Corona Virus Disease
Conditions
Keywords
Monoclonal antibodies, Adult healthy participants
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.
Interventions
BIOLOGICALAZD7442
AZD7442 will be administered via IM route.
BIOLOGICALAZD8895 (clonal cell line material)
AZD8895 will be administered via IM route.
BIOLOGICALAZD1061 (clonal cell line material)
AZD1061 will be administered via IM route.
BIOLOGICALAZD8895 (cell pool material)
AZD8895 will be administered via IM route.
BIOLOGICALAZD1061 (cell pool material)
AZD1061 will be administered via IM route.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
Yes
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUCinf) | 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) |
| Area Under the Serum Concentration-time Curve From Day Zero to the Last Measurable Concentration (AUClast) | 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. |
| Maximum Observed Serum (Peak) Concentration (Cmax) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Serum Concentration-time Curve From Day Zero to 90 Days Post-dose (AUC0-91d) | 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. |
| Area Under the Serum Concentration-time Curve From Day Zero to 180 Days Post-dose (AUC0-181d) | 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. |
| Time of Last Quantifiable Concentration (Tlast) | 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. |
| Terminal Half-life (t½λz) | 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. |
| Time to Maximum Observed Serum Concentration (Tmax) | 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. |
| Volume of Distribution Based on Terminal Phase After Extravascular Administration (Vz/F) | 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. |
| Number of Participants With Adverse Events (AEs) | 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. |
| Number of Participants With Positive Anti-AZD8895 and Anti-AZD1061 Antibodies | 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. |
| Apparent Clearance After Extravascular Administration (CL/F) | 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. |
| Area Under the Serum Concentration-time Curve From Day Zero to 30 Days Post-dose (AUC0-31d) | 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. |
| Area Under the Serum Concentration-time Curve From Day Zero to 60 Days Post-dose (AUC0-61d) | 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. |
Countries
United States
Participant flow
Recruitment details
The study was conducted between 30-November-2021 (first subject first visit) to 19-July-2023 (last subject last visit).
Pre-assignment details
A total 224 participants were randomized in this study. The screening period was up to 28 days. ICF was signed prior to screening procedures. Subjects received study drug in a randomized order. All study assessments were performed as per the schedule of assessments.
Participants by arm
| Arm | Count |
|---|---|
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) Participants received AZD7442 as a single intramuscular (IM) dose (co-formulation of AZD8895 + AZD1061) (clonal cell line material) on Day 1. | 76 |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (clonal cell line material) on Day 1. | 72 |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (cell pool material) on Day 1. | 76 |
| Total | 224 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 4 | 1 | 7 |
| Overall Study | Other | 3 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 5 | 3 | 6 |
Baseline characteristics
| Characteristic | Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Total |
|---|---|---|---|---|
| Age, Continuous | 42.6 Years STANDARD_DEVIATION 14.1 | 42.4 Years STANDARD_DEVIATION 15.8 | 41.0 Years STANDARD_DEVIATION 15.2 | 42.0 Years STANDARD_DEVIATION 15 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 14 Participants | 13 Participants | 39 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 64 Participants | 58 Participants | 63 Participants | 185 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 4 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 22 Participants | 19 Participants | 15 Participants | 56 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) White | 50 Participants | 49 Participants | 54 Participants | 153 Participants |
| Sex: Female, Male Female | 30 Participants | 33 Participants | 33 Participants | 96 Participants |
| Sex: Female, Male Male | 46 Participants | 39 Participants | 43 Participants | 128 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 76 | 0 / 72 | 0 / 76 |
| other Total, other adverse events | 2 / 76 | 8 / 72 | 10 / 76 |
| serious Total, serious adverse events | 2 / 76 | 0 / 72 | 1 / 76 |
Outcome results
Primary
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)
Time frame: 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
Population: The PK analysis set consisted of all participants in the safety analysis set who received IMP and had evaluable serum PK data, with no important protocol deviations thought to impact on the analysis of the PK data. Here, 'number of participants analyzed' specifies all participants who were evaluated for this outcome measure and 'number analyzed in each row' signifies the participants with available data that were analyzed for each drug for this outcome measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUCinf) | AZD8895 | 2357 day*μg/mL | Geometric Coefficient of Variation 42.72 |
