened once. Any abnormal laboratory values as described in protocol. Any known HIV or hepatitis B or C infection at Screening. History of alcohol or substance abuse that in the opinion of the Investigator might interfere with the trial conduct or completion. Known hypersensitivity to AZD3152. Previous hypersensitivity or severe adverse reaction following administration of a mAb.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD3152 Dose X (IM)<br>Participants will receive dose X of AZD3152 on Day 1 as a single IM injection. | Drug: AZD3152<br>* AZD3152 will be administered via IM injection or IV infusion, as per the assigned arms.<br>|
| Experimental: AZD3152 Dose X (IV)<br>Participants will receive dose X of AZD3152 on Day 1 as an IV infusion. | Drug: AZD3152<br>* AZD3152 will be administered via IM injection or IV infusion, as per the assigned arms.<br>|
| Experimental: AZD3152 Dose Y (IM)<br>Participants will receive dose Y of AZD3152 on Day 1 as 2 sequential IM injections. | Drug: AZD3152<br>* AZD3152 will be administered via IM injection or IV infusion, as per the assigned arms.<br>|
| Experimental: AZD3152 Dose Y (IV)<br>Participants will receive dose Y of AZD3152 on Day 1 as an IV infusion. | Drug: AZD3152<br>* AZD3152 will be administered via IM injection or IV infusion, as per the assigned arms.<br>|
| Experimental: AZD3152 Dose Z (IV)<br>Participants will receive dose Z of AZD3152 on Day 1 as an IV infusion. | Drug: AZD3152<br>* AZD3152 will be administered via IM injection or IV infusion, as per the assigned arms.<br>|
| Placebo Comparator: Pooled placebo<br>Participant will receive placebo on Day 1 either via IM injection or IV infusion. | Other: Placebo<br>* Placebo is a matching volume of 0.9% sodium chloride, will be administered via IM injection or IV infusion, as per the assigned arms.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse event | Evaluation of the safety of IM or IV administration of AZD3152 will be done. | Until Day 91 | 
| Number of participants with serious adverse event | Evaluation of the safety of IM or IV administration of AZD3152 will be done. | Until Day 365 or early discontinuation visit (EDV [approximately 19 months]) | 
| Number of participants with adverse event of special interest | Evaluation of the safety of IM or IV administration of AZD3152 will be done. | Until Day 365 or EDV (approximately 19 months) | 
| Serum concentration of AZD3152 | Pharmacokinetics (PK) characterization of AZD3152 in serum after a single IM or IV dose. | Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months) | 
| Maximum observed concentration (Cmax) of AZD3152 | PK (Cmax) characterization of AZD3152 in serum after a single IM or IV dose. | Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months) | 
| Time to reach maximum observed concentration (tmax) of AZD3152 | PK (tmax) characterization of AZD3152 in serum after a single IM or IV dose. | Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months) | 
| Terminal elimination half-life (t1/2) of AZD3152 | PK (t1/2) characterization of AZD3152 in serum after a single IM or IV dose. | Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months) | 
| Area under the serum concentration-curve from 0 to the last quantifiable concentration (AUClast) of AZD3152 | PK (AUClast) characterization of AZD3152 in serum after a single IM or IV dose. | Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months) | 
| Area under concentration-time curve from 0 to infinity (AUCinf) of AZD3152 | PK (AUCinf) characterization of AZD3152 in serum after a single IM or IV dose. | Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months) | 
| Apparent total body clearance (CL/F) of AZD3152 (IM administration only) | PK (CL/F) characterization of AZD3152 in serum after a single IM. | Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months) | 
| Apparent volume of distribution based on terminal phase (Vz/F) of AZD3152 (IM administration only) | PK (Vz/F) characterization of AZD3152 in serum after a single IM. | Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months) | 
| Total body clearance (CL) of AZD3152 (IV administration only) | PK (CL) characterization of AZD3152 in serum after a single IV. | Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months) | 
| Volume of distribution based on terminal phase (Vz) of AZD3152 (IV administration only) | PK (Vz) characterization of AZD3152 in serum after a single IV. | Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months) | 
| Volume of distribution at steady state (Vss) of AZD3152 (IV administration only) | PK (Vss) characterization of AZD3152 in serum after a single IV. | Pre-dose, and Day 1 until Day 365 or EDV (approximately 19 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with anti-drug antibody (ADA) to AZD3152 | Evaluation of ADA responses to AZD3152. | Pre-dose, Days 15, 31, 91, 181, and Day 365 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Coronavirus disease 2019 (COVID-19), Prophylaxis setting