Trial Outcomes & Findings for Study to Evaluate Pharmacokinetic Comparability Between AZD7442 Co-formulation (AZD8895 + AZD1061) vs AZD8895 and AZD1061 Individually in Adult Healthy Participants (NCT NCT05166421)

NCT ID: NCT05166421

Last Updated: 2024-11-25

Results Overview

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)

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

224 participants

Primary outcome 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

Results posted on

2024-11-25

Participant Flow

The study was conducted between 30-November-2021 (first subject first visit) to 19-July-2023 (last subject last visit).

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.

Participant milestones

Participant milestones
Measure
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.
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.
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.
Overall Study
STARTED
76
72
76
Overall Study
COMPLETED
64
67
62
Overall Study
NOT COMPLETED
12
5
14

Reasons for withdrawal

Reasons for withdrawal
Measure
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.
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.
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.
Overall Study
Other
3
1
1
Overall Study
Withdrawal by Subject
5
3
6
Overall Study
Lost to Follow-up
4
1
7

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material)
n=76 Participants
Participants received AZD7442 as a single intramuscular (IM) dose (co-formulation of AZD8895 + AZD1061) (clonal cell line material) on Day 1.
Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material)
n=72 Participants
Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (clonal cell line material) on Day 1.
Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material)
n=76 Participants
Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (cell pool material) on Day 1.
Total
n=224 Participants
Total of all reporting groups
Age, Continuous
42.6 Years
STANDARD_DEVIATION 14.1 • n=5 Participants
42.4 Years
STANDARD_DEVIATION 15.8 • n=7 Participants
41.0 Years
STANDARD_DEVIATION 15.2 • n=5 Participants
42.0 Years
STANDARD_DEVIATION 15.0 • n=4 Participants
Sex: Female, Male
Female
30 Participants
n=5 Participants
33 Participants
n=7 Participants
33 Participants
n=5 Participants
96 Participants
n=4 Participants
Sex: Female, Male
Male
46 Participants
n=5 Participants
39 Participants
n=7 Participants
43 Participants
n=5 Participants
128 Participants
n=4 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
12 Participants
n=5 Participants
14 Participants
n=7 Participants
13 Participants
n=5 Participants
39 Participants
n=4 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
64 Participants
n=5 Participants
58 Participants
n=7 Participants
63 Participants
n=5 Participants
185 Participants
n=4 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
Race (NIH/OMB)
Asian
2 Participants
n=5 Participants
2 Participants
n=7 Participants
4 Participants
n=5 Participants
8 Participants
n=4 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
Race (NIH/OMB)
Black or African American
22 Participants
n=5 Participants
19 Participants
n=7 Participants
15 Participants
n=5 Participants
56 Participants
n=4 Participants
Race (NIH/OMB)
White
50 Participants
n=5 Participants
49 Participants
n=7 Participants
54 Participants
n=5 Participants
153 Participants
n=4 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
0 Participants
n=7 Participants
2 Participants
n=5 Participants
2 Participants
n=4 Participants
Race (NIH/OMB)
Unknown or Not Reported
2 Participants
n=5 Participants
2 Participants
n=7 Participants
1 Participants
n=5 Participants
5 Participants
n=4 Participants

PRIMARY outcome

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

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.

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)

Outcome measures

Outcome measures
Measure
Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material)
n=63 Participants
Participants received AZD7442 as a single intramuscular (IM) dose (co-formulation of AZD8895 + AZD1061) (clonal cell line material) on Day 1.
Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material)
n=65 Participants
Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (clonal cell line material) on Day 1.
Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material)
n=62 Participants
Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (cell pool material) on Day 1.
Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUCinf)
AZD7442
4642 day*μg/mL
Geometric Coefficient of Variation 43.12
4980 day*μg/mL
Geometric Coefficient of Variation 38.96
4666 day*μg/mL
Geometric Coefficient of Variation 41.06
Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUCinf)
AZD8895
2357 day*μg/mL
Geometric Coefficient of Variation 42.72
2634 day*μg/mL
Geometric Coefficient of Variation 37.13
2405 day*μg/mL
Geometric Coefficient of Variation 41.42
Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUCinf)
AZD1061
2326 day*μg/mL
Geometric Coefficient of Variation 42.69
2333 day*μg/mL
Geometric Coefficient of Variation 43.42
2255 day*μg/mL
Geometric Coefficient of Variation 41.70

PRIMARY outcome

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

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.

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.