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUCinf) | AZD7442 | 4642 day*μg/mL | Geometric Coefficient of Variation 43.12 |
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUCinf) | AZD1061 | 2326 day*μg/mL | Geometric Coefficient of Variation 42.69 |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUCinf) | AZD8895 | 2634 day*μg/mL | Geometric Coefficient of Variation 37.13 |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUCinf) | AZD1061 | 2333 day*μg/mL | Geometric Coefficient of Variation 43.42 |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUCinf) | AZD7442 | 4980 day*μg/mL | Geometric Coefficient of Variation 38.96 |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUCinf) | AZD7442 | 4666 day*μg/mL | Geometric Coefficient of Variation 41.06 |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUCinf) | AZD1061 | 2255 day*μg/mL | Geometric Coefficient of Variation 41.7 |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUCinf) | AZD8895 | 2405 day*μg/mL | Geometric Coefficient of Variation 41.42 |
Comparison: Statistical Comparison of AUCinf of AZD744290% CI: [0.8458, 1.0403]
Comparison: Statistical Comparison of AUCinf of AZD744290% CI: [0.898, 1.1066]
Comparison: Statistical Comparison of AUCinf of AZD744290% CI: [0.9579, 1.179]
Comparison: Statistical Comparison of AUCinf of AZD889590% CI: [0.8107, 0.9974]
Comparison: Statistical Comparison of AUCinf of AZD889590% CI: [0.8854, 1.0905]
Comparison: Statistical Comparison of AUCinf of AZD889590% CI: [0.9853, 1.212]
Comparison: Statistical Comparison of AUCinf of AZD106190% CI: [0.9029, 1.1161]
Comparison: Statistical Comparison of AUCinf of AZD106190% CI: [0.9288, 1.1503]
Comparison: Statistical Comparison of AUCinf of AZD106190% CI: [0.9258, 1.1451]
Primary
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.
Time frame: 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
Population: The PK analysis set consisted of all participants in the safety analysis set who received IMP and had evaluable serum PK data, with no important protocol deviations thought to impact on the analysis of the PK data. Here, 'number of participants analyzed' specifies all participants who were evaluated for this outcome measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Area Under the Serum Concentration-time Curve From Day Zero to the Last Measurable Concentration (AUClast) | AZD8895 | 2148 day*μg/mL | Geometric Coefficient of Variation 47.37 |
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Area Under the Serum Concentration-time Curve From Day Zero to the Last Measurable Concentration (AUClast) | AZD7442 | 4362 day*μg/mL | Geometric Coefficient of Variation 43.55 |
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Area Under the Serum Concentration-time Curve From Day Zero to the Last Measurable Concentration (AUClast) | AZD1061 | 2191 day*μg/mL | Geometric Coefficient of Variation 43.7 |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Area Under the Serum Concentration-time Curve From Day Zero to the Last Measurable Concentration (AUClast) | AZD8895 | 2464 day*μg/mL | Geometric Coefficient of Variation 36.34 |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Area Under the Serum Concentration-time Curve From Day Zero to the Last Measurable Concentration (AUClast) | AZD7442 | 4685 day*μg/mL | Geometric Coefficient of Variation 38.6 |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Area Under the Serum Concentration-time Curve From Day Zero to the Last Measurable Concentration (AUClast) | AZD1061 | 2204 day*μg/mL | Geometric Coefficient of Variation 43.62 |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Area Under the Serum Concentration-time Curve From Day Zero to the Last Measurable Concentration (AUClast) | AZD7442 | 4406 day*μg/mL | Geometric Coefficient of Variation 40.41 |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Area Under the Serum Concentration-time Curve From Day Zero to the Last Measurable Concentration (AUClast) | AZD1061 | 2145 day*μg/mL | Geometric Coefficient of Variation 41.27 |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Area Under the Serum Concentration-time Curve From Day Zero to the Last Measurable Concentration (AUClast) | AZD8895 | 2254 day*μg/mL | Geometric Coefficient of Variation 40.54 |
Comparison: Statistical Comparison of AUClast of AZD744290% CI: [0.8512, 1.0421]
Comparison: Statistical Comparison of AUClast of AZD744290% CI: [0.9004, 1.1046]
Comparison: Statistical Comparison of AUClast of AZD744290% CI: [0.9559, 1.173]
Comparison: Statistical Comparison of AUClast of AZD889590% CI: [0.7933, 0.9788]
Comparison: Statistical Comparison of AUClast of AZD889590% CI: [0.8633, 1.0674]
Comparison: Statistical Comparison of AUClast of AZD889590% CI: [0.9796, 1.2116]
Comparison: Statistical Comparison of AUClast of AZD106190% CI: [0.9061, 1.118]
Comparison: Statistical Comparison of AUClast of AZD106190% CI: [0.9257, 1.1446]
Comparison: Statistical Comparison of AUClast of AZD106190% CI: [0.9196, 1.1373]
Primary
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.
