Trial Outcomes & Findings for Study of AZD1222 for the Prevention of COVID-19 in Japan (NCT NCT04568031)

NCT ID: NCT04568031

Last Updated: 2024-03-01

Results Overview

Seroresponse is a binary outcome where a success is when the fold rise in titers compared with baseline is \>= 4. The fold rise in titers was calculated as the ratio of the post-vaccination titer level to the baseline titer level. The percentage of participants with a post-vaccination seroresponse (\>= 4-fold rise in titers from Day 1 baseline value to Day 57) to the S antigen of AZD1222 as measured by MSD serology assay is reported.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

256 participants

Primary outcome timeframe

Baseline (Day 1) and Day 57

Results posted on

2024-03-01

Participant Flow

This Phase I/II study was conducted in healthy, severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) naïve participants at 5 study centers in Japan. First participant was randomized on 23 August 2020 and final data cut-off (DCO) date was 17 January 2022.

The study had a screening period (14 days), followed by vaccination and follow-up period (up to 365 days). The study consists of 2 cohorts (Cohort C and Cohort D) with different age populations. The Cohort C included participants aged 18 to 55 years and Cohort D included participants aged \>= 56 years. A total of 256 participants were randomized in a 3:1 ratio to receive AZD1222 or placebo.

Participant milestones

Participant milestones
Measure
Cohort C: AZD1222
Participants were randomized to receive 2 intramuscular (IM) doses of either 5\*10\^10 viral particles (vp) (nominal, ± 1.5\*10\^10 vp) AZD1222 on Days 1 and 29.
Cohort C: Placebo
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Cohort D: AZD1222
Participants were randomized to receive 2 IM doses of either 5\*10\^10 vp (nominal, ± 1.5\*10\^10 vp) AZD1222 on Days 1 and 29.
Cohort D: Placebo
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Overall Study
STARTED
96
32
96
32
Overall Study
Participants Received 1 Vaccination
96
32
96
32
Overall Study
Participants Received 2 Vaccinations
84
30
92
31
Overall Study
COMPLETED
93
32
91
31
Overall Study
NOT COMPLETED
3
0
5
1

Reasons for withdrawal

Reasons for withdrawal
Measure
Cohort C: AZD1222
Participants were randomized to receive 2 intramuscular (IM) doses of either 5\*10\^10 viral particles (vp) (nominal, ± 1.5\*10\^10 vp) AZD1222 on Days 1 and 29.
Cohort C: Placebo
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Cohort D: AZD1222
Participants were randomized to receive 2 IM doses of either 5\*10\^10 vp (nominal, ± 1.5\*10\^10 vp) AZD1222 on Days 1 and 29.
Cohort D: Placebo
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Overall Study
Lost to Follow-up
1
0
0
0
Overall Study
Physician Decision
1
0
1
0
Overall Study
Withdrawal by Subject
1
0
4
1

Baseline Characteristics

Study of AZD1222 for the Prevention of COVID-19 in Japan

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Cohort C: AZD1222
n=96 Participants
Participants were randomized to receive 2 IM doses of either 5\*10\^10 vp (nominal, ± 1.5\*10\^10 vp) AZD1222 on Days 1 and 29.
Cohort C: Placebo
n=32 Participants
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Cohort D: AZD1222
n=96 Participants
Participants were randomized to receive 2 IM doses of either 5\*10\^10 vp (nominal, ± 1.5\*10\^10 vp) AZD1222 on Days 1 and 29.
Cohort D: Placebo
n=32 Participants
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Total
n=256 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
Age, Categorical
Between 18 and 65 years
96 Participants
n=5 Participants
32 Participants
n=7 Participants
51 Participants
n=5 Participants
14 Participants
n=4 Participants
193 Participants
n=21 Participants
Age, Categorical
>=65 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
45 Participants
n=5 Participants
18 Participants
n=4 Participants
63 Participants
n=21 Participants
Sex: Female, Male
Female
25 Participants
n=5 Participants
8 Participants
n=7 Participants
40 Participants
n=5 Participants
14 Participants
n=4 Participants
87 Participants
n=21 Participants
Sex: Female, Male
Male
71 Participants
n=5 Participants
24 Participants
n=7 Participants
56 Participants
n=5 Participants
18 Participants
n=4 Participants
169 Participants
n=21 Participants
Race/Ethnicity, Customized
Asian
96 Participants
n=5 Participants
32 Participants
n=7 Participants
96 Participants
n=5 Participants
32 Participants
n=4 Participants
256 Participants
n=21 Participants
Race/Ethnicity, Customized
Hispanic or Latino
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
Race/Ethnicity, Customized
Not Hispanic or Latino
96 Participants
n=5 Participants
32 Participants
n=7 Participants
96 Participants
n=5 Participants
32 Participants
n=4 Participants
256 Participants
n=21 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) and Day 57

Population: The Fully vaccinated analysis set (FVS) for immunogenicity included all participants in the TVS who received 2 study vaccinations and had no important protocol deviations judged to have the potential to interfere with the generation or interpretation of immune responses. Only participants evaluated for seroresponse at Day 57 are reported. Participants with seroresponse to nucleocapsid antibodies by MSD serology assay at post-baseline up to Day 57 were excluded from this analysis set.