Outcome measures

Outcome measures
Measure
Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material)
n=65 Participants
Participants received AZD7442 as a single intramuscular (IM) dose (co-formulation of AZD8895 + AZD1061) (clonal cell line material) on Day 1.
Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material)
n=65 Participants
Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (clonal cell line material) on Day 1.
Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material)
n=62 Participants
Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (cell pool material) on Day 1.
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 43.70
2204 day*μg/mL
Geometric Coefficient of Variation 43.62
2145 day*μg/mL
Geometric Coefficient of Variation 41.27
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
4685 day*μg/mL
Geometric Coefficient of Variation 38.60
4406 day*μg/mL
Geometric Coefficient of Variation 40.41
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
2464 day*μg/mL
Geometric Coefficient of Variation 36.34
2254 day*μg/mL
Geometric Coefficient of Variation 40.54

PRIMARY outcome

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

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.

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.

Outcome measures

Outcome measures
Measure
Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material)
n=71 Participants
Participants received AZD7442 as a single intramuscular (IM) dose (co-formulation of AZD8895 + AZD1061) (clonal cell line material) on Day 1.
Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material)
n=69 Participants
Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (clonal cell line material) on Day 1.
Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material)
n=71 Participants
Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (cell pool material) on Day 1.
Maximum Observed Serum (Peak) Concentration (Cmax)
AZD7442
37.60 Micrograms per milliliter (μg/mL)
Geometric Coefficient of Variation 40.64
36.48 Micrograms per milliliter (μg/mL)
Geometric Coefficient of Variation 40.28
37.76 Micrograms per milliliter (μg/mL)
Geometric Coefficient of Variation 33.64
Maximum Observed Serum (Peak) Concentration (Cmax)
AZD8895
18.69 Micrograms per milliliter (μg/mL)
Geometric Coefficient of Variation 41.33
19.25 Micrograms per milliliter (μg/mL)
Geometric Coefficient of Variation 37.01
19.37 Micrograms per milliliter (μg/mL)
Geometric Coefficient of Variation 33.26
Maximum Observed Serum (Peak) Concentration (Cmax)
AZD1061
18.95 Micrograms per milliliter (μg/mL)
Geometric Coefficient of Variation 42.15
17.29 Micrograms per milliliter (μg/mL)
Geometric Coefficient of Variation 47.17
18.53 Micrograms per milliliter (μg/mL)
Geometric Coefficient of Variation 36.49

SECONDARY outcome

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

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.

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.

Outcome measures

Outcome measures
Measure
Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material)
n=71 Participants
Participants received AZD7442 as a single intramuscular (IM) dose (co-formulation of AZD8895 + AZD1061) (clonal cell line material) on Day 1.
Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material)
n=69 Participants
Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (clonal cell line material) on Day 1.
Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material)
n=71 Participants
Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (cell pool material) on Day 1.
Time to Maximum Observed Serum Concentration (Tmax)
AZD7442
13.03 Day
Interval 2.96 to 85.01
14.00 Day
Interval 2.98 to 90.96
8.05 Day
Interval 2.97 to 61.95
Time to Maximum Observed Serum Concentration (Tmax)
AZD8895
13.02 Day
Interval 2.96 to 85.01
13.98 Day
Interval 2.98 to 90.96
8.05 Day
Interval 2.97 to 91.07
Time to Maximum Observed Serum Concentration (Tmax)
AZD1061
13.95 Day
Interval 2.96 to 55.07
14.00 Day
Interval 1.0 to 63.0
13.87 Day
Interval 2.98 to 61.95

SECONDARY outcome

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

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.

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.

Outcome measures

Outcome measures
Measure
Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material)
n=70 Participants
Participants received AZD7442 as a single intramuscular (IM) dose (co-formulation of AZD8895 + AZD1061) (clonal cell line material) on Day 1.
Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material)
n=67 Participants
Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (clonal cell line material) on Day 1.
Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material)
n=68 Participants
Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (cell pool material) on Day 1.
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
887.9 day*μg/mL
Geometric Coefficient of Variation 46.19
914.2 day*μg/mL
Geometric Coefficient of Variation 40.53
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
468.9 day*μg/mL
Geometric Coefficient of Variation 42.98
461.7 day*μg/mL
Geometric Coefficient of Variation 41.65
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
415.0 day*μg/mL
Geometric Coefficient of Variation 52.77
449.3 day*μg/mL
Geometric Coefficient of Variation 42.12

SECONDARY outcome

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

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.

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.