Time frame: 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
Population: The PK analysis set consisted of all participants in the safety analysis set who received IMP and had evaluable serum PK data, with no important protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Maximum Observed Serum (Peak) Concentration (Cmax) | AZD1061 | 18.95 Micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 42.15 |
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Maximum Observed Serum (Peak) Concentration (Cmax) | AZD7442 | 37.60 Micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 40.64 |
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Maximum Observed Serum (Peak) Concentration (Cmax) | AZD8895 | 18.69 Micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 41.33 |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Maximum Observed Serum (Peak) Concentration (Cmax) | AZD8895 | 19.25 Micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 37.01 |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Maximum Observed Serum (Peak) Concentration (Cmax) | AZD1061 | 17.29 Micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 47.17 |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Maximum Observed Serum (Peak) Concentration (Cmax) | AZD7442 | 36.48 Micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 40.28 |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Maximum Observed Serum (Peak) Concentration (Cmax) | AZD7442 | 37.76 Micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 33.64 |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Maximum Observed Serum (Peak) Concentration (Cmax) | AZD1061 | 18.53 Micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 36.49 |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Maximum Observed Serum (Peak) Concentration (Cmax) | AZD8895 | 19.37 Micrograms per milliliter (μg/mL) | Geometric Coefficient of Variation 33.26 |
Comparison: Statistical Comparison of Cmax of AZD744290% CI: [0.9451, 1.1243]
Comparison: Statistical Comparison of Cmax of AZD744290% CI: [0.9112, 1.0822]
Comparison: Statistical Comparison of Cmax of AZD744290% CI: [0.8833, 1.0507]
Comparison: Statistical Comparison of Cmax of AZD889590% CI: [0.8894, 1.0582]
Comparison: Statistical Comparison of Cmax of AZD889590% CI: [0.8835, 1.0494]
Comparison: Statistical Comparison of Cmax of AZD889590% CI: [0.91, 1.0826]
Comparison: Statistical Comparison of Cmax of AZD106190% CI: [0.9992, 1.2057]
Comparison: Statistical Comparison of Cmax of AZD106190% CI: [0.929, 1.119]
Comparison: Statistical Comparison of Cmax of AZD106190% CI: [0.8457, 1.0203]
Secondary
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.