Seroresponse is a binary outcome where a success is when the fold rise in titers compared with baseline is \>= 4. The fold rise in titers was calculated as the ratio of the post-vaccination titer level to the baseline titer level. The percentage of participants with a post-vaccination seroresponse (\>= 4-fold rise in titers from Day 1 baseline value to Day 57) to the S antigen of AZD1222 as measured by MSD serology assay is reported.

Outcome measures

Outcome measures
Measure
Cohort C: AZD1222
n=83 Participants
Participants were randomized to receive 2 IM doses of either 5\*10\^10 vp (nominal, ± 1.5\*10\^10 vp) AZD1222 on Days 1 and 29.
Cohort C: Placebo
n=29 Participants
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Cohort D: AZD1222
n=91 Participants
Participants were randomized to receive 2 IM doses of either 5\*10\^10 vp (nominal, ± 1.5\*10\^10 vp) AZD1222 on Days 1 and 29.
Cohort D: Placebo
n=31 Participants
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Percentage of Participants With Seroresponse to the Spike (S) Antigen of AZD1222 as Measured by Meso Scale Discovery (MSD) Serology Assay
100.0 percentage of participants
0.0 percentage of participants
100.0 percentage of participants
0.0 percentage of participants

PRIMARY outcome

Timeframe: From Day 1 up to 7 days post each dose of study vaccination, approximately 14 days

Population: The TVS included all participants who received at least 1 dose of study vaccination.

Solicited AEs are local or systemic predefined AEs for reactogenicity assessment. Participants were given an axillary thermometer, tape measure, and access to app for the solicited AE eDiary, with instructions on use, along with the emergency 24-hour telephone number to contact the on-call study physician if needed. Participants were instructed to record for 7 days following administration of each dose of AZD1222, the timing and severity of local and systemic solicited AEs, if applicable, and whether medication was taken to relieve the symptoms.

Outcome measures

Outcome measures
Measure
Cohort C: AZD1222
n=96 Participants
Participants were randomized to receive 2 IM doses of either 5\*10\^10 vp (nominal, ± 1.5\*10\^10 vp) AZD1222 on Days 1 and 29.
Cohort C: Placebo
n=32 Participants
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Cohort D: AZD1222
n=96 Participants
Participants were randomized to receive 2 IM doses of either 5\*10\^10 vp (nominal, ± 1.5\*10\^10 vp) AZD1222 on Days 1 and 29.
Cohort D: Placebo
n=32 Participants
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Number of Participants With Local Solicited Adverse Events (AE)
After first vaccination
70 Participants
4 Participants
46 Participants
2 Participants
Number of Participants With Local Solicited Adverse Events (AE)
After second vaccination
37 Participants
3 Participants
36 Participants
0 Participants
Number of Participants With Local Solicited Adverse Events (AE)
After any vaccination
74 Participants
5 Participants
53 Participants
2 Participants

PRIMARY outcome

Timeframe: From Day 1 up to 7 days post each dose of study vaccination, approximately 14 days

Population: The TVS included all participants who received at least 1 dose of study vaccination.

Solicited AEs are local or systemic predefined AEs for reactogenicity assessment. Participants were given an axillary thermometer, tape measure, and access to app for the solicited AE eDiary, with instructions on use, along with the emergency 24-hour telephone number to contact the on-call study physician if needed. Participants were instructed to record for 7 days following administration of each dose of AZD1222, the timing and severity of local and systemic solicited AEs, if applicable, and whether medication was taken to relieve the symptoms.

Outcome measures

Outcome measures
Measure
Cohort C: AZD1222
n=96 Participants
Participants were randomized to receive 2 IM doses of either 5\*10\^10 vp (nominal, ± 1.5\*10\^10 vp) AZD1222 on Days 1 and 29.
Cohort C: Placebo
n=32 Participants
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Cohort D: AZD1222
n=96 Participants
Participants were randomized to receive 2 IM doses of either 5\*10\^10 vp (nominal, ± 1.5\*10\^10 vp) AZD1222 on Days 1 and 29.
Cohort D: Placebo
n=32 Participants
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Number of Participants With Systemic Solicited AEs
After first vaccination
65 Participants
6 Participants
41 Participants
3 Participants
Number of Participants With Systemic Solicited AEs
After second vaccination
30 Participants
7 Participants
24 Participants
3 Participants
Number of Participants With Systemic Solicited AEs
After any vaccination
68 Participants
11 Participants
47 Participants
5 Participants

PRIMARY outcome

Timeframe: From Day 1 up to 28 days post each dose of study vaccination, approximately 57 days

Population: The TVS included all participants who received at least 1 dose of study vaccination. Unsolicited AEs that started after the inoculation of non-study coronavirus disease 2019 vaccine were not included in this analysis.

An AE is the development of any untoward medical occurrence in a clinical study participant administered medicinal product and which does not necessarily have a causal relationship with this medicinal product. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is an AE occurring during any study phase that fulfils one or more of the following criteria: death; immediately life-threatening; in-participant hospitalization or prolongation of existing hospitalization; persistent or significant disability or incapacity; congenital abnormality or birth defect; an important medical event. The AESIs were events of scientific and medical interest specific to the further understanding of the study vaccination safety profile and required close monitoring and rapid communication by the investigators to the sponsor.

