COVID-19, SARS-CoV-2
Conditions
Keywords
COVID-19 Vaccine
Brief summary
The aim of this study is to assess the immunogenicity and safety of AZD1222 for prevention of COVID-19 in immunocompromised adults.
Detailed description
The purpose of this study is to demonstrate the immunogenicity and safety of AZD1222, AstraZeneca's approved ChAdOx1 vector vaccine against SARS-CoV-2, in SARS-CoV-2 seronegative immunocompromised individuals who are unvaccinated.
Interventions
BIOLOGICALAZD1222
10 mM histidine, 7.5% (w/v) sucrose, 35 mM sodium chloride, 1 mM magnesium chloride, 0.1% (w/v) polysorbate 80, 0.1 mM edetate disodium, 0.5% (w/v) ethanol, at pH 6.6
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
Previously unvaccinated immunocompromised adults will be enrolled in 5 disease cohorts of approximately 60 participants each: 1. Solid organ transplant 2. Hematopoietic stem cell transplant 3. Solid organ cancer patients receiving cytotoxic chemotherapy 4. Chronic inflammatory disorders 5. Primary immunodeficiency A sixth cohort of immunocompetent individuals will also be recruited. Participants will be allocated to the immunocompromised cohorts according to the underlying aetiology of their immunocompromised status. Immunocompromised participants will receive a third dose (primary vaccination series) 4 weeks or more after dose 2 with AZD1222 and will continue to be followed to the end of the study. Immunocompetent participants will be eligible to receive a third dose booster 6 months after dose 1 and will continue to be followed to the end of the study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
Yes
Inclusion criteria
1. Adult, ≥ 18 years at the time of signing the informed consent. 2. Cohort specific inclusion criteria: Solid organ transplant * Participants with heart, lung, kidney, or liver transplant, and are stable on immunosuppressants (defined as no change in dose in the previous 4 weeks). Hematopoietic stem cell transplant * Participants with autologous (up to 6 months after transplantation) or allogeneic stem cell transplant who are immunosuppressed, with no evidence of active graft-versushost disease, at least one month after the procedure. Cancer patients on chemotherapy * Participants with solid tumors (except breast cancer), histologically diagnosed, who were undergoing intravenous cytotoxic chemotherapy within the last 6 months, who received at least 1 cycle prior to cytotoxic chemotherapy, and have a life expectancy of longer than 3 months. Chronic inflammatory conditions * Participants with chronic inflammatory conditions, including those on immunosuppressant medications, can be recruited. The following conditions are specifically excluded: multiple sclerosis and peripheral demyelinating disease. Primary immune deficiency * Examples include combined granulomatous disorder, SCID, common variable immunodeficiency. Immunocompetent: * No confirmed or suspected immunosuppressive or immunodeficient state. * No use of immunosuppressant medication within the past 1 month (≥ 20 mg per day of prednisone or its equivalent, given daily or on alternate days for ≥ 15 days within 30 days prior to administration of AZD1222). The following exceptions are permitted: topical/inhaled steroids or short-term oral steroids (course lasting ≤ 14 days). * No receipt of immunoglobulins and/or any blood products within 3 months prior to administration of AZD1222 or expected receipt during the period of study follow up. * No severe and/or uncontrolled cardiovascular disease, respiratory disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, and neurological illness, as judged by the Investigator.