Time frame: 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
Population: The PK analysis set consisted of all participants in the safety analysis set who received IMP and had evaluable serum PK data, with no important protocol deviations thought to impact on the analysis of the PK data. Here, 'number of participants analyzed' specifies all participants who were evaluated for this outcome measure and 'number analyzed in each row' signifies the participants with available data that were analyzed for each drug for this outcome measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Apparent Clearance After Extravascular Administration (CL/F) | AZD1061 | 0.06450 Liter per day (L/day) | Geometric Coefficient of Variation 42.69 |
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Apparent Clearance After Extravascular Administration (CL/F) | AZD8895 | 0.06364 Liter per day (L/day) | Geometric Coefficient of Variation 42.72 |
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Apparent Clearance After Extravascular Administration (CL/F) | AZD7442 | 0.06462 Liter per day (L/day) | Geometric Coefficient of Variation 43.12 |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Apparent Clearance After Extravascular Administration (CL/F) | AZD1061 | 0.06431 Liter per day (L/day) | Geometric Coefficient of Variation 43.42 |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Apparent Clearance After Extravascular Administration (CL/F) | AZD7442 | 0.06024 Liter per day (L/day) | Geometric Coefficient of Variation 38.96 |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Apparent Clearance After Extravascular Administration (CL/F) | AZD8895 | 0.05695 Liter per day (L/day) | Geometric Coefficient of Variation 37.13 |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Apparent Clearance After Extravascular Administration (CL/F) | AZD1061 | 0.06652 Liter per day (L/day) | Geometric Coefficient of Variation 41.7 |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Apparent Clearance After Extravascular Administration (CL/F) | AZD8895 | 0.06236 Liter per day (L/day) | Geometric Coefficient of Variation 41.42 |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Apparent Clearance After Extravascular Administration (CL/F) | AZD7442 | 0.06429 Liter per day (L/day) | Geometric Coefficient of Variation 41.06 |
Secondary
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.
Time frame: 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
Population: The PK analysis set consisted of all participants in the safety analysis set who received IMP and had evaluable serum PK data, with no important protocol deviations thought to impact on the analysis of the PK data. Here, 'number of participants analyzed' specifies all participants who were evaluated for this outcome measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Area Under the Serum Concentration-time Curve From Day Zero to 180 Days Post-dose (AUC0-181d) | AZD8895 | 1797 day*μg/mL | Geometric Coefficient of Variation 40.54 |
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Area Under the Serum Concentration-time Curve From Day Zero to 180 Days Post-dose (AUC0-181d) | AZD7442 | 3650 day*μg/mL | Geometric Coefficient of Variation 39.01 |
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Area Under the Serum Concentration-time Curve From Day Zero to 180 Days Post-dose (AUC0-181d) | AZD1061 | 1845 day*μg/mL | Geometric Coefficient of Variation 39.46 |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Area Under the Serum Concentration-time Curve From Day Zero to 180 Days Post-dose (AUC0-181d) | AZD8895 | 1981 day*μg/mL | Geometric Coefficient of Variation 33.77 |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Area Under the Serum Concentration-time Curve From Day Zero to 180 Days Post-dose (AUC0-181d) | AZD7442 | 3788 day*μg/mL | Geometric Coefficient of Variation 36.1 |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Area Under the Serum Concentration-time Curve From Day Zero to 180 Days Post-dose (AUC0-181d) | AZD1061 | 1794 day*μg/mL | Geometric Coefficient of Variation 41.11 |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Area Under the Serum Concentration-time Curve From Day Zero to 180 Days Post-dose (AUC0-181d) | AZD7442 | 3655 day*μg/mL | Geometric Coefficient of Variation 36.41 |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Area Under the Serum Concentration-time Curve From Day Zero to 180 Days Post-dose (AUC0-181d) | AZD1061 | 1793 day*μg/mL | Geometric Coefficient of Variation 37.62 |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Area Under the Serum Concentration-time Curve From Day Zero to 180 Days Post-dose (AUC0-181d) | AZD8895 | 1856 day*μg/mL | Geometric Coefficient of Variation 36.27 |
Secondary
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.