Outcome measures

Outcome measures
Measure
Cohort C: AZD1222
n=96 Participants
Participants were randomized to receive 2 IM doses of either 5\*10\^10 vp (nominal, ± 1.5\*10\^10 vp) AZD1222 on Days 1 and 29.
Cohort C: Placebo
n=32 Participants
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Cohort D: AZD1222
n=96 Participants
Participants were randomized to receive 2 IM doses of either 5\*10\^10 vp (nominal, ± 1.5\*10\^10 vp) AZD1222 on Days 1 and 29.
Cohort D: Placebo
n=32 Participants
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Number of Participants With AEs, Serious AEs (SAE) and Adverse Event of Special Interest (AESI) Occurring Post Each Dose of Study Vaccination
AEs
28 Participants
4 Participants
22 Participants
9 Participants
Number of Participants With AEs, Serious AEs (SAE) and Adverse Event of Special Interest (AESI) Occurring Post Each Dose of Study Vaccination
SAEs
0 Participants
1 Participants
3 Participants
1 Participants
Number of Participants With AEs, Serious AEs (SAE) and Adverse Event of Special Interest (AESI) Occurring Post Each Dose of Study Vaccination
AESIs
0 Participants
0 Participants
0 Participants
0 Participants

PRIMARY outcome

Timeframe: From Day 1 up to 28 days post each dose of study vaccination, approximately 57 days

Population: The TVS included all participants who received at least 1 dose of study vaccination.

Clinical laboratory values were evaluated for each laboratory parameter as applicable including hematology and clinical chemistry. The baseline was defined as the last non-missing measurement taken prior to the first dose of study vaccination (including unscheduled measurements, if any).

Outcome measures

Outcome measures
Measure
Cohort C: AZD1222
n=96 Participants
Participants were randomized to receive 2 IM doses of either 5\*10\^10 vp (nominal, ± 1.5\*10\^10 vp) AZD1222 on Days 1 and 29.
Cohort C: Placebo
n=32 Participants
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Cohort D: AZD1222
n=96 Participants
Participants were randomized to receive 2 IM doses of either 5\*10\^10 vp (nominal, ± 1.5\*10\^10 vp) AZD1222 on Days 1 and 29.
Cohort D: Placebo
n=32 Participants
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Parameters
0 Participants
0 Participants
0 Participants
0 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) and Day 57

Population: The FVS for immunogenicity included all participants in the TVS who received 2 study vaccinations and had no important protocol deviations judged to have the potential to interfere with the generation or interpretation of immune responses. Only participants evaluated for seroresponse at Day 57 are reported. Participants with seroresponse to nucleocapsid antibodies by MSD serology assay at post-baseline up to Day 57 were excluded from this analysis set.

Seroresponse is a binary outcome where a success is when the fold rise in titers compared with baseline is \>= 4. The fold rise in titers was calculated as the ratio of the post-vaccination titer level to the baseline titer level. The percentage of participants with a post-vaccination seroresponse (\>= 4-fold rise in titers from Day 1 baseline value to Day 57) to the RBD antigen of AZD1222 as measured by MSD serology assay is reported.

Outcome measures

Outcome measures
Measure
Cohort C: AZD1222
n=83 Participants
Participants were randomized to receive 2 IM doses of either 5\*10\^10 vp (nominal, ± 1.5\*10\^10 vp) AZD1222 on Days 1 and 29.
Cohort C: Placebo
n=29 Participants
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Cohort D: AZD1222
n=91 Participants
Participants were randomized to receive 2 IM doses of either 5\*10\^10 vp (nominal, ± 1.5\*10\^10 vp) AZD1222 on Days 1 and 29.
Cohort D: Placebo
n=31 Participants
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Percentage of Participants With Seroresponse to the Receptor-Binding Domain (RBD) Antigen of AZD1222 as Measured by MSD Serology Assay
100.0 percentage of participants
0.0 percentage of participants
100.0 percentage of participants
0.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day 1) and Days 15, 29, 43, 57, 183, and 365

Population: The FVS for immunogenicity included all participants in the TVS who received 2 study vaccinations and had no important protocol deviations judged to have the potential to interfere with the generation or interpretation of immune responses. Participants with seroresponse to nucleocapsid antibodies by MSD serology assay at post-baseline up to Day 57 were excluded from this analysis set.

The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titer/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titer, where 'n' is the number of participants with titer information.