Outcome measures

Outcome measures
Measure
Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material)
n=69 Participants
Participants received AZD7442 as a single intramuscular (IM) dose (co-formulation of AZD8895 + AZD1061) (clonal cell line material) on Day 1.
Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material)
n=66 Participants
Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (clonal cell line material) on Day 1.
Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material)
n=66 Participants
Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (cell pool material) on Day 1.
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
1752 day*μg/mL
Geometric Coefficient of Variation 38.42
1757 day*μg/mL
Geometric Coefficient of Variation 33.67
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
918.9 day*μg/mL
Geometric Coefficient of Variation 35.90
886.9 day*μg/mL
Geometric Coefficient of Variation 33.87
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
826.0 day*μg/mL
Geometric Coefficient of Variation 43.98
865.8 day*μg/mL
Geometric Coefficient of Variation 35.33

SECONDARY outcome

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

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.

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.

Outcome measures

Outcome measures
Measure
Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material)
n=69 Participants
Participants received AZD7442 as a single intramuscular (IM) dose (co-formulation of AZD8895 + AZD1061) (clonal cell line material) on Day 1.
Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material)
n=66 Participants
Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (clonal cell line material) on Day 1.
Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material)
n=65 Participants
Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (cell pool material) on Day 1.
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 37.20
2453 day*μg/mL
Geometric Coefficient of Variation 36.03
2430 day*μg/mL
Geometric Coefficient of Variation 32.95
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
1283 day*μg/mL
Geometric Coefficient of Variation 33.67
1227 day*μg/mL
Geometric Coefficient of Variation 32.85
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
1161 day*μg/mL
Geometric Coefficient of Variation 41.27
1198 day*μg/mL
Geometric Coefficient of Variation 34.51

SECONDARY outcome

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

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.

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.

Outcome measures

Outcome measures
Measure
Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material)
n=65 Participants
Participants received AZD7442 as a single intramuscular (IM) dose (co-formulation of AZD8895 + AZD1061) (clonal cell line material) on Day 1.
Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material)
n=65 Participants
Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (clonal cell line material) on Day 1.
Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material)
n=63 Participants
Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (cell pool material) on Day 1.
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
3788 day*μg/mL
Geometric Coefficient of Variation 36.10
3655 day*μg/mL
Geometric Coefficient of Variation 36.41
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
1981 day*μg/mL
Geometric Coefficient of Variation 33.77
1856 day*μg/mL
Geometric Coefficient of Variation 36.27
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
1794 day*μg/mL
Geometric Coefficient of Variation 41.11
1793 day*μg/mL
Geometric Coefficient of Variation 37.62

SECONDARY outcome

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

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.

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.

Outcome measures

Outcome measures
Measure
Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material)
n=65 Participants
Participants received AZD7442 as a single intramuscular (IM) dose (co-formulation of AZD8895 + AZD1061) (clonal cell line material) on Day 1.
Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material)
n=65 Participants
Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (clonal cell line material) on Day 1.
Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material)
n=62 Participants
Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (cell pool material) on Day 1.
Time of Last Quantifiable Concentration (Tlast)
AZD7442
357.98 Day
Interval 85.01 to 382.06
358.02 Day
Interval 60.85 to 367.97
357.16 Day
Interval 90.98 to 366.23
Time of Last Quantifiable Concentration (Tlast)
AZD8895
357.98 Day
Interval 84.99 to 382.06
358.02 Day
Interval 60.85 to 367.97
357.05 Day
Interval 90.98 to 366.23
Time of Last Quantifiable Concentration (Tlast)
AZD1061
357.26 Day
Interval 85.01 to 369.96
357.98 Day
Interval 60.85 to 367.97
357.16 Day
Interval 90.98 to 366.23

SECONDARY outcome

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

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.

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.

Outcome measures

Outcome measures
Measure
Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material)
n=64 Participants
Participants received AZD7442 as a single intramuscular (IM) dose (co-formulation of AZD8895 + AZD1061) (clonal cell line material) on Day 1.
Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material)
n=65 Participants
Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (clonal cell line material) on Day 1.
Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material)
n=62 Participants
Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (cell pool material) on Day 1.
Terminal Half-life (t½λz)
AZD7442
75.13 Day
Geometric Coefficient of Variation 36.76
81.22 Day
Geometric Coefficient of Variation 29.11
76.52 Day
Geometric Coefficient of Variation 32.72
Terminal Half-life (t½λz)
AZD8895
77.77 Day
Geometric Coefficient of Variation 36.38
83.73 Day
Geometric Coefficient of Variation 30.12
79.19 Day
Geometric Coefficient of Variation 33.93
Terminal Half-life (t½λz)
AZD1061
74.11 Day
Geometric Coefficient of Variation 34.48
79.19 Day
Geometric Coefficient of Variation 27.68
73.71 Day
Geometric Coefficient of Variation 31.06

SECONDARY outcome

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

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.

