Study to Evaluate Pharmacokinetic Comparability Between AZD7442 Co-formulation (AZD8895 + AZD1061) vs AZD8895 and AZD1061 Individually in Adult Healthy Participants

Study Overview
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Brief Summary
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The study will assess pharmacokinetic (PK) comparability between different formulations of AZD7442, which is a combination of two individual monoclonal antibodies (mAbs), AZD8895 and AZD1061.

Detailed Description
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This is a randomized, open label, three-arm, single dose, parallel group, multi-center, PK comparability study. Eligible healthy participants will be randomized in a 1:1:1 ratio between the 3 treatment groups. Each participant will receive AZD7442 as either a single intramuscular (IM) dose (co-formulation; AZD8895 + AZD1061), or as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) from either clonal cell line material or cell pool material. Following an observation and PK and pharmacodynamic (PD) sample collection, post-dose, participants will be discharged from the Clinical Unit. During the Follow-up Period of approximately 1 year, participants will return as outpatient follow-up visits until Day 361. The total duration of the study for a participant will be approximately 389 days comprising of a Screening Period that can last up to 28 days, Treatment Period of 1 day, and a Follow up Period of 360 days.

Official Title
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Phase 1, Randomized, Open Label, Three-arm, Single Dose, Parallel Group Study to Compare AZD7442 (AZD8895 + AZD1061) Pharmacokinetic Exposure Following Intramuscular Administration as a Co-formulation Versus Administration From Two Separate Vials of the Individual Monoclonal Antibodies in Adult Healthy Participants

Conditions
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Corona Virus Disease

Intervention / Treatment
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* Biological: AZD7442
* Biological: AZD8895 (clonal cell line material)
* Biological: AZD1061 (clonal cell line material)
* Biological: AZD8895 (cell pool material)
* Biological: AZD1061 (cell pool material)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy participants according to medical history, physical examination, and baseline safety laboratory tests. Documented negative results of a Severe Acute Respiratory Syndrome Corona Virus 2 reverse transcriptase polymerase chain reaction (SARS-CoV-2 RT-PCR) test collected ≤ 3 days prior to investigational medicinal drug (IMP) dose administration (Day 1) or a negative rapid SARS-CoV-2 antigen test on Day 1 (pre-dose). Able to complete the Follow-up period up to Day 361 as required by the protocol. Body weight ≥ 50 kg to ≤ 110 kg at screening and a Body mass index ≥ 18.0 to ≤ 30 kg/m^2 at the time of the Screening Visit. Exclusion Criteria: Known history of allergy or reaction to any component of AZD7442 (AZD8895 + AZD1061). History of infection with SARS or Middle East Respiratory Syndrome. Positive SARSCoV-2 result based on available data at screening or at Day 1. Any clinical signs and symptoms consistent with Corona virus disease 2019 (COVID-19), eg, fever, dry cough, dyspnea, sore throat, fatigue, or confirmed infection by appropriate laboratory test within the last 4 weeks prior to screening or on admission. History of clinically significant bleeding disorder. Active infection with hepatitis B or C or positive test for hepatitis C or for hepatitis B surface antigen at screening. Immunodeficiency due to illness, including HIV infection, or due to drugs, including any course of glucocorticoid therapy exceeding 2 weeks of prednisone. Any other significant disease, disorder, or finding that may significantly increase the risk to the participant because of participation in the study Any prior receipt of another mAb indicated for the prevention or treatment of SARS CoV-2 or COVID-19. Receipt of a mAb within 6 months or 5 antibody half-lives. Receipt of a COVID-19 vaccination ≤ 14 days before IMP administration (Day 1) or plan to receive a COVID-19 vaccination ≤ 14 days after IMP dose (such participants can subsequently be included in the study once they have reached > 14 days after their last dose of vaccine).