Outcome measures

Outcome measures
Measure
Cohort C: AZD1222
n=83 Participants
Participants were randomized to receive 2 IM doses of either 5\*10\^10 vp (nominal, ± 1.5\*10\^10 vp) AZD1222 on Days 1 and 29.
Cohort C: Placebo
n=29 Participants
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Cohort D: AZD1222
n=91 Participants
Participants were randomized to receive 2 IM doses of either 5\*10\^10 vp (nominal, ± 1.5\*10\^10 vp) AZD1222 on Days 1 and 29.
Cohort D: Placebo
n=31 Participants
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Geometric Mean Titers (GMTs) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay
RBD Antibody Titer: Day 57
16775.12 arbitrary units per milliliter (AU/mL)
Interval 13921.806 to 20213.221
114.54 arbitrary units per milliliter (AU/mL)
Interval 97.063 to 135.156
14094.42 arbitrary units per milliliter (AU/mL)
Interval 11437.864 to 17367.992
116.24 arbitrary units per milliliter (AU/mL)
Interval 96.03 to 140.713
Geometric Mean Titers (GMTs) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay
S Antibody Titer: Baseline (Day 1)
62.18 arbitrary units per milliliter (AU/mL)
Interval 48.136 to 80.31
46.00 arbitrary units per milliliter (AU/mL)
Interval 32.713 to 64.672
39.06 arbitrary units per milliliter (AU/mL)
Interval 31.824 to 47.931
39.87 arbitrary units per milliliter (AU/mL)
Interval 24.214 to 65.662
Geometric Mean Titers (GMTs) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay
S Antibody Titer: Day 15
2520.37 arbitrary units per milliliter (AU/mL)
Interval 1868.317 to 3399.988
43.70 arbitrary units per milliliter (AU/mL)
Interval 31.6 to 60.426
999.28 arbitrary units per milliliter (AU/mL)
Interval 751.737 to 1328.342
39.24 arbitrary units per milliliter (AU/mL)
Interval 24.016 to 64.105
Geometric Mean Titers (GMTs) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay
S Antibody Titer: Day 29
7971.03 arbitrary units per milliliter (AU/mL)
Interval 6278.011 to 10120.625
42.66 arbitrary units per milliliter (AU/mL)
Interval 30.843 to 58.993
6720.46 arbitrary units per milliliter (AU/mL)
Interval 5361.399 to 8424.022
40.03 arbitrary units per milliliter (AU/mL)
Interval 24.956 to 64.223
Geometric Mean Titers (GMTs) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay
S Antibody Titer: Day 43
17708.74 arbitrary units per milliliter (AU/mL)
Interval 14671.831 to 21374.262
41.61 arbitrary units per milliliter (AU/mL)
Interval 29.411 to 58.879
15594.37 arbitrary units per milliliter (AU/mL)
Interval 12792.879 to 19009.367
37.89 arbitrary units per milliliter (AU/mL)
Interval 23.025 to 62.344
Geometric Mean Titers (GMTs) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay
S Antibody Titer: Day 57
14986.27 arbitrary units per milliliter (AU/mL)
Interval 12455.149 to 18031.758
44.24 arbitrary units per milliliter (AU/mL)
Interval 31.816 to 61.507
12824.27 arbitrary units per milliliter (AU/mL)
Interval 10516.28 to 15638.797
38.75 arbitrary units per milliliter (AU/mL)
Interval 23.604 to 63.618
Geometric Mean Titers (GMTs) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay
S Antibody Titer: Day 183
4454.01 arbitrary units per milliliter (AU/mL)
Interval 3503.969 to 5661.645
53.28 arbitrary units per milliliter (AU/mL)
Interval 36.416 to 77.945
3424.65 arbitrary units per milliliter (AU/mL)
Interval 2758.191 to 4252.152
45.89 arbitrary units per milliliter (AU/mL)
Interval 28.326 to 74.347
Geometric Mean Titers (GMTs) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay
S Antibody Titer: Day 365
3691.12 arbitrary units per milliliter (AU/mL)
Interval 2468.353 to 5519.626
760.64 arbitrary units per milliliter (AU/mL)
Interval 0.002 to 266254529.058
2691.98 arbitrary units per milliliter (AU/mL)
Interval 1910.675 to 3792.785
116.38 arbitrary units per milliliter (AU/mL)
Interval 0.611 to 22179.458
Geometric Mean Titers (GMTs) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay
RBD Antibody Titer: Baseline (Day 1)
122.62 arbitrary units per milliliter (AU/mL)
Interval 106.105 to 141.715
114.89 arbitrary units per milliliter (AU/mL)
Interval 96.952 to 136.148
105.41 arbitrary units per milliliter (AU/mL)
Interval 100.326 to 110.752
119.83 arbitrary units per milliliter (AU/mL)
Interval 97.625 to 147.077
Geometric Mean Titers (GMTs) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay
RBD Antibody Titer: Day 15
945.33 arbitrary units per milliliter (AU/mL)
Interval 678.34 to 1317.392
116.04 arbitrary units per milliliter (AU/mL)
Interval 96.504 to 139.521
430.65 arbitrary units per milliliter (AU/mL)
Interval 329.174 to 563.418
118.91 arbitrary units per milliliter (AU/mL)
Interval 97.844 to 144.52
Geometric Mean Titers (GMTs) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay
RBD Antibody Titer: Day 29
6466.23 arbitrary units per milliliter (AU/mL)
Interval 5026.53 to 8318.284
115.39 arbitrary units per milliliter (AU/mL)
Interval 96.817 to 137.518
5616.00 arbitrary units per milliliter (AU/mL)
Interval 4468.764 to 7057.759
116.63 arbitrary units per milliliter (AU/mL)
Interval 94.796 to 143.491
Geometric Mean Titers (GMTs) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay
RBD Antibody Titer: Day 43
20719.36 arbitrary units per milliliter (AU/mL)
Interval 17079.781 to 25134.511
114.43 arbitrary units per milliliter (AU/mL)
Interval 97.164 to 134.766
17677.04 arbitrary units per milliliter (AU/mL)
Interval 14383.279 to 21725.058
123.20 arbitrary units per milliliter (AU/mL)
Interval 100.706 to 150.715
Geometric Mean Titers (GMTs) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay
RBD Antibody Titer: Day 183
4245.22 arbitrary units per milliliter (AU/mL)
Interval 3309.128 to 5446.106
111.24 arbitrary units per milliliter (AU/mL)
Interval 98.273 to 125.916
3354.78 arbitrary units per milliliter (AU/mL)
Interval 2646.741 to 4252.239
127.71 arbitrary units per milliliter (AU/mL)
Interval 95.347 to 171.052
Geometric Mean Titers (GMTs) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay
RBD Antibody Titer: Day 365
3550.69 arbitrary units per milliliter (AU/mL)
Interval 2296.498 to 5489.828
1520.17 arbitrary units per milliliter (AU/mL)
Interval 0.014 to 169886733.576
2643.76 arbitrary units per milliliter (AU/mL)
Interval 1811.827 to 3857.686
304.93 arbitrary units per milliliter (AU/mL)
Interval 9.346 to 9948.763