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.

Outcome measures

Outcome measures
Measure
Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material)
n=63 Participants
Participants received AZD7442 as a single intramuscular (IM) dose (co-formulation of AZD8895 + AZD1061) (clonal cell line material) on Day 1.
Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material)
n=65 Participants
Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (clonal cell line material) on Day 1.
Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material)
n=62 Participants
Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (cell pool material) on Day 1.
Apparent Clearance After Extravascular Administration (CL/F)
AZD1061
0.06450 Liter per day (L/day)
Geometric Coefficient of Variation 42.69
0.06431 Liter per day (L/day)
Geometric Coefficient of Variation 43.42
0.06652 Liter per day (L/day)
Geometric Coefficient of Variation 41.70
Apparent Clearance After Extravascular Administration (CL/F)
AZD7442
0.06462 Liter per day (L/day)
Geometric Coefficient of Variation 43.12
0.06024 Liter per day (L/day)
Geometric Coefficient of Variation 38.96
0.06429 Liter per day (L/day)
Geometric Coefficient of Variation 41.06
Apparent Clearance After Extravascular Administration (CL/F)
AZD8895
0.06364 Liter per day (L/day)
Geometric Coefficient of Variation 42.72
0.05695 Liter per day (L/day)
Geometric Coefficient of Variation 37.13
0.06236 Liter per day (L/day)
Geometric Coefficient of Variation 41.42

SECONDARY outcome

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

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.

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.

Outcome measures

Outcome measures
Measure
Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material)
n=63 Participants
Participants received AZD7442 as a single intramuscular (IM) dose (co-formulation of AZD8895 + AZD1061) (clonal cell line material) on Day 1.
Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material)
n=65 Participants
Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (clonal cell line material) on Day 1.
Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material)
n=62 Participants
Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (cell pool material) on Day 1.
Volume of Distribution Based on Terminal Phase After Extravascular Administration (Vz/F)
AZD7442
6.960 Liter (L)
Geometric Coefficient of Variation 35.71
7.058 Liter (L)
Geometric Coefficient of Variation 32.17
7.098 Liter (L)
Geometric Coefficient of Variation 24.94
Volume of Distribution Based on Terminal Phase After Extravascular Administration (Vz/F)
AZD8895
7.129 Liter (L)
Geometric Coefficient of Variation 35.27
6.880 Liter (L)
Geometric Coefficient of Variation 30.92
7.125 Liter (L)
Geometric Coefficient of Variation 24.29
Volume of Distribution Based on Terminal Phase After Extravascular Administration (Vz/F)
AZD1061
6.852 Liter (L)
Geometric Coefficient of Variation 36.99
7.347 Liter (L)
Geometric Coefficient of Variation 37.76
7.075 Liter (L)
Geometric Coefficient of Variation 26.48

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material)
n=76 Participants
Participants received AZD7442 as a single intramuscular (IM) dose (co-formulation of AZD8895 + AZD1061) (clonal cell line material) on Day 1.
Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material)
n=72 Participants
Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (clonal cell line material) on Day 1.
Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material)
n=76 Participants
Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (cell pool material) on Day 1.
Number of Participants With Adverse Events (AEs)
Any AE
21 Participants
21 Participants
26 Participants
Number of Participants With Adverse Events (AEs)
Any SAE
2 Participants
0 Participants
1 Participants
Number of Participants With Adverse Events (AEs)
Any severe AE
1 Participants
0 Participants
0 Participants
Number of Participants With Adverse Events (AEs)
Any AESI
1 Participants
1 Participants
0 Participants
Number of Participants With Adverse Events (AEs)
Any SAE with outcome death
0 Participants
0 Participants
0 Participants
Number of Participants With Adverse Events (AEs)
Any AE leading to study discontinuation
0 Participants
0 Participants
0 Participants
Number of Participants With Adverse Events (AEs)
Any possibly related AE
3 Participants
1 Participants
1 Participants
Number of Participants With Adverse Events (AEs)
Any possibly related SAE
0 Participants
0 Participants
0 Participants
Number of Participants With Adverse Events (AEs)
Any possibly related severe AE
0 Participants
0 Participants
0 Participants
Number of Participants With Adverse Events (AEs)
Any possibly related AESI
1 Participants
1 Participants
0 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material)
n=73 Participants
Participants received AZD7442 as a single intramuscular (IM) dose (co-formulation of AZD8895 + AZD1061) (clonal cell line material) on Day 1.
Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material)
n=70 Participants
Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (clonal cell line material) on Day 1.
Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material)
n=71 Participants
Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (cell pool material) on Day 1.
Number of Participants With Positive Anti-AZD8895 and Anti-AZD1061 Antibodies
AZD8895
6 Participants
2 Participants
2 Participants
Number of Participants With Positive Anti-AZD8895 and Anti-AZD1061 Antibodies
AZD1061
7 Participants
2 Participants
1 Participants