Time frame: 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
Population: The PK analysis set consisted of all participants in the safety analysis set who received IMP and had evaluable serum PK data, with no important protocol deviations thought to impact on the analysis of the PK data. Here, 'number of participants analyzed' specifies all participants who were evaluated for this outcome measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Area Under the Serum Concentration-time Curve From Day Zero to 30 Days Post-dose (AUC0-31d) | AZD8895 | 447.0 day*μg/mL | Geometric Coefficient of Variation 44.69 |
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Area Under the Serum Concentration-time Curve From Day Zero to 30 Days Post-dose (AUC0-31d) | AZD7442 | 903.4 day*μg/mL | Geometric Coefficient of Variation 44.41 |
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Area Under the Serum Concentration-time Curve From Day Zero to 30 Days Post-dose (AUC0-31d) | AZD1061 | 453.9 day*μg/mL | Geometric Coefficient of Variation 45.65 |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Area Under the Serum Concentration-time Curve From Day Zero to 30 Days Post-dose (AUC0-31d) | AZD8895 | 468.9 day*μg/mL | Geometric Coefficient of Variation 42.98 |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Area Under the Serum Concentration-time Curve From Day Zero to 30 Days Post-dose (AUC0-31d) | AZD7442 | 887.9 day*μg/mL | Geometric Coefficient of Variation 46.19 |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Area Under the Serum Concentration-time Curve From Day Zero to 30 Days Post-dose (AUC0-31d) | AZD1061 | 415.0 day*μg/mL | Geometric Coefficient of Variation 52.77 |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Area Under the Serum Concentration-time Curve From Day Zero to 30 Days Post-dose (AUC0-31d) | AZD7442 | 914.2 day*μg/mL | Geometric Coefficient of Variation 40.53 |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Area Under the Serum Concentration-time Curve From Day Zero to 30 Days Post-dose (AUC0-31d) | AZD1061 | 449.3 day*μg/mL | Geometric Coefficient of Variation 42.12 |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Area Under the Serum Concentration-time Curve From Day Zero to 30 Days Post-dose (AUC0-31d) | AZD8895 | 461.7 day*μg/mL | Geometric Coefficient of Variation 41.65 |
Secondary
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.
Time frame: 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
Population: The PK analysis set consisted of all participants in the safety analysis set who received IMP and had evaluable serum PK data, with no important protocol deviations thought to impact on the analysis of the PK data. Here, 'number of participants analyzed' specifies all participants who were evaluated for this outcome measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Area Under the Serum Concentration-time Curve From Day Zero to 60 Days Post-dose (AUC0-61d) | AZD1061 | 894.6 day*μg/mL | Geometric Coefficient of Variation 39.09 |
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Area Under the Serum Concentration-time Curve From Day Zero to 60 Days Post-dose (AUC0-61d) | AZD7442 | 1771 day*μg/mL | Geometric Coefficient of Variation 38.28 |
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Area Under the Serum Concentration-time Curve From Day Zero to 60 Days Post-dose (AUC0-61d) | AZD8895 | 871.4 day*μg/mL | Geometric Coefficient of Variation 39.45 |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Area Under the Serum Concentration-time Curve From Day Zero to 60 Days Post-dose (AUC0-61d) | AZD1061 | 826.0 day*μg/mL | Geometric Coefficient of Variation 43.98 |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Area Under the Serum Concentration-time Curve From Day Zero to 60 Days Post-dose (AUC0-61d) | AZD7442 | 1752 day*μg/mL | Geometric Coefficient of Variation 38.42 |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Area Under the Serum Concentration-time Curve From Day Zero to 60 Days Post-dose (AUC0-61d) | AZD8895 | 918.9 day*μg/mL | Geometric Coefficient of Variation 35.9 |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Area Under the Serum Concentration-time Curve From Day Zero to 60 Days Post-dose (AUC0-61d) | AZD1061 | 865.8 day*μg/mL | Geometric Coefficient of Variation 35.33 |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Area Under the Serum Concentration-time Curve From Day Zero to 60 Days Post-dose (AUC0-61d) | AZD7442 | 1757 day*μg/mL | Geometric Coefficient of Variation 33.67 |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Area Under the Serum Concentration-time Curve From Day Zero to 60 Days Post-dose (AUC0-61d) | AZD8895 | 886.9 day*μg/mL | Geometric Coefficient of Variation 33.87 |
Secondary
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.