SECONDARY outcome

Timeframe: Baseline (Day 1) and Days 15, 29, 43, 57, 183, and 365

Population: The FVS for immunogenicity included all participants in the TVS who received 2 study vaccinations and had no important protocol deviations judged to have the potential to interfere with the generation or interpretation of immune responses. Participants with seroresponse to nucleocapsid antibodies by MSD serology assay at post-baseline up to Day 57 were excluded from this analysis set.

The fold rise was calculated as the ratio of the post-vaccination titer level to the baseline titer level, where baseline was defined as the last measurement taken before the first dose of study vaccination. The GMFR was calculated as anti-logarithm of Σ (log base 2 transformed (post-vaccination titer/ pre-vaccination titer)/n). Where 'n' is the number of participants with titer information.

Outcome measures

Outcome measures
Measure
Cohort C: AZD1222
n=83 Participants
Participants were randomized to receive 2 IM doses of either 5\*10\^10 vp (nominal, ± 1.5\*10\^10 vp) AZD1222 on Days 1 and 29.
Cohort C: Placebo
n=29 Participants
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Cohort D: AZD1222
n=91 Participants
Participants were randomized to receive 2 IM doses of either 5\*10\^10 vp (nominal, ± 1.5\*10\^10 vp) AZD1222 on Days 1 and 29.
Cohort D: Placebo
n=31 Participants
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay
S Antibody Titer: Day 15
40.54 ratio
Interval 30.451 to 53.962
0.95 ratio
Interval 0.863 to 1.046
25.59 ratio
Interval 18.465 to 35.453
0.98 ratio
Interval 0.865 to 1.119
Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay
S Antibody Titer: Day 29
128.20 ratio
Interval 97.728 to 168.179
0.93 ratio
Interval 0.841 to 1.023
172.07 ratio
Interval 128.206 to 230.951
1.00 ratio
Interval 0.869 to 1.161
Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay
S Antibody Titer: Day 43
284.82 ratio
Interval 217.685 to 372.656
0.90 ratio
Interval 0.814 to 1.006
399.28 ratio
Interval 295.2 to 540.068
0.95 ratio
Interval 0.842 to 1.072
Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay
S Antibody Titer: Day 57
241.03 ratio
Interval 183.977 to 315.781
0.96 ratio
Interval 0.881 to 1.05
328.36 ratio
Interval 243.794 to 442.254
0.97 ratio
Interval 0.858 to 1.1
Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay
S Antibody Titer: Day 183
70.49 ratio
Interval 51.13 to 97.171
1.11 ratio
Interval 0.92 to 1.344
88.17 ratio
Interval 65.621 to 118.464
1.15 ratio
Interval 1.021 to 1.298
Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay
S Antibody Titer: Day 365
59.15 ratio
Interval 37.619 to 93.012
25.12 ratio
Interval 0.0 to 26524735.936
70.56 ratio
Interval 47.647 to 104.486
4.18 ratio
Interval 0.042 to 416.314
Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay
RBD Antibody Titer: Day 15
7.71 ratio
Interval 5.69 to 10.445
1.01 ratio
Interval 0.995 to 1.025
4.09 ratio
Interval 3.14 to 5.315
0.99 ratio
Interval 0.972 to 1.013
Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay
RBD Antibody Titer: Day 29
52.73 ratio
Interval 40.85 to 68.07
1.00 ratio
Interval 0.985 to 1.024
53.28 ratio
Interval 42.74 to 66.413
0.97 ratio
Interval 0.915 to 1.035
Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay
RBD Antibody Titer: Day 43
168.97 ratio
Interval 134.602 to 212.105
1.00 ratio
Interval 0.983 to 1.009
167.70 ratio
Interval 137.013 to 205.253
1.03 ratio
Interval 0.966 to 1.095
Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay
RBD Antibody Titer: Day 57
136.80 ratio
Interval 109.05 to 171.614
1.00 ratio
Interval 0.992 to 1.002
133.71 ratio
Interval 108.961 to 164.08
0.97 ratio
Interval 0.911 to 1.033
Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay
RBD Antibody Titer: Day 183
34.54 ratio
Interval 26.04 to 45.82
0.96 ratio
Interval 0.891 to 1.023
31.81 ratio
Interval 25.259 to 40.071
1.07 ratio
Interval 0.888 to 1.279
Geometric Mean Fold Rise (GMFR) for SARS-CoV-2 S and RBD Antibodies as Measured by MSD Serology Assay
RBD Antibody Titer: Day 365
28.76 ratio
Interval 18.123 to 45.629
14.90 ratio
Interval 0.0 to 1665556.212
25.03 ratio
Interval 17.383 to 36.049
2.99 ratio
Interval 0.092 to 97.537

SECONDARY outcome

Timeframe: Baseline (Day 1) and Day 57

Population: The FVS for immunogenicity included all participants in the TVS who received 2 study vaccinations and had no important protocol deviations judged to have the potential to interfere with the generation or interpretation of immune responses. Only participants evaluated for seroresponse at Day 57 are reported. Participants with seroresponse to nucleocapsid antibodies by MSD serology assay at post-baseline up to Day 57 were excluded from this analysis set.