Exclusion criteria
1. History of allergic disease or reactions likely to be exacerbated by any component of AZD1222. 2. Active infection with SARS-CoV-2 as confirmed locally by nucleic acid amplification test (e.g. RT-PCR). 3. Known current or past laboratory-confirmed SARS-CoV-2 infection. 4. Significant infection or other acute illness, including fever (temperature \> 37.8°C) on the day prior to or day of first dosing. 5. Thrombocytopenia with platelet count ≤ 75,000 x 109/microliter based on complete blood count test at screening visit. 6. HIV-positive participants based on a positive ELISA test performed at screening visit. 7. History of cerebral venous sinus thrombosis (CVST). 8. Receipt of any vaccine (licensed or investigational) within 30 days prior to and after administration of AZD1222.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Titers (GMT) for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Neutralizing Antibodies (nAb) Post 2-Dose Primary Vaccination of AZD1222 as Measured by Pseudo-neutralization Assay | Days 29 and 57 | The GMT was calculated as the antilogarithm of Σ (base 2 log transformed titer/n), that is (i.e.), as the antilogarithm transformation of the mean of the log-transformed titer, where n is the number of participants with titer information. |
| Percentage of Participants With Seroresponse to SARS-CoV-2 nAb Post 2-Dose Primary Vaccination of AZD1222 as Measured by Pseudo-neutralization Assay | Days 29 and 57 | The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level. The percentage of participants with a post-intervention seroresponse (\>=4-fold rise in titers from baseline value to 28 days post doses 1 and 2) to SARS-CoV-2 nAb of AZD1222 as measured by pseudo-neutralization assay is reported. The 2-sided 95% CI was calculated using Clopper-Pearson methodology. |
| GMT for SARS-CoV-2 Anti-Spike Binding Antibodies Post 2-Dose Primary Vaccination of AZD1222 as Measured by Meso Scale Discovery (MSD) Serology Assay | Days 29 and 57 | The GMT was calculated as the antilogarithm of Σ (base 2 log transformed titer/n), i.e, as the antilogarithm transformation of the mean of the log-transformed titer, where n is the number of participants with titer information. |
| Percentage of Participants With Seroresponse to Anti-Spike Binding Antibodies of a 2-Dose Primary Vaccination of AZD1222 as Measured by MSD Serology Assay | Days 29 and 57 | The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level. The percentage of participants with a post-intervention seroresponse (\>=4-fold rise in titers from baseline value to 28 days post doses 1 and 2) to anti-spike binding antibodies of AZD1222 as measured by MSD serology assay is reported. The 2-sided 95% CI was calculated using Clopper-Pearson methodology. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| GMT for SARS-CoV-2 nAb Post Third Dose of AZD1222 as Measured by Pseudo-neutralization Assay | Day 85 for immunocompromised cohort and Day 211 for immunocompetent cohort | The GMT was calculated as the antilogarithm of Σ (base 2 log transformed titer/n), i.e., as the antilogarithm transformation of the mean of the log-transformed titer, where n is the number of participants with titer information. The ratio of SARS-CoV-2 specific GMT titers 28 days post Dose 3 of AZD1222 was calculated as the ratio of the titer levels in the immunocompromised cohort to the immunocompetent cohort. |
| Percentage of Participants With Seroresponse to SARS-CoV-2 nAb Post Third Dose of AZD1222 as Measured by Pseudo-neutralization Assay | Day 85 for immunocompromised cohort and Day 211 for immunocompetent cohort | The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level. The percentage of participants with a post-intervention seroresponse (\>=4-fold rise in titers from baseline value to 28 days post dose 3) to SARS-CoV-2 nAb of AZD1222 as measured by pseudo-neutralization assay is reported, and the 2-sided 95% CI was calculated using Clopper-Pearson methodology. The difference in seroresponse 28 days post Dose 3 of AZD1222 was calculated as (seroresponse rate of immunocompromised cohort) - (seroresponse rate of immunocompetent cohort). |
