Back to resultsStudy to Evaluate Pharmacokinetic Comparability Between AZD7442 Co-formulation (AZD8895 + AZD1061) vs AZD8895 and AZD1061 Individually in Adult Healthy Participants
Primary Purpose
Corona Virus Disease
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
AZD7442
AZD8895 (clonal cell line material)
AZD1061 (clonal cell line material)
AZD8895 (cell pool material)
AZD1061 (cell pool material)
Sponsored by
About this trial
This is an interventional treatment trial for Corona Virus Disease focused on measuring Monoclonal antibodies, Adult healthy participants
Eligibility Criteria
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).
Sites / Locations
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Active Comparator
Active Comparator
Arm Label
AZD7442 (co-formulation)
AZD8895 and AZD1061 (clonal cell line material)
AZD8895 and AZD1061 (cell pool material)
Arm Description
Participants will receive single dose of AZD7442 (co-formulation of AZD8895 + AZD1061) on Day 1.
Participants will receive two separate doses of the individual mAbs (AZD8895 and then AZD1061) on Day 1.
Participants will receive two separate doses of the individual mAbs (AZD8895 and then AZD1061) on Day 1.
Outcomes
Primary Outcome Measures
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.
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.
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05166421
Brief Title
Study to Evaluate Pharmacokinetic Comparability Between AZD7442 Co-formulation (AZD8895 + AZD1061) vs AZD8895 and AZD1061 Individually in Adult Healthy Participants
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
November 30, 2021 (Actual)
Primary Completion Date
July 19, 2023 (Actual)
Study Completion Date
July 19, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Corona Virus Disease
Keywords
Monoclonal antibodies, Adult healthy participants
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
225 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AZD7442 (co-formulation)
Arm Type
Experimental
Arm Description
Participants will receive single dose of AZD7442 (co-formulation of AZD8895 + AZD1061) on Day 1.
Arm Title
AZD8895 and AZD1061 (clonal cell line material)
Arm Type
Active Comparator
Arm Description
Participants will receive two separate doses of the individual mAbs (AZD8895 and then AZD1061) on Day 1.
Arm Title
AZD8895 and AZD1061 (cell pool material)
Arm Type
Active Comparator
Arm Description
Participants will receive two separate doses of the individual mAbs (AZD8895 and then AZD1061) on Day 1.
Intervention Type
Biological
Intervention Name(s)
AZD7442
Intervention Description
AZD7442 will be administered via IM route.
Intervention Type
Biological
Intervention Name(s)
AZD8895 (clonal cell line material)
Intervention Description
AZD8895 will be administered via IM route.
Intervention Type
Biological
Intervention Name(s)
AZD1061 (clonal cell line material)
Intervention Description
AZD1061 will be administered via IM route.
Intervention Type
Biological
Intervention Name(s)
AZD8895 (cell pool material)
Intervention Description
AZD8895 will be administered via IM route.
Intervention Type
Biological
Intervention Name(s)
AZD1061 (cell pool material)
Intervention Description
AZD1061 will be administered via IM route.
Primary Outcome Measure Information:
Title
Area under serum concentration-time curve from time zero extrapolated to infinity (AUCinf)
Description
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.
Time Frame
Day 1 until Day 361 (Post-dose)
Title
Area under the serum concentration-time curve from time zero to the last quantifiable concentration (AUClast)
Description
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.
Time Frame
Day 1 until Follow-up visit (Day 361)
Title
Maximum observed serum (peak) concentration (Cmax)
Description
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.
Time Frame
Day 1 until Follow-up visit (Day 361)
Secondary Outcome Measure Information:
Title
Time to reach maximum observed serum concentration (Tmax)
Description
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.
Time Frame
Day 1 until Follow-up visit (Day 361)
Title
Area under the serum concentration-time curve from time zero to 30 days post dose (AUC0-31d)
Description
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.
Time Frame
Day 1 (Pre-dose [Time Zero] and Post-dose) until Day 30 (Post-dose)
Title
Area under the serum concentration-time curve from time zero to 60 days post dose (AUC0-61d)
Description
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.
Time Frame
Day 1 (Pre-dose [Time Zero] and Post-dose) until Day 60 (Post-dose)
Title
Time of last quantifiable serum concentration (tlast)
Description
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.
Time Frame
Day 1 until Follow-up visit (Day 361)
Title
Area under the serum concentration-time curve from time zero to 90 days post dose (AUC0-91d)
Description
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.
Time Frame
Day 1 (Pre-dose [Time Zero] and Post-dose) until Day 90 (Post-dose)
Title
Area under the serum concentration-time curve from time zero to 180 days post dose (AUC0-181d)
Description
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.
Time Frame
Day 1 (Pre-dose [Time Zero] and Post-dose) until Day 180 (Post-dose)
Title
Terminal elimination half-life, estimated as (ln2)/λz (t½λz)
Description
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.
Time Frame
Day 1 until Follow-up visit (Day 361)
Title
Apparent total body clearance after extravascular administration (CL/F)
Description
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.
Time Frame
Day 1 until Follow-up visit (Day 361)
Title
Volume of distribution (apparent) based on terminal phase after extravascular administration (Vz/F)
Description
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.
Time Frame
Day 1 until Follow-up visit (Day 361)
Title
Number of participants with adverse events (AEs)
Description
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.
Time Frame
From Screening (Day -28 to -1) until Follow-up visit (Day 361)
Title
Number of participants with positive anti-AZD8895 and anti-AZD1061 antibodies
Description
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.
Time Frame
Day 1 (Pre-dose) until Follow-up visit (Day 361)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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).
Facility Information:
Facility Name
Research Site
City
Anniston
State/Province
Alabama
ZIP/Postal Code
36207
Country
United States
Facility Name
Research Site
City
Cullman
State/Province
Alabama
ZIP/Postal Code
35055
Country
United States
Facility Name
Research Site
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85260
Country
United States
Facility Name
Research Site
City
Chula Vista
State/Province
California
ZIP/Postal Code
91911
Country
United States
Facility Name
Research Site
City
La Mesa
State/Province
California
ZIP/Postal Code
91942
Country
United States
Facility Name
Research Site
City
Long Beach
State/Province
California
ZIP/Postal Code
90806
Country
United States
Facility Name
Research Site
City
North Hollywood
State/Province
California
ZIP/Postal Code
91606
Country
United States
Facility Name
Research Site
City
Edgewater
State/Province
Florida
ZIP/Postal Code
32132
Country
United States
Facility Name
Research Site
City
Lake Worth
State/Province
Florida
ZIP/Postal Code
33462
Country
United States
Facility Name
Research Site
City
Orlando
State/Province
Florida
ZIP/Postal Code
320919
Country
United States
Facility Name
Research Site
City
Meridian
State/Province
Idaho
ZIP/Postal Code
83642
Country
United States
Facility Name
Research Site
City
Berlin
State/Province
New Jersey
ZIP/Postal Code
08009
Country
United States
Facility Name
Research Site
City
Union
State/Province
South Carolina
ZIP/Postal Code
29379
Country
United States
Facility Name
Research Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77058
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing URL
https://astrazenecagroup-dt.pharmacm.com/DT/Home
Learn more about this trial
Study to Evaluate Pharmacokinetic Comparability Between AZD7442 Co-formulation (AZD8895 + AZD1061) vs AZD8895 and AZD1061 Individually in Adult Healthy Participants
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