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

NCT05166421
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Phase
Phase 1
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Recruitment status
Completed
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Participants
224
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Lead sponsor
AstraZeneca
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Start date
2021-11-30
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Number of sites
14
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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.
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Short title
Study to Evaluate Pharmacokinetic Comparability Between AZD7442 Co-formulation (AZD8895 + AZD1061) vs AZD8895 and AZD1061 Individually in Adult Healthy Participants
clinicaltrials.gov
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
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Control arm
Active comparator
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Registry reports results
Yes
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Listing at source
Listed
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Recruitment status
Completed
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Phase
Phase 1
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Study type
Interventional
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Completion date
2023-07-19
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First posted
2021-12-22
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Registry last updated
2024-11-25
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Primary completion date
2023-07-19
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Start date
2021-11-30
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Actual participants
224
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Participants
224
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Participant count basis
Actual
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Protocol amendments
5
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Randomisation ratio
1:1:1
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Number of sites
14
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Data monitoring committee
No
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Registry sponsor category
Industry
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Lead sponsor
AstraZeneca
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05166421
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ClinicalTrials.gov ID
NCT05166421
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUCinf)

    Timeframe: 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

    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)

  2. Area Under the Serum Concentration-time Curve From Day Zero to the Last Measurable Concentration (AUClast)

    Timeframe: 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

    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.

  3. Maximum Observed Serum (Peak) Concentration (Cmax)

    Timeframe: 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

    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.

  1. Time to Maximum Observed Serum Concentration (Tmax)

    Timeframe: 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

    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.

  2. Area Under the Serum Concentration-time Curve From Day Zero to 30 Days Post-dose (AUC0-31d)

    Timeframe: 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

    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.

  3. Area Under the Serum Concentration-time Curve From Day Zero to 60 Days Post-dose (AUC0-61d)

    Timeframe: 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

    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.

  4. Area Under the Serum Concentration-time Curve From Day Zero to 90 Days Post-dose (AUC0-91d)

    Timeframe: 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

    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.

  5. Area Under the Serum Concentration-time Curve From Day Zero to 180 Days Post-dose (AUC0-181d)

    Timeframe: 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

    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.

  6. Time of Last Quantifiable Concentration (Tlast)

    Timeframe: 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

    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.

  7. Terminal Half-life (t½λz)

    Timeframe: 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

    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.

  8. Apparent Clearance After Extravascular Administration (CL/F)

    Timeframe: 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

    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.

  9. Volume of Distribution Based on Terminal Phase After Extravascular Administration (Vz/F)

    Timeframe: 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

    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.

  10. Number of Participants With Adverse Events (AEs)

    Timeframe: From Day 1 until Follow-up visit (Day 361)

    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.

  11. Number of Participants With Positive Anti-AZD8895 and Anti-AZD1061 Antibodies

    Timeframe: Day 1 (Pre-dose) until Follow-up visit (Day 361)

    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.

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Maximum age
79 Years
Healthy volunteers
Yes

  • 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.

  • 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).
Sources for eligibility
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  • Research SiteAnniston, United States
  • Research SiteCullman, United States
  • Research SiteScottsdale, United States
  • Research SiteChula Vista, United States
  • Research SiteLa Mesa, United States
  • Research SiteLong Beach, United States
  • Research SiteNorth Hollywood, United States
  • Research SiteEdgewater, United States
  • Research SiteLake Worth, United States
  • Research SiteOrlando, United States
  • Research SiteMeridian, United States
  • Research SiteBerlin, United States
  • Research SiteUnion, United States
  • Research SiteHouston, United States
Sources for sites
clinicaltrials.gov

Sources for references
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Related records

Drugs (2)

Lead sponsors (1)