| GMT for SARS-CoV-2 nAb Post Second Dose of AZD1222 as Measured by Pseudo-neutralization Assay | Day 57 | The GMT was calculated as the antilogarithm of Σ (base 2 log transformed titer/n), i.e., as the antilogarithm transformation of the mean of the log-transformed titer, where n is the number of participants with titer information. The ratio of SARS-CoV-2 specific GMT titers 28 days post Dose 2 of AZD1222 was calculated as the ratio of the titer levels in the immunocompromised cohort to the immunocompetent cohort. |
| Percentage of Participants With Seroresponse to Anti-Spike Binding Antibodies Post Third Dose of AZD1222 as Measured by MSD Serology Assay | Day 85 for immunocompromised cohort and Day 211 for immunocompetent cohort | The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level. The percentage of participants with a post-intervention seroresponse (\>=4-fold rise in titers from baseline value to 28 days post dose 3) to anti-spike binding antibodies of AZD1222 as measured by MSD serology assay is reported, and the 2-sided 95% CI was calculated using Clopper-Pearson methodology. The difference in seroresponse 28 days post Dose 3 of AZD1222 was calculated as (seroresponse rate of immunocompromised cohort) - (seroresponse rate of immunocompetent cohort). |
| GMT for SARS-CoV-2 Anti-Spike Binding Antibodies Post Third Dose of AZD1222 as Measured by MSD Serology Assay | Day 85 for immunocompromised cohort and Day 211 for immunocompetent cohort | The GMT was calculated as the antilogarithm of Σ (base 2 log transformed titer/n), i.e., as the antilogarithm transformation of the mean of the log-transformed titer, where n is the number of participants with titer information. The ratio of SARS-CoV-2 specific GMT titers 28 days post Dose 3 of AZD1222 was calculated as the ratio of the titer levels in the immunocompromised cohort to the immunocompetent cohort. |
| Percentage of Participants With Seroresponse to SARS-CoV-2 nAb Post Second Dose of AZD1222 as Measured by Pseudo-neutralization Assay | Day 57 | The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level. The percentage of participants with a post-intervention seroresponse (\>=4-fold rise in titers from baseline value to 28 days post Dose 2) to SARS-CoV-2 nAb of AZD1222 as measured by pseudo-neutralization assay is reported, and the 2-sided 95% CI was calculated using Clopper-Pearson methodology. The difference in seroresponse 28 days post Dose 2 of AZD1222 was calculated as (seroresponse rate of immunocompromised cohort) - (seroresponse rate of immunocompetent cohort), and the 2-sided 95% CI was calculated using the Newcombe score without continuity correction. |
| GMT for SARS-CoV-2 Anti-Spike Binding Antibodies Post Second Dose of AZD1222 as Measured by MSD Serology Assay | Day 57 | The GMT was calculated as the antilogarithm of Σ (base 2 log transformed titer/n), i.e., as the antilogarithm transformation of the mean of the log-transformed titer, where n is the number of participants with titer information. The ratio of SARS-CoV-2 specific GMT titers 28 days post Dose 2 of AZD1222 was calculated as the ratio of the titer levels in the immunocompromised cohort to the immunocompetent cohort. |
| Percentage of Participants With Seroresponse to SARS-CoV-2 Anti-Spike Binding Antibodies Post Second Dose of AZD1222 as Measured by MSD Serology Assay | Day 57 | The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level. The percentage of participants with a post-intervention seroresponse (\>=4-fold rise in titers from baseline value to 28 days post Dose 2) to SARS-CoV-2 nAb of AZD1222 as measured by MSD Serology assay is reported, and the 2-sided 95% CI was calculated using Clopper-Pearson methodology. The difference in seroresponse 28 days post Dose 2 of AZD1222 was calculated as (seroresponse rate of immunocompromised cohort) - (seroresponse rate of immunocompetent cohort), and the 2-sided 95% CI was calculated using the Newcombe score without continuity correction. |
Countries
Thailand, Ukraine
Participant flow
Recruitment details
This Phase IV open-label study was conducted in previously unvaccinated immunocompromised adult participants at 4 sites in Ukraine and Thailand between 31 Jan 2022 and 19 Apr 2023. The study was terminated prematurely due to recruitment challenges, resulting in low sample sizes, especially in the immunocompromised cohorts. Hence, analyses were streamlined.