Seroresponse is a binary outcome where a success is when the fold rise in titers compared with baseline is \>= 4. The fold rise in titers was calculated as the ratio of the post-vaccination titer level to the baseline titer level. The percentage of participants with a post-vaccination seroresponse (\>= 4-fold rise in titers from Day 1 baseline value to Day 57) to SARS-CoV-2 nAb of AZD1222 as measured by pseudo-neutralization assay is reported.

Outcome measures

Outcome measures
Measure
Cohort C: AZD1222
n=80 Participants
Participants were randomized to receive 2 IM doses of either 5\*10\^10 vp (nominal, ± 1.5\*10\^10 vp) AZD1222 on Days 1 and 29.
Cohort C: Placebo
n=29 Participants
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Cohort D: AZD1222
n=86 Participants
Participants were randomized to receive 2 IM doses of either 5\*10\^10 vp (nominal, ± 1.5\*10\^10 vp) AZD1222 on Days 1 and 29.
Cohort D: Placebo
n=30 Participants
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Percentage of Participants With Seroresponse to SARS-CoV-2 Neutralizing Antibodies (nAb) of AZD1222 as Measured by Pseudo-Neutralization Assay
67.5 percentage of participants
0.0 percentage of participants
57.0 percentage of participants
0.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day 1) and Days 29, 57, 183, and 365

Population: The FVS for immunogenicity included all participants in the TVS who received 2 study vaccinations and had no important protocol deviations judged to have the potential to interfere with the generation or interpretation of immune responses. Participants with seroresponse to nucleocapsid antibodies by MSD serology assay at post-baseline up to Day 57 were excluded from this analysis set.

The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titer/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titer, where 'n' is the number of participants with titer information.

Outcome measures

Outcome measures
Measure
Cohort C: AZD1222
n=83 Participants
Participants were randomized to receive 2 IM doses of either 5\*10\^10 vp (nominal, ± 1.5\*10\^10 vp) AZD1222 on Days 1 and 29.
Cohort C: Placebo
n=29 Participants
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Cohort D: AZD1222
n=91 Participants
Participants were randomized to receive 2 IM doses of either 5\*10\^10 vp (nominal, ± 1.5\*10\^10 vp) AZD1222 on Days 1 and 29.
Cohort D: Placebo
n=31 Participants
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
GMTs for SARS-CoV-2 nAb as Measured by Pseudo-Neutralization Assay
Baseline (Day 1)
20.84 AU/mL
Interval 19.206 to 22.604
20.00 AU/mL
Lower and upper limit of confidence interval was not evaluable due to below the level of detection. A titer value measured below the lower limit of quantification (LLOQ) was imputed to a value that is half of the LLOQ in summaries and analyses. The value of LLOQ is 40 AU/mL and upper limit of quantification (ULOQ) is 787339 AU/mL.
20.00 AU/mL
Lower and upper limit of confidence interval was not evaluable due to below the level of detection. A titer value measured below the LLOQ was imputed to a value that is half of the LLOQ in summaries and analyses. The value of LLOQ is 40 AU/mL and ULOQ is 787339 AU/mL.
20.82 AU/mL
Interval 19.175 to 22.616
GMTs for SARS-CoV-2 nAb as Measured by Pseudo-Neutralization Assay
Day 365
43.16 AU/mL
Interval 28.917 to 64.428
97.03 AU/mL
Interval 0.109 to 86708.084
32.44 AU/mL
Interval 24.376 to 43.159
25.40 AU/mL
Interval 11.875 to 54.316
GMTs for SARS-CoV-2 nAb as Measured by Pseudo-Neutralization Assay
Day 29
67.26 AU/mL
Interval 50.689 to 89.249
20.00 AU/mL
Lower and upper limit of confidence interval was not evaluable due to below the level of detection. A titer value measured below the LLOQ was imputed to a value that is half of the LLOQ in summaries and analyses. The value of LLOQ is 40 AU/mL and ULOQ is 787339 AU/mL.
46.11 AU/mL
Interval 36.577 to 58.132
21.07 AU/mL
Interval 18.947 to 23.422
GMTs for SARS-CoV-2 nAb as Measured by Pseudo-Neutralization Assay
Day 57
107.30 AU/mL
Interval 84.198 to 136.741
20.00 AU/mL
Lower and upper limit of confidence interval was not evaluable due to below the level of detection. A titer value measured below the LLOQ was imputed to a value that is half of the LLOQ in summaries and analyses. The value of LLOQ is 40 AU/mL and ULOQ is 787339 AU/mL.
90.00 AU/mL
Interval 70.051 to 115.618
20.00 AU/mL
Lower and upper limit of confidence interval was not evaluable due to below the level of detection. A titer value measured below the LLOQ was imputed to a value that is half of the LLOQ in summaries and analyses. The value of LLOQ is 40 AU/mL and ULOQ is 787339 AU/mL.
GMTs for SARS-CoV-2 nAb as Measured by Pseudo-Neutralization Assay
Day 183
31.14 AU/mL
Interval 24.679 to 39.281
20.00 AU/mL
Lower and upper limit of confidence interval was not evaluable due to below the level of detection. A titer value measured below the LLOQ was imputed to a value that is half of the LLOQ in summaries and analyses. The value of LLOQ is 40 AU/mL and ULOQ is 787339 AU/mL.
28.91 AU/mL
Interval 24.717 to 33.81
20.54 AU/mL
Interval 19.448 to 21.703