Time frame: 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
Population: The PK analysis set consisted of all participants in the safety analysis set who received IMP and had evaluable serum PK data, with no important protocol deviations thought to impact on the analysis of the PK data. Here, 'number of participants analyzed' specifies all participants who were evaluated for this outcome measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Area Under the Serum Concentration-time Curve From Day Zero to 90 Days Post-dose (AUC0-91d) | AZD1061 | 1236 day*μg/mL | Geometric Coefficient of Variation 37.94 |
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Area Under the Serum Concentration-time Curve From Day Zero to 90 Days Post-dose (AUC0-91d) | AZD8895 | 1201 day*μg/mL | Geometric Coefficient of Variation 38.59 |
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Area Under the Serum Concentration-time Curve From Day Zero to 90 Days Post-dose (AUC0-91d) | AZD7442 | 2444 day*μg/mL | Geometric Coefficient of Variation 37.2 |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Area Under the Serum Concentration-time Curve From Day Zero to 90 Days Post-dose (AUC0-91d) | AZD8895 | 1283 day*μg/mL | Geometric Coefficient of Variation 33.67 |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Area Under the Serum Concentration-time Curve From Day Zero to 90 Days Post-dose (AUC0-91d) | AZD7442 | 2453 day*μg/mL | Geometric Coefficient of Variation 36.03 |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Area Under the Serum Concentration-time Curve From Day Zero to 90 Days Post-dose (AUC0-91d) | AZD1061 | 1161 day*μg/mL | Geometric Coefficient of Variation 41.27 |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Area Under the Serum Concentration-time Curve From Day Zero to 90 Days Post-dose (AUC0-91d) | AZD7442 | 2430 day*μg/mL | Geometric Coefficient of Variation 32.95 |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Area Under the Serum Concentration-time Curve From Day Zero to 90 Days Post-dose (AUC0-91d) | AZD1061 | 1198 day*μg/mL | Geometric Coefficient of Variation 34.51 |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Area Under the Serum Concentration-time Curve From Day Zero to 90 Days Post-dose (AUC0-91d) | AZD8895 | 1227 day*μg/mL | Geometric Coefficient of Variation 32.85 |
Secondary
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.
Time frame: From Day 1 until Follow-up visit (Day 361)
Population: The safety analysis set included all participants who were randomized and received any amount of IMP.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Number of Participants With Adverse Events (AEs) | Any possibly related AE | 3 Participants |
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Number of Participants With Adverse Events (AEs) | Any severe AE | 1 Participants |
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Number of Participants With Adverse Events (AEs) | Any possibly related SAE | 0 Participants |
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Number of Participants With Adverse Events (AEs) | Any possibly related severe AE | 0 Participants |
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Number of Participants With Adverse Events (AEs) | Any possibly related AESI | 1 Participants |
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Number of Participants With Adverse Events (AEs) | Any AE | 21 Participants |
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Number of Participants With Adverse Events (AEs) | Any AESI | 1 Participants |
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Number of Participants With Adverse Events (AEs) | Any SAE | 2 Participants |
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Number of Participants With Adverse Events (AEs) | Any SAE with outcome death | 0 Participants |
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Number of Participants With Adverse Events (AEs) | Any AE leading to study discontinuation | 0 Participants |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Number of Participants With Adverse Events (AEs) | Any possibly related AE | 1 Participants |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Number of Participants With Adverse Events (AEs) | Any AESI | 1 Participants |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Number of Participants With Adverse Events (AEs) | Any AE leading to study discontinuation | 0 Participants |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Number of Participants With Adverse Events (AEs) | Any possibly related SAE | 0 Participants |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Number of Participants With Adverse Events (AEs) | Any severe AE | 0 Participants |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Number of Participants With Adverse Events (AEs) | Any AE | 21 Participants |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Number of Participants With Adverse Events (AEs) | Any possibly related severe AE | 0 Participants |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Number of Participants With Adverse Events (AEs) | Any SAE with outcome death | 0 Participants |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Number of Participants With Adverse Events (AEs) | Any possibly related AESI | 1 Participants |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Number of Participants With Adverse Events (AEs) | Any SAE | 0 Participants |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Number of Participants With Adverse Events (AEs) | Any possibly related AESI | 0 Participants |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Number of Participants With Adverse Events (AEs) | Any AE | 26 Participants |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Number of Participants With Adverse Events (AEs) | Any SAE | 1 Participants |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Number of Participants With Adverse Events (AEs) | Any severe AE | 0 Participants |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Number of Participants With Adverse Events (AEs) | Any AESI | 0 Participants |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Number of Participants With Adverse Events (AEs) | Any SAE with outcome death | 0 Participants |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Number of Participants With Adverse Events (AEs) | Any AE leading to study discontinuation | 0 Participants |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Number of Participants With Adverse Events (AEs) | Any possibly related AE | 1 Participants |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Number of Participants With Adverse Events (AEs) | Any possibly related SAE | 0 Participants |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Number of Participants With Adverse Events (AEs) | Any possibly related severe AE | 0 Participants |
Secondary
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.