Pre-assignment details
This study consisted of a screening period (up to 7 days) and a vaccination/follow-up period (up to 365 days). The study was planned to involve a total of 6 cohorts: 5 immunocompromised cohorts (including participants with solid organ transplant, hematopoietic stem cell transplant, solid organ cancer participants receiving cytotoxic chemotherapy, chronic inflammatory disorders and primary immunodeficiency) and 1 immunocompetent cohort.
Participants by arm
| Arm | Count |
|---|---|
| Immunocompromised Cohort Participants received 3 IM doses of AZD1222 5 × 10\^10 vp on Days 1, 29 and 57. | 11 |
| Immunocompetent Cohort Participants received 3 IM doses of AZD1222 5 × 10\^10 vp on Days 1, 29 and 183. | 23 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 0 |
| Overall Study | Site closure | 2 | 2 |
Baseline characteristics
| Characteristic | Immunocompromised Cohort | Immunocompetent Cohort | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 2 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 21 Participants | 28 Participants |
| Race/Ethnicity, Customized Asian | 9 Participants | 21 Participants | 30 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 11 Participants | 23 Participants | 34 Participants |
| Race/Ethnicity, Customized White | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Female | 7 Participants | 11 Participants | 18 Participants |
| Sex: Female, Male Male | 4 Participants | 12 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 11 | 0 / 23 |
| other Total, other adverse events | 7 / 11 | 11 / 23 |
| serious Total, serious adverse events | 1 / 11 | 4 / 23 |
Outcome results
Primary
Geometric Mean Titers (GMT) for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Neutralizing Antibodies (nAb) Post 2-Dose Primary Vaccination of AZD1222 as Measured by Pseudo-neutralization Assay
The GMT was calculated as the antilogarithm of Σ (base 2 log transformed titer/n), that is (i.e.), as the antilogarithm transformation of the mean of the log-transformed titer, where n is the number of participants with titer information.
Time frame: Days 29 and 57
Population: The Immunogenicity Analysis set (IAS) consisted of all participants in the Safety Analysis set who had at least 1 baseline and post-baseline record in immunogenicity data and no protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response. Only those participants with data available were included in the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Immunocompromised Cohort | Geometric Mean Titers (GMT) for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Neutralizing Antibodies (nAb) Post 2-Dose Primary Vaccination of AZD1222 as Measured by Pseudo-neutralization Assay | Day 29 | 47.7 1/dilution |
| Immunocompromised Cohort | Geometric Mean Titers (GMT) for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Neutralizing Antibodies (nAb) Post 2-Dose Primary Vaccination of AZD1222 as Measured by Pseudo-neutralization Assay | Day 57 | 122.0 1/dilution |
| Immunocompetent Cohort | Geometric Mean Titers (GMT) for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Neutralizing Antibodies (nAb) Post 2-Dose Primary Vaccination of AZD1222 as Measured by Pseudo-neutralization Assay | Day 29 | 67.9 1/dilution |
| Immunocompetent Cohort | Geometric Mean Titers (GMT) for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Neutralizing Antibodies (nAb) Post 2-Dose Primary Vaccination of AZD1222 as Measured by Pseudo-neutralization Assay | Day 57 | 166.5 1/dilution |
Primary
GMT for SARS-CoV-2 Anti-Spike Binding Antibodies Post 2-Dose Primary Vaccination of AZD1222 as Measured by Meso Scale Discovery (MSD) Serology Assay
The GMT was calculated as the antilogarithm of Σ (base 2 log transformed titer/n), i.e, as the antilogarithm transformation of the mean of the log-transformed titer, where n is the number of participants with titer information.