SECONDARY outcome

Timeframe: Baseline (Day 1) and Days 29, 57, 183, and 365

Population: The FVS for immunogenicity included all participants in the TVS who received 2 study vaccinations and had no important protocol deviations judged to have the potential to interfere with the generation or interpretation of immune responses. Participants with seroresponse to nucleocapsid antibodies by MSD serology assay at post-baseline up to Day 57 were excluded from this analysis set.

The fold rise was calculated as the ratio of the post-vaccination titer level to the baseline titer level, where baseline was defined as the last measurement taken before the first dose of study vaccination. The GMFR was calculated as anti-logarithm of Σ (log base 2 transformed (post-vaccination titer/ pre-vaccination titer)/n). Where 'n' is the number of participants with titer information.

Outcome measures

Outcome measures
Measure
Cohort C: AZD1222
n=81 Participants
Participants were randomized to receive 2 IM doses of either 5\*10\^10 vp (nominal, ± 1.5\*10\^10 vp) AZD1222 on Days 1 and 29.
Cohort C: Placebo
n=29 Participants
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Cohort D: AZD1222
n=88 Participants
Participants were randomized to receive 2 IM doses of either 5\*10\^10 vp (nominal, ± 1.5\*10\^10 vp) AZD1222 on Days 1 and 29.
Cohort D: Placebo
n=31 Participants
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
GMFR for SARS-CoV-2 nAb as Measured by Pseudo-Neutralization Assay
Day 29
3.21 ratio
Interval 2.469 to 4.184
1.00 ratio
Lower and upper limit of confidence interval was not evaluable due to below the level of detection. A titer value measured below the LLOQ was imputed to a value that is half of the LLOQ in summaries and analyses. The value of LLOQ is 40 AU/mL and ULOQ is 787339 AU/mL.
2.31 ratio
Interval 1.829 to 2.907
1.01 ratio
Interval 0.988 to 1.036
GMFR for SARS-CoV-2 nAb as Measured by Pseudo-Neutralization Assay
Day 57
5.14 ratio
Interval 4.066 to 6.503
1.00 ratio
Lower and upper limit of confidence interval was not evaluable due to below the level of detection. A titer value measured below the LLOQ was imputed to a value that is half of the LLOQ in summaries and analyses. The value of LLOQ is 40 AU/mL and ULOQ is 787339 AU/mL.
4.50 ratio
Interval 3.503 to 5.781
1.00 ratio
Lower and upper limit of confidence interval was not evaluable due to below the level of detection. A titer value measured below the LLOQ was imputed to a value that is half of the LLOQ in summaries and analyses. The value of LLOQ is 40 AU/mL and ULOQ is 787339 AU/mL.
GMFR for SARS-CoV-2 nAb as Measured by Pseudo-Neutralization Assay
Day 183
1.49 ratio
Interval 1.186 to 1.879
1.00 ratio
Lower and upper limit of confidence interval was not evaluable due to below the level of detection. A titer value measured below the LLOQ was imputed to a value that is half of the LLOQ in summaries and analyses. The value of LLOQ is 40 AU/mL and ULOQ is 787339 AU/mL.
1.45 ratio
Interval 1.236 to 1.69
0.99 ratio
Interval 0.96 to 1.014
GMFR for SARS-CoV-2 nAb as Measured by Pseudo-Neutralization Assay
Day 365
2.06 ratio
Interval 1.379 to 3.088
4.85 ratio
Interval 0.005 to 4335.404
1.62 ratio
Interval 1.219 to 2.158
1.27 ratio
Interval 0.594 to 2.716

SECONDARY outcome

Timeframe: From Day 1 up to final DCO of 17 January 2022, up to a maximum of 365 days

Population: The TVS included all participants who received at least 1 dose of study vaccination.

An SAE is an AE occurring during any study phase that fulfils one or more of the following criteria: death; immediately life-threatening; in-participant hospitalization or prolongation of existing hospitalization; persistent or significant disability or incapacity; congenital abnormality or birth defect; an important medical event. The AESIs were events of scientific and medical interest specific to the further understanding of the study vaccination safety profile and required close monitoring and rapid communication by the investigators to the sponsor.