Time frame: Day 1 (Pre-dose) until Follow-up visit (Day 361)
Population: The AZD8895 and AZD1061 ADA Evaluable Analysis Set included participants with at least 1 baseline and 1 post-baseline AZD8895 and AZD1061 ADA measurement. Here, 'number analyzed in each row' signifies the participants with available data that were analyzed for each drug for that outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Number of Participants With Positive Anti-AZD8895 and Anti-AZD1061 Antibodies | AZD8895 | 6 Participants |
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Number of Participants With Positive Anti-AZD8895 and Anti-AZD1061 Antibodies | AZD1061 | 7 Participants |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Number of Participants With Positive Anti-AZD8895 and Anti-AZD1061 Antibodies | AZD8895 | 2 Participants |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Number of Participants With Positive Anti-AZD8895 and Anti-AZD1061 Antibodies | AZD1061 | 2 Participants |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Number of Participants With Positive Anti-AZD8895 and Anti-AZD1061 Antibodies | AZD8895 | 2 Participants |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Number of Participants With Positive Anti-AZD8895 and Anti-AZD1061 Antibodies | AZD1061 | 1 Participants |
Secondary
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.
Time frame: 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
Population: The PK analysis set consisted of all participants in the safety analysis set who received IMP and had evaluable serum PK data, with no important protocol deviations thought to impact on the analysis of the PK data. Here, 'number of participants analyzed' specifies all participants who were evaluated for this outcome measure and 'number analyzed in each row' signifies the participants with available data that were analyzed for each drug for this outcome measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Terminal Half-life (t½λz) | AZD8895 | 77.77 Day | Geometric Coefficient of Variation 36.38 |
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Terminal Half-life (t½λz) | AZD7442 | 75.13 Day | Geometric Coefficient of Variation 36.76 |
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Terminal Half-life (t½λz) | AZD1061 | 74.11 Day | Geometric Coefficient of Variation 34.48 |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Terminal Half-life (t½λz) | AZD8895 | 83.73 Day | Geometric Coefficient of Variation 30.12 |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Terminal Half-life (t½λz) | AZD7442 | 81.22 Day | Geometric Coefficient of Variation 29.11 |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Terminal Half-life (t½λz) | AZD1061 | 79.19 Day | Geometric Coefficient of Variation 27.68 |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Terminal Half-life (t½λz) | AZD7442 | 76.52 Day | Geometric Coefficient of Variation 32.72 |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Terminal Half-life (t½λz) | AZD1061 | 73.71 Day | Geometric Coefficient of Variation 31.06 |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Terminal Half-life (t½λz) | AZD8895 | 79.19 Day | Geometric Coefficient of Variation 33.93 |
Secondary
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.