Time frame: Days 29 and 57
Population: The IAS consisted of all participants in the Safety Analysis set who had at least 1 baseline and post-baseline record in immunogenicity data and no protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response. Only those participants with data available were included in the analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Immunocompromised Cohort | GMT for SARS-CoV-2 Anti-Spike Binding Antibodies Post 2-Dose Primary Vaccination of AZD1222 as Measured by Meso Scale Discovery (MSD) Serology Assay | Day 57 | 13262.8 arbitrary units (AU)/milliliter (mL) |
| Immunocompromised Cohort | GMT for SARS-CoV-2 Anti-Spike Binding Antibodies Post 2-Dose Primary Vaccination of AZD1222 as Measured by Meso Scale Discovery (MSD) Serology Assay | Day 29 | 3997.2 arbitrary units (AU)/milliliter (mL) |
| Immunocompetent Cohort | GMT for SARS-CoV-2 Anti-Spike Binding Antibodies Post 2-Dose Primary Vaccination of AZD1222 as Measured by Meso Scale Discovery (MSD) Serology Assay | Day 29 | 19134.7 arbitrary units (AU)/milliliter (mL) |
| Immunocompetent Cohort | GMT for SARS-CoV-2 Anti-Spike Binding Antibodies Post 2-Dose Primary Vaccination of AZD1222 as Measured by Meso Scale Discovery (MSD) Serology Assay | Day 57 | 28320.9 arbitrary units (AU)/milliliter (mL) |
Primary
Percentage of Participants With Seroresponse to Anti-Spike Binding Antibodies of a 2-Dose Primary Vaccination of AZD1222 as Measured by MSD Serology Assay
The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level. The percentage of participants with a post-intervention seroresponse (\>=4-fold rise in titers from baseline value to 28 days post doses 1 and 2) to anti-spike binding antibodies of AZD1222 as measured by MSD serology assay is reported. The 2-sided 95% CI was calculated using Clopper-Pearson methodology.
Time frame: Days 29 and 57
Population: The IAS consisted of all participants in the Safety Analysis set who had at least 1 baseline and post-baseline record in immunogenicity data and no protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response. Only those participants with data available were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Immunocompromised Cohort | Percentage of Participants With Seroresponse to Anti-Spike Binding Antibodies of a 2-Dose Primary Vaccination of AZD1222 as Measured by MSD Serology Assay | Day 29 | 88.9 percentage of participants |
| Immunocompromised Cohort | Percentage of Participants With Seroresponse to Anti-Spike Binding Antibodies of a 2-Dose Primary Vaccination of AZD1222 as Measured by MSD Serology Assay | Day 57 | 75.0 percentage of participants |
| Immunocompetent Cohort | Percentage of Participants With Seroresponse to Anti-Spike Binding Antibodies of a 2-Dose Primary Vaccination of AZD1222 as Measured by MSD Serology Assay | Day 29 | 100 percentage of participants |
| Immunocompetent Cohort | Percentage of Participants With Seroresponse to Anti-Spike Binding Antibodies of a 2-Dose Primary Vaccination of AZD1222 as Measured by MSD Serology Assay | Day 57 | 100 percentage of participants |
Primary
Percentage of Participants With Seroresponse to SARS-CoV-2 nAb Post 2-Dose Primary Vaccination of AZD1222 as Measured by Pseudo-neutralization Assay
The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level. The percentage of participants with a post-intervention seroresponse (\>=4-fold rise in titers from baseline value to 28 days post doses 1 and 2) to SARS-CoV-2 nAb of AZD1222 as measured by pseudo-neutralization assay is reported. The 2-sided 95% CI was calculated using Clopper-Pearson methodology.
