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

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

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.

Study Overview

• Status: Completed
• Conditions: Corona Virus Disease
• Intervention / Treatment: Biological: AZD7442; Biological: AZD8895 (clonal cell line material); Biological: AZD1061 (clonal cell line material); Biological: AZD8895 (cell pool material); Biological: AZD1061 (cell pool material)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 224
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Research Site
    • Cullman, Alabama, United States, 35055
      • Research Site
  • Arizona
    • Scottsdale, Arizona, United States, 85260
      • Research Site
  • California
    • Chula Vista, California, United States, 91911
      • Research Site
    • La Mesa, California, United States, 91942
      • Research Site
    • Long Beach, California, United States, 90806
      • Research Site
    • North Hollywood, California, United States, 91606
      • Research Site
  • Florida
    • Edgewater, Florida, United States, 32132
      • Research Site
    • Lake Worth, Florida, United States, 33462
      • Research Site
    • Orlando, Florida, United States, 320919
      • Research Site
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Research Site
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Research Site
  • South Carolina
    • Union, South Carolina, United States, 29379
      • Research Site
  • Texas
    • Houston, Texas, United States, 77058
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUCinf)	The pharmacokinetic (PK [AUCinf]) comparability between AZD7442 administered as a single IM dose (co-formulation) of (AZD8895 + AZD1061) versus two separate IM doses of AZD8895 followed by AZD1061: using clonal cell line material of AZD8895 and AZD1061 was evaluated. The AUCinf comparability between the clonal cell line material and the cell pool material of AZD7442 administered as two separate sequential IM doses of AZD8895 followed by AZD1061 was also evaluated. day*micrograms per milliliter (day*μg/mL)	Predose on Study Day 1 (2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose) and on Study Days 5, 8, 15, 22, 31, 61, 91, 181, 271 and 361
Area Under the Serum Concentration-time Curve From Day Zero to the Last Measurable Concentration (AUClast)	The PK (AUClast) comparability between AZD7442 administered as a single IM dose (co-formulation) of (AZD8895 + AZD1061) versus two separate IM doses of AZD8895 followed by AZD1061: using clonal cell line material of AZD8895 and AZD1061 was evaluated. The AUClast comparability between the clonal cell line material and the cell pool material of AZD7442 administered as two separate sequential IM doses of AZD8895 followed by AZD1061 was also evaluated.	Predose on Study Day 1 (2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose) and on Study Days 5, 8, 15, 22, 31, 61, 91, 181, 271 and 361
Maximum Observed Serum (Peak) Concentration (Cmax)	The PK (Cmax) comparability between AZD7442 administered as a single IM dose (co-formulation) of (AZD8895 + AZD1061) versus two separate IM doses of AZD8895 followed by AZD1061: using clonal cell line material of AZD8895 and AZD1061 was evaluated. The Cmax comparability between the clonal cell line material and the cell pool material of AZD7442 administered as two separate sequential IM doses of AZD8895 followed by AZD1061 was also evaluated.	Predose on Study Day 1 (2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose) and on Study Days 5, 8, 15, 22, 31, 61, 91, 181, 271 and 361

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Maximum Observed Serum Concentration (Tmax)	The 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 were assessed in healthy adult participants.	Predose on Study Day 1 (2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose) and on Study Days 5, 8, 15, 22, 31, 61, 91, 181, 271 and 361
Area Under the Serum Concentration-time Curve From Day Zero to 30 Days Post-dose (AUC0-31d)	The 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 were assessed in healthy adult participants.	Study Day 1 (Predose, 2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose), and on Study Days 5, 8, 15, 22, and 31
Area Under the Serum Concentration-time Curve From Day Zero to 60 Days Post-dose (AUC0-61d)	The 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 were assessed in healthy adult participants.	Study Day 1 (Predose, 2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose), and on Study Days 5, 8, 15, 22, 31 and 61
Area Under the Serum Concentration-time Curve From Day Zero to 90 Days Post-dose (AUC0-91d)	The 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 were assessed in healthy adult participants.	Study Day 1 (Predose, 2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose), and on Study Days 5, 8, 15, 22, 31, 61 and 91
Area Under the Serum Concentration-time Curve From Day Zero to 180 Days Post-dose (AUC0-181d)	The 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 were assessed in healthy adult participants.	Study Day 1 (Predose, 2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose), and on Study Days 5, 8, 15, 22, 31, 61, 91, and 181
Time of Last Quantifiable Concentration (Tlast)	The 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 were assessed in healthy adult participants.	Predose on Study Day 1 (2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose) and on Study Days 5, 8, 15, 22, 31, 61, 91, 181, 271 and 382
Terminal Half-life (t½λz)	The 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 were assessed in healthy adult participants.	Predose on Study Day 1 (2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose) and on Study Days 5, 8, 15, 22, 31, 61, 91, 181, 271 and 361
Apparent Clearance After Extravascular Administration (CL/F)	The 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 were assessed in healthy adult participants.	Predose on Study Day 1 (2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose) and on Study Days 5, 8, 15, 22, 31, 61, 91, 181, 271 and 361
Volume of Distribution Based on Terminal Phase After Extravascular Administration (Vz/F)	The 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 were assessed in healthy adult participants.	Predose on Study Day 1 (2 hours, 4 hours, 8 hours post dose), Study Day 2 (24 hours post dose) and on Study Days 5, 8, 15, 22, 31, 61, 91, 181, 271 and 361
Number of Participants With Adverse Events (AEs)	The safety of AZD7442 when administered 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 in healthy adult participants was assessed.	From Day 1 until Follow-up visit (Day 361)
Number of Participants With Positive Anti-AZD8895 and Anti-AZD1061 Antibodies	The antidrug antibody (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 was assessed in healthy adult participants.	Day 1 (Pre-dose) until Follow-up visit (Day 361)

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

Helpful Links

• Redacted_CSR_Synopsis
• Redacted_CSP
• Redacted_SAP

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2021
• Primary Completion (Actual): July 19, 2023
• Study Completion (Actual): July 19, 2023

Study Registration Dates

• First Submitted: November 24, 2021
• First Submitted That Met QC Criteria: December 20, 2021
• First Posted (Actual): December 22, 2021

Study Record Updates

• Last Update Posted (Estimated): November 25, 2024
• Last Update Submitted That Met QC Criteria: October 4, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Monoclonal antibodies; Adult healthy participants
• Additional Relevant MeSH Terms: Infections; Virus Diseases; Anti-Infective Agents; Antiviral Agents; Cilgavimab and tixagevimab drug combination
• Other Study ID Numbers: D8850C00009

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 requests will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com /ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

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 refer 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 patientlevel 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No