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD7442 (co-formulation)<br>Participants will receive single dose of AZD7442 (co-formulation of AZD8895 + AZD1061) on Day 1. | Biological: AZD7442<br>* AZD7442 will be administered via IM route.<br>|
| Active Comparator: AZD8895 and AZD1061 (clonal cell line material)<br>Participants will receive two separate doses of the individual mAbs (AZD8895 and then AZD1061) on Day 1. | Biological: AZD8895 (clonal cell line material)<br>* AZD8895 will be administered via IM route.<br>Biological: AZD1061 (clonal cell line material)<br>* AZD1061 will be administered via IM route.<br>|
| Active Comparator: AZD8895 and AZD1061 (cell pool material)<br>Participants will receive two separate doses of the individual mAbs (AZD8895 and then AZD1061) on Day 1. | Biological: AZD8895 (cell pool material)<br>* AZD8895 will be administered via IM route.<br>Biological: AZD1061 (cell pool material)<br>* AZD1061 will be administered via IM route.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under serum concentration-time curve from time zero extrapolated to infinity (AUCinf) | PK (AUCinf) comparability between: a) AZD7442 administered as a single IM dose (co-formulation) (AZD8895 + AZD1061) versus two separate IM doses (AZD8895 and AZD1061) (clonal cell line material and cell pool material of AZD8895 and AZD1061), and b) clonal cell line material versus the cell pool material of AZD7442 administered as two separate sequential IM doses (AZD8895 and AZD1061) of the individual mAbs will be evaluated in healthy adult participants. | Day 1 until Day 361 (Post-dose) | 
| Area under the serum concentration-time curve from time zero to the last quantifiable concentration (AUClast) | PK (AUClast) comparability between: a) AZD7442 administered as a single IM dose (co-formulation) (AZD8895 + AZD1061) versus two separate IM doses (AZD8895 and AZD1061) (clonal cell line material and cell pool material of AZD8895 and AZD1061), and b) clonal cell line material versus the cell pool material of AZD7442 administered as two separate sequential IM doses (AZD8895 and AZD1061) of the individual mAbs will be evaluated in healthy adult participants. | Day 1 until Follow-up visit (Day 361) | 
| Maximum observed serum (peak) concentration (Cmax) | PK (Cmax) comparability between: a) AZD7442 administered as a single IM dose (co-formulation) (AZD8895 + AZD1061) versus two separate IM doses (AZD8895 and AZD1061) (clonal cell line material and cell pool material of AZD8895 and AZD1061), and b) clonal cell line material versus the cell pool material of AZD7442 administered as two separate sequential IM doses (AZD8895 and AZD1061) of the individual mAbs will be evaluated in healthy adult participants. | Day 1 until Follow-up visit (Day 361) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to reach maximum observed serum concentration (Tmax) | PK (Tmax) following administration of AZD7442 as a single IM dose (co-formulation) (AZD8895 + AZD1061) and two separate IM doses (AZD8895 and then AZD1061) (clonal cell line or cell pool material) of the individual mAbs will be assessed in healthy adult participants. | Day 1 until Follow-up visit (Day 361) | 
| Area under the serum concentration-time curve from time zero to 30 days post dose (AUC0-31d) | PK (AUC0-31d) following administration of AZD7442 as a single IM dose (co-formulation) (AZD8895 + AZD1061) and two separate IM doses (AZD8895 and then AZD1061) (clonal cell line or cell pool material) of the individual mAbs will be assessed in healthy adult participants. | Day 1 (Pre-dose [Time Zero] and Post-dose) until Day 30 (Post-dose) | 
| Area under the serum concentration-time curve from time zero to 60 days post dose (AUC0-61d) | PK (AUC0-61d) following administration of AZD7442 as a single IM dose (co-formulation) (AZD8895 + AZD1061) and two separate IM doses (AZD8895 and then AZD1061) (clonal cell line or cell pool material) of the individual mAbs will be assessed in healthy adult participants. | Day 1 (Pre-dose [Time Zero] and Post-dose) until Day 60 (Post-dose) | 
| Time of last quantifiable serum concentration (tlast) | PK (tlast) following administration of AZD7442 as a single IM dose (co-formulation) (AZD8895 + AZD1061) and two separate IM doses (AZD8895 and then AZD1061) (clonal cell line or cell pool material) of the individual mAbs will be assessed in healthy adult participants. | Day 1 until Follow-up visit (Day 361) | 
| Area under the serum concentration-time curve from time zero to 90 days post dose (AUC0-91d) | PK (AUC0-91d) following administration of AZD7442 as a single IM dose (co-formulation) (AZD8895 + AZD1061) and two separate IM doses (AZD8895 and then AZD1061) (clonal cell line or cell pool material) of the individual mAbs will be assessed in healthy adult participants. | Day 1 (Pre-dose [Time Zero] and Post-dose) until Day 90 (Post-dose) | 
| Area under the serum concentration-time curve from time zero to 180 days post dose (AUC0-181d) | PK (AUC0-181d) following administration of AZD7442 as a single IM dose (co-formulation) (AZD8895 + AZD1061) and two separate IM doses (AZD8895 and then AZD1061) (clonal cell line or cell pool material) of the individual mAbs will be assessed in healthy adult participants. | Day 1 (Pre-dose [Time Zero] and Post-dose) until Day 180 (Post-dose) | 
| Terminal elimination half-life, estimated as (ln2)/λz (t½λz) | PK (t½λz) following administration of AZD7442 as a single IM dose (co-formulation) (AZD8895 + AZD1061) and two separate IM doses (AZD8895 and then AZD1061) (clonal cell line or cell pool material) of the individual mAbs will be assessed in healthy adult participants. | Day 1 until Follow-up visit (Day 361) | 
| Apparent total body clearance after extravascular administration (CL/F) | PK (CL/F) following administration of AZD7442 as a single IM dose (co-formulation) (AZD8895 + AZD1061) and two separate IM doses (AZD8895 and then AZD1061) (clonal cell line or cell pool material) of the individual mAbs will be assessed in healthy adult participants. | Day 1 until Follow-up visit (Day 361) | 
| Volume of distribution (apparent) based on terminal phase after extravascular administration (Vz/F) | PK (Vz/F) following administration of AZD7442 as a single IM dose (co-formulation) (AZD8895 + AZD1061) and two separate IM doses (AZD8895 and then AZD1061) (clonal cell line or cell pool material) of the individual mAbs will be assessed in healthy adult participants. | Day 1 until Follow-up visit (Day 361) | 
| Number of participants with adverse events (AEs) | Safety of AZD7442 following administration of AZD7442 as a single IM dose (co-formulation) (AZD8895 + AZD1061) and two separate IM doses (AZD8895 and then AZD1061) (clonal cell line or cell pool material) of the individual mAbs will be assessed in healthy adult participants. | From Screening (Day -28 to -1) until Follow-up visit (Day 361) | 
| Number of participants with positive anti-AZD8895 and anti-AZD1061 antibodies | The ADA responses to AZD7442 in serum following administration of AZD7442 as a single IM dose (co-formulation) (AZD8895 + AZD1061) and two separate IM doses (AZD8895 and then AZD1061) (clonal cell line or cell pool material) of the individual mAbs will be assessed in healthy adult participants. | Day 1 (Pre-dose) until Follow-up visit (Day 361) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Monoclonal antibodies, Adult healthy participants