Time frame: Days 29 and 57
Population: The IAS consisted of all participants in the Safety Analysis set who had at least 1 baseline and post-baseline record in immunogenicity data and no protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response. Only those participants with data available were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Immunocompromised Cohort | Percentage of Participants With Seroresponse to SARS-CoV-2 nAb Post 2-Dose Primary Vaccination of AZD1222 as Measured by Pseudo-neutralization Assay | Day 29 | 22.2 percentage of participants |
| Immunocompromised Cohort | Percentage of Participants With Seroresponse to SARS-CoV-2 nAb Post 2-Dose Primary Vaccination of AZD1222 as Measured by Pseudo-neutralization Assay | Day 57 | 62.5 percentage of participants |
| Immunocompetent Cohort | Percentage of Participants With Seroresponse to SARS-CoV-2 nAb Post 2-Dose Primary Vaccination of AZD1222 as Measured by Pseudo-neutralization Assay | Day 29 | 44.4 percentage of participants |
| Immunocompetent Cohort | Percentage of Participants With Seroresponse to SARS-CoV-2 nAb Post 2-Dose Primary Vaccination of AZD1222 as Measured by Pseudo-neutralization Assay | Day 57 | 92.9 percentage of participants |
Secondary
GMT for SARS-CoV-2 Anti-Spike Binding Antibodies Post Second Dose of AZD1222 as Measured by MSD Serology Assay
The GMT was calculated as the antilogarithm of Σ (base 2 log transformed titer/n), i.e., as the antilogarithm transformation of the mean of the log-transformed titer, where n is the number of participants with titer information. The ratio of SARS-CoV-2 specific GMT titers 28 days post Dose 2 of AZD1222 was calculated as the ratio of the titer levels in the immunocompromised cohort to the immunocompetent cohort.
Time frame: Day 57
Population: The IAS consisted of all participants in the Safety Analysis set who had at least 1 baseline and post-baseline record in immunogenicity data and no protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response. Only those participants with data available were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Immunocompromised Cohort | GMT for SARS-CoV-2 Anti-Spike Binding Antibodies Post Second Dose of AZD1222 as Measured by MSD Serology Assay | 13262.8 arbitrary units (AU)/milliliters (mL) |
| Immunocompetent Cohort | GMT for SARS-CoV-2 Anti-Spike Binding Antibodies Post Second Dose of AZD1222 as Measured by MSD Serology Assay | 28320.9 arbitrary units (AU)/milliliters (mL) |
Comparison: Day 57 (28 days post Dose 2)95% CI: [0.06, 3.86]
Secondary
GMT for SARS-CoV-2 Anti-Spike Binding Antibodies Post Third Dose of AZD1222 as Measured by MSD Serology Assay
The GMT was calculated as the antilogarithm of Σ (base 2 log transformed titer/n), i.e., as the antilogarithm transformation of the mean of the log-transformed titer, where n is the number of participants with titer information. The ratio of SARS-CoV-2 specific GMT titers 28 days post Dose 3 of AZD1222 was calculated as the ratio of the titer levels in the immunocompromised cohort to the immunocompetent cohort.
Time frame: Day 85 for immunocompromised cohort and Day 211 for immunocompetent cohort
Population: The IAS consisted of all participants in the Safety Analysis set who had at least 1 baseline and post-baseline record in immunogenicity data and no protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response. Only those participants with data available were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Immunocompromised Cohort | GMT for SARS-CoV-2 Anti-Spike Binding Antibodies Post Third Dose of AZD1222 as Measured by MSD Serology Assay | 48303.4 arbitrary units (AU)/milliliters (mL) |
| Immunocompetent Cohort | GMT for SARS-CoV-2 Anti-Spike Binding Antibodies Post Third Dose of AZD1222 as Measured by MSD Serology Assay | 86462.9 arbitrary units (AU)/milliliters (mL) |
Comparison: Day 85 Immunocompromised / Day 211 Immunocompetent (28 days post Dose 3)95% CI: [0.25, 1.25]
Secondary
GMT for SARS-CoV-2 nAb Post Second Dose of AZD1222 as Measured by Pseudo-neutralization Assay
The GMT was calculated as the antilogarithm of Σ (base 2 log transformed titer/n), i.e., as the antilogarithm transformation of the mean of the log-transformed titer, where n is the number of participants with titer information. The ratio of SARS-CoV-2 specific GMT titers 28 days post Dose 2 of AZD1222 was calculated as the ratio of the titer levels in the immunocompromised cohort to the immunocompetent cohort.
