A Study of AZD1222, a Vaccine for the Prevention of COVID-19 in Immunocompromised Adults

Phase 4TerminatedNCT05057897

AstraZeneca34 enrolled

Overview

The aim of this study is to assess the immunogenicity and safety of AZD1222 for prevention of COVID-19 in immunocompromised adults.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

Conditions

COVID-19, SARS-CoV-2

Interventions

AZD1222BIOLOGICAL

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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 130 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (4)

Research Site

Bangkok, Thailand

Research Site

Khon Kaen, Thailand

Research Site

Muang, Thailand

Research Site

Kharkiv, Ukraine

Outcomes

Primary Outcomes

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

Percentage of Participants With Seroresponse to SARS-CoV-2 nAb Post 2-Dose Primary Vaccination of AZD1222 as Measured by Pseudo-neutralization Assay

Time frame: Days 29 and 57

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

Percentage of Participants With Seroresponse to Anti-Spike Binding Antibodies of a 2-Dose Primary Vaccination of AZD1222 as Measured by MSD Serology Assay

Time frame: Days 29 and 57

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Secondary Outcomes

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

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

GMT for SARS-CoV-2 Anti-Spike Binding Antibodies Post Second Dose of AZD1222 as Measured by MSD Serology Assay

Time frame: Day 57

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

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

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

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

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