Time frame: 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
Population: The PK analysis set consisted of all participants in the safety analysis set who received IMP and had evaluable serum PK data, with no important protocol deviations thought to impact on the analysis of the PK data. Here, 'number of participants analyzed' specifies all participants who were evaluated for this outcome measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Time of Last Quantifiable Concentration (Tlast) | AZD8895 | 357.98 Day |
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Time of Last Quantifiable Concentration (Tlast) | AZD7442 | 357.98 Day |
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Time of Last Quantifiable Concentration (Tlast) | AZD1061 | 357.26 Day |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Time of Last Quantifiable Concentration (Tlast) | AZD8895 | 358.02 Day |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Time of Last Quantifiable Concentration (Tlast) | AZD7442 | 358.02 Day |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Time of Last Quantifiable Concentration (Tlast) | AZD1061 | 357.98 Day |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Time of Last Quantifiable Concentration (Tlast) | AZD7442 | 357.16 Day |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Time of Last Quantifiable Concentration (Tlast) | AZD1061 | 357.16 Day |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Time of Last Quantifiable Concentration (Tlast) | AZD8895 | 357.05 Day |
Secondary
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.
Time frame: 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
Population: The PK analysis set consisted of all participants in the safety analysis set who received IMP and had evaluable serum PK data, with no important protocol deviations thought to impact on the analysis of the PK data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Time to Maximum Observed Serum Concentration (Tmax) | AZD7442 | 13.03 Day |
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Time to Maximum Observed Serum Concentration (Tmax) | AZD1061 | 13.95 Day |
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Time to Maximum Observed Serum Concentration (Tmax) | AZD8895 | 13.02 Day |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Time to Maximum Observed Serum Concentration (Tmax) | AZD7442 | 14.00 Day |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Time to Maximum Observed Serum Concentration (Tmax) | AZD1061 | 14.00 Day |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Time to Maximum Observed Serum Concentration (Tmax) | AZD8895 | 13.98 Day |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Time to Maximum Observed Serum Concentration (Tmax) | AZD1061 | 13.87 Day |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Time to Maximum Observed Serum Concentration (Tmax) | AZD8895 | 8.05 Day |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Time to Maximum Observed Serum Concentration (Tmax) | AZD7442 | 8.05 Day |
Secondary
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.
Time frame: 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
Population: The PK analysis set consisted of all participants in the safety analysis set who received IMP and had evaluable serum PK data, with no important protocol deviations thought to impact on the analysis of the PK data. Here, 'number of participants analyzed' specifies all participants who were evaluated for this outcome measure and 'number analyzed in each row' signifies the participants with available data that were analyzed for each drug for this outcome measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Volume of Distribution Based on Terminal Phase After Extravascular Administration (Vz/F) | AZD1061 | 6.852 Liter (L) | Geometric Coefficient of Variation 36.99 |
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Volume of Distribution Based on Terminal Phase After Extravascular Administration (Vz/F) | AZD8895 | 7.129 Liter (L) | Geometric Coefficient of Variation 35.27 |
| Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material) | Volume of Distribution Based on Terminal Phase After Extravascular Administration (Vz/F) | AZD7442 | 6.960 Liter (L) | Geometric Coefficient of Variation 35.71 |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Volume of Distribution Based on Terminal Phase After Extravascular Administration (Vz/F) | AZD1061 | 7.347 Liter (L) | Geometric Coefficient of Variation 37.76 |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Volume of Distribution Based on Terminal Phase After Extravascular Administration (Vz/F) | AZD7442 | 7.058 Liter (L) | Geometric Coefficient of Variation 32.17 |
| Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material) | Volume of Distribution Based on Terminal Phase After Extravascular Administration (Vz/F) | AZD8895 | 6.880 Liter (L) | Geometric Coefficient of Variation 30.92 |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Volume of Distribution Based on Terminal Phase After Extravascular Administration (Vz/F) | AZD8895 | 7.125 Liter (L) | Geometric Coefficient of Variation 24.29 |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Volume of Distribution Based on Terminal Phase After Extravascular Administration (Vz/F) | AZD7442 | 7.098 Liter (L) | Geometric Coefficient of Variation 24.94 |
| Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material) | Volume of Distribution Based on Terminal Phase After Extravascular Administration (Vz/F) | AZD1061 | 7.075 Liter (L) | Geometric Coefficient of Variation 26.48 |