Adverse Events

Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material)

Serious events: 2 serious events
Other events: 2 other events
Deaths: 0 deaths

Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material)

Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths

Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material)

Serious events: 1 serious events
Other events: 10 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material)
n=76 participants at risk
Participants received AZD7442 as a single intramuscular (IM) dose (co-formulation of AZD8895 + AZD1061) (clonal cell line material) on Day 1.
Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material)
n=72 participants at risk
Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (clonal cell line material) on Day 1.
Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material)
n=76 participants at risk
Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (cell pool material) on Day 1.
Psychiatric disorders
Major depression
1.3%
1/76 • From Day 1 until Follow-up visit (Day 361)
The safety analysis set included all participants who were randomized and received any amount of IMP.
0.00%
0/72 • From Day 1 until Follow-up visit (Day 361)
The safety analysis set included all participants who were randomized and received any amount of IMP.
0.00%
0/76 • From Day 1 until Follow-up visit (Day 361)
The safety analysis set included all participants who were randomized and received any amount of IMP.
Cardiac disorders
Angina pectoris
0.00%
0/76 • From Day 1 until Follow-up visit (Day 361)
The safety analysis set included all participants who were randomized and received any amount of IMP.
0.00%
0/72 • From Day 1 until Follow-up visit (Day 361)
The safety analysis set included all participants who were randomized and received any amount of IMP.
1.3%
1/76 • From Day 1 until Follow-up visit (Day 361)
The safety analysis set included all participants who were randomized and received any amount of IMP.
Cardiac disorders
Coronary artery occlusion
1.3%
1/76 • From Day 1 until Follow-up visit (Day 361)
The safety analysis set included all participants who were randomized and received any amount of IMP.
0.00%
0/72 • From Day 1 until Follow-up visit (Day 361)
The safety analysis set included all participants who were randomized and received any amount of IMP.
0.00%
0/76 • From Day 1 until Follow-up visit (Day 361)
The safety analysis set included all participants who were randomized and received any amount of IMP.

Other adverse events

Other adverse events
Measure
Treatment A: AZD8895 and AZD1061 (Coformulation, Clonal Cell Line Material)
n=76 participants at risk
Participants received AZD7442 as a single intramuscular (IM) dose (co-formulation of AZD8895 + AZD1061) (clonal cell line material) on Day 1.
Treatment B: AZD8895 and AZD1061 (Separate Vials, Clonal Cell Line Material)
n=72 participants at risk
Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (clonal cell line material) on Day 1.
Treatment C: AZD8895 and AZD1061 (Separate Vials, Cell Pool Material)
n=76 participants at risk
Participants received AZD7442 as two separate IM doses of the individual mAbs (AZD8895 and then AZD1061) (cell pool material) on Day 1.
Infections and infestations
COVID-19
2.6%
2/76 • Number of events 2 • From Day 1 until Follow-up visit (Day 361)
The safety analysis set included all participants who were randomized and received any amount of IMP.
11.1%
8/72 • Number of events 8 • From Day 1 until Follow-up visit (Day 361)
The safety analysis set included all participants who were randomized and received any amount of IMP.
13.2%
10/76 • Number of events 10 • From Day 1 until Follow-up visit (Day 361)
The safety analysis set included all participants who were randomized and received any amount of IMP.

Additional Information

Global Clinical Lead

AstraZeneca Clinical Study Information Center

Phone: 1-877-240-9479

Results disclosure agreements

  • Principal investigator is a sponsor employee No unpublished information contained herein may be disclosed without prior written approval from AstraZeneca AB. Access to this document must be restricted to relevant parties.
  • Publication restrictions are in place

Restriction type: OTHER