Outcome measures

Outcome measures
Measure
Cohort C: AZD1222
n=96 Participants
Participants were randomized to receive 2 IM doses of either 5\*10\^10 vp (nominal, ± 1.5\*10\^10 vp) AZD1222 on Days 1 and 29.
Cohort C: Placebo
n=32 Participants
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Cohort D: AZD1222
n=96 Participants
Participants were randomized to receive 2 IM doses of either 5\*10\^10 vp (nominal, ± 1.5\*10\^10 vp) AZD1222 on Days 1 and 29.
Cohort D: Placebo
n=32 Participants
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Number of Participants With SAEs and AESIs Occurring Throughout the Study
AESIs
0 Participants
1 Participants
0 Participants
0 Participants
Number of Participants With SAEs and AESIs Occurring Throughout the Study
SAEs
0 Participants
2 Participants
3 Participants
1 Participants

Adverse Events

Cohorts C + D: AZD1222

Serious events: 3 serious events
Other events: 11 other events
Deaths: 0 deaths

Cohorts C + D: Placebo

Serious events: 3 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Cohorts C + D: AZD1222
n=192 participants at risk
Participants were randomized to receive 2 IM doses of either 5\*10\^10 vp (nominal, ± 1.5\*10\^10 vp) AZD1222 on Days 1 and 29.
Cohorts C + D: Placebo
n=64 participants at risk
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
Cardiac disorders
Sinus node dysfunction
0.00%
0/192 • AEs are reported from first administration of study vaccination up to final DCO of 17 January 2022, up to a maximum of 365 days
The TVS included all participants who received at least 1 dose of study vaccination.
1.6%
1/64 • Number of events 1 • AEs are reported from first administration of study vaccination up to final DCO of 17 January 2022, up to a maximum of 365 days
The TVS included all participants who received at least 1 dose of study vaccination.
Hepatobiliary disorders
Bile duct stone
0.52%
1/192 • Number of events 1 • AEs are reported from first administration of study vaccination up to final DCO of 17 January 2022, up to a maximum of 365 days
The TVS included all participants who received at least 1 dose of study vaccination.
0.00%
0/64 • AEs are reported from first administration of study vaccination up to final DCO of 17 January 2022, up to a maximum of 365 days
The TVS included all participants who received at least 1 dose of study vaccination.
Immune system disorders
Anaphylactic reaction
0.00%
0/192 • AEs are reported from first administration of study vaccination up to final DCO of 17 January 2022, up to a maximum of 365 days
The TVS included all participants who received at least 1 dose of study vaccination.
1.6%
1/64 • Number of events 1 • AEs are reported from first administration of study vaccination up to final DCO of 17 January 2022, up to a maximum of 365 days
The TVS included all participants who received at least 1 dose of study vaccination.
Infections and infestations
Pneumonia
0.52%
1/192 • Number of events 2 • AEs are reported from first administration of study vaccination up to final DCO of 17 January 2022, up to a maximum of 365 days
The TVS included all participants who received at least 1 dose of study vaccination.
0.00%
0/64 • AEs are reported from first administration of study vaccination up to final DCO of 17 January 2022, up to a maximum of 365 days
The TVS included all participants who received at least 1 dose of study vaccination.
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon adenoma
0.52%
1/192 • Number of events 1 • AEs are reported from first administration of study vaccination up to final DCO of 17 January 2022, up to a maximum of 365 days
The TVS included all participants who received at least 1 dose of study vaccination.
0.00%
0/64 • AEs are reported from first administration of study vaccination up to final DCO of 17 January 2022, up to a maximum of 365 days
The TVS included all participants who received at least 1 dose of study vaccination.
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Small intestine carcinoma
0.52%
1/192 • Number of events 1 • AEs are reported from first administration of study vaccination up to final DCO of 17 January 2022, up to a maximum of 365 days
The TVS included all participants who received at least 1 dose of study vaccination.
0.00%
0/64 • AEs are reported from first administration of study vaccination up to final DCO of 17 January 2022, up to a maximum of 365 days
The TVS included all participants who received at least 1 dose of study vaccination.
Nervous system disorders
Cerebral haemorrhage
0.52%
1/192 • Number of events 1 • AEs are reported from first administration of study vaccination up to final DCO of 17 January 2022, up to a maximum of 365 days
The TVS included all participants who received at least 1 dose of study vaccination.
0.00%
0/64 • AEs are reported from first administration of study vaccination up to final DCO of 17 January 2022, up to a maximum of 365 days
The TVS included all participants who received at least 1 dose of study vaccination.
Reproductive system and breast disorders
Cervical dysplasia
0.00%
0/192 • AEs are reported from first administration of study vaccination up to final DCO of 17 January 2022, up to a maximum of 365 days
The TVS included all participants who received at least 1 dose of study vaccination.
1.6%
1/64 • Number of events 1 • AEs are reported from first administration of study vaccination up to final DCO of 17 January 2022, up to a maximum of 365 days
The TVS included all participants who received at least 1 dose of study vaccination.

Other adverse events

Other adverse events
Measure
Cohorts C + D: AZD1222
n=192 participants at risk
Participants were randomized to receive 2 IM doses of either 5\*10\^10 vp (nominal, ± 1.5\*10\^10 vp) AZD1222 on Days 1 and 29.
Cohorts C + D: Placebo
n=64 participants at risk
Participants were randomized to receive 2 IM doses of placebo matching with AZD1222 on Days 1 and 29.
General disorders
Tenderness
5.7%
11/192 • Number of events 11 • AEs are reported from first administration of study vaccination up to final DCO of 17 January 2022, up to a maximum of 365 days
The TVS included all participants who received at least 1 dose of study vaccination.
0.00%
0/64 • AEs are reported from first administration of study vaccination up to final DCO of 17 January 2022, up to a maximum of 365 days
The TVS included all participants who received at least 1 dose of study vaccination.

Additional Information

Global Clinical Lead

AstraZeneca

Phone: 1-877-240-9479

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place