Time frame: Day 57
Population: The IAS consisted of all participants in the Safety Analysis set who had at least 1 baseline and post-baseline record in immunogenicity data and no protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response. Only those participants with data available were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Immunocompromised Cohort | GMT for SARS-CoV-2 nAb Post Second Dose of AZD1222 as Measured by Pseudo-neutralization Assay | 122.0 1/dilution |
| Immunocompetent Cohort | GMT for SARS-CoV-2 nAb Post Second Dose of AZD1222 as Measured by Pseudo-neutralization Assay | 166.5 1/dilution |
Comparison: Day 57 (28 days post Dose 2)95% CI: [0.18, 3.01]
Secondary
GMT for SARS-CoV-2 nAb Post Third Dose of AZD1222 as Measured by Pseudo-neutralization Assay
The GMT was calculated as the antilogarithm of Σ (base 2 log transformed titer/n), i.e., as the antilogarithm transformation of the mean of the log-transformed titer, where n is the number of participants with titer information. The ratio of SARS-CoV-2 specific GMT titers 28 days post Dose 3 of AZD1222 was calculated as the ratio of the titer levels in the immunocompromised cohort to the immunocompetent cohort.
Time frame: Day 85 for immunocompromised cohort and Day 211 for immunocompetent cohort
Population: The IAS consisted of all participants in the Safety Analysis set who had at least 1 baseline and post-baseline record in immunogenicity data and no protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response. Only those participants with data available were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Immunocompromised Cohort | GMT for SARS-CoV-2 nAb Post Third Dose of AZD1222 as Measured by Pseudo-neutralization Assay | 224.5 1/dilution |
| Immunocompetent Cohort | GMT for SARS-CoV-2 nAb Post Third Dose of AZD1222 as Measured by Pseudo-neutralization Assay | 710.3 1/dilution |
Comparison: Day 85 Immunocompromised / Day 211 Immunocompetent (28 days post Dose 3)95% CI: [0.12, 0.8]
Secondary
Percentage of Participants With Seroresponse to Anti-Spike Binding Antibodies Post Third Dose of AZD1222 as Measured by MSD Serology Assay
The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level. The percentage of participants with a post-intervention seroresponse (\>=4-fold rise in titers from baseline value to 28 days post dose 3) to anti-spike binding antibodies of AZD1222 as measured by MSD serology assay is reported, and the 2-sided 95% CI was calculated using Clopper-Pearson methodology. The difference in seroresponse 28 days post Dose 3 of AZD1222 was calculated as (seroresponse rate of immunocompromised cohort) - (seroresponse rate of immunocompetent cohort).
Time frame: Day 85 for immunocompromised cohort and Day 211 for immunocompetent cohort
Population: The IAS consisted of all participants in the Safety Analysis set who had at least 1 baseline and post-baseline record in immunogenicity data and no protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response. Only those participants with data available were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immunocompromised Cohort | Percentage of Participants With Seroresponse to Anti-Spike Binding Antibodies Post Third Dose of AZD1222 as Measured by MSD Serology Assay | 100 percentage of participants |
| Immunocompetent Cohort | Percentage of Participants With Seroresponse to Anti-Spike Binding Antibodies Post Third Dose of AZD1222 as Measured by MSD Serology Assay | 100 percentage of participants |
Comparison: Day 85 Immunocompromised / Day 211 Immunocompetent (28 days post Dose 3)
Secondary
Percentage of Participants With Seroresponse to SARS-CoV-2 Anti-Spike Binding Antibodies Post Second Dose of AZD1222 as Measured by MSD Serology Assay
The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level. The percentage of participants with a post-intervention seroresponse (\>=4-fold rise in titers from baseline value to 28 days post Dose 2) to SARS-CoV-2 nAb of AZD1222 as measured by MSD Serology assay is reported, and the 2-sided 95% CI was calculated using Clopper-Pearson methodology. The difference in seroresponse 28 days post Dose 2 of AZD1222 was calculated as (seroresponse rate of immunocompromised cohort) - (seroresponse rate of immunocompetent cohort), and the 2-sided 95% CI was calculated using the Newcombe score without continuity correction.
Time frame: Day 57
Population: The IAS consisted of all participants in the Safety Analysis set who had at least 1 baseline and post-baseline record in immunogenicity data and no protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response. Only those participants with data available were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immunocompromised Cohort | Percentage of Participants With Seroresponse to SARS-CoV-2 Anti-Spike Binding Antibodies Post Second Dose of AZD1222 as Measured by MSD Serology Assay | 75.0 percentage of participants |
| Immunocompetent Cohort | Percentage of Participants With Seroresponse to SARS-CoV-2 Anti-Spike Binding Antibodies Post Second Dose of AZD1222 as Measured by MSD Serology Assay | 100 percentage of participants |
Comparison: Day 57 (28 days post Dose 2)95% CI: [-59.07, 2.97]
Secondary
Percentage of Participants With Seroresponse to SARS-CoV-2 nAb Post Second Dose of AZD1222 as Measured by Pseudo-neutralization Assay
The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level. The percentage of participants with a post-intervention seroresponse (\>=4-fold rise in titers from baseline value to 28 days post Dose 2) to SARS-CoV-2 nAb of AZD1222 as measured by pseudo-neutralization assay is reported, and the 2-sided 95% CI was calculated using Clopper-Pearson methodology. The difference in seroresponse 28 days post Dose 2 of AZD1222 was calculated as (seroresponse rate of immunocompromised cohort) - (seroresponse rate of immunocompetent cohort), and the 2-sided 95% CI was calculated using the Newcombe score without continuity correction.
Time frame: Day 57
Population: The IAS consisted of all participants in the Safety Analysis set who had at least 1 baseline and post-baseline record in immunogenicity data and no protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response. Only those participants with data available were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immunocompromised Cohort | Percentage of Participants With Seroresponse to SARS-CoV-2 nAb Post Second Dose of AZD1222 as Measured by Pseudo-neutralization Assay | 62.5 percentage of participants |
| Immunocompetent Cohort | Percentage of Participants With Seroresponse to SARS-CoV-2 nAb Post Second Dose of AZD1222 as Measured by Pseudo-neutralization Assay | 92.9 percentage of participants |
Comparison: Day 57 (28 days post Dose 2)95% CI: [-62.82, 3.69]
Secondary
Percentage of Participants With Seroresponse to SARS-CoV-2 nAb Post Third Dose of AZD1222 as Measured by Pseudo-neutralization Assay
The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level. The percentage of participants with a post-intervention seroresponse (\>=4-fold rise in titers from baseline value to 28 days post dose 3) to SARS-CoV-2 nAb of AZD1222 as measured by pseudo-neutralization assay is reported, and the 2-sided 95% CI was calculated using Clopper-Pearson methodology. The difference in seroresponse 28 days post Dose 3 of AZD1222 was calculated as (seroresponse rate of immunocompromised cohort) - (seroresponse rate of immunocompetent cohort).
Time frame: Day 85 for immunocompromised cohort and Day 211 for immunocompetent cohort
Population: The IAS consisted of all participants in the Safety Analysis set who had at least 1 baseline and post-baseline record in immunogenicity data and no protocol deviations judged to have the potential to interfere with the generation or interpretation of an immune response. Only those participants with data available were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Immunocompromised Cohort | Percentage of Participants With Seroresponse to SARS-CoV-2 nAb Post Third Dose of AZD1222 as Measured by Pseudo-neutralization Assay | 100 percentage of participants |
| Immunocompetent Cohort | Percentage of Participants With Seroresponse to SARS-CoV-2 nAb Post Third Dose of AZD1222 as Measured by Pseudo-neutralization Assay | 100 percentage of participants |
Comparison: Day 85 Immunocompromised / Day 211 Immunocompetent (28 days post Dose 3)