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

A Phase IV Open-Label, Non-Randomized, Multi-Cohort, Multicenter Study in Previously Unvaccinated Immunocompromised Adults to Determine the Immunogenicity and Safety of AZD1222 Vaccine for the Prevention of COVID-19

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

Study Overview

• Status: Terminated
• Conditions: COVID-19, SARS-CoV-2
• Intervention / Treatment: Biological: AZD1222

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.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 4

Contacts and Locations

Study Locations

• Thailand
  • Bangkok, Thailand, 10700
    • Research Site
  • Khon Kaen, Thailand, 40002
    • Research Site
  • Muang, Thailand, 50200
    • Research Site
• Ukraine
  • Kharkiv, Ukraine, 61052
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Cohort 1 - immunocompromised participants with solid organ transplant; Previously unvaccinated immunocompromised participants with solid organ transplant will receive a primary vaccination series with 3 IM doses of AZD1222 separated by 4 weeks and will be followed to the end of the study. The first dose will be administered on Day 1, the second dose will be administered 28 days after dose 1, and the third dose will be administered 28 days after dose 2.	Biological: AZD1222; 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
Other: Cohort 2 - immunocompromised participants with hematopoietic stem cell transplant; Previously unvaccinated immunocompromised participants with hematopoietic stem cell transplant will receive a primary vaccination series with 3 IM doses of AZD1222 separated by 4 weeks and will be followed to the end of the study. The first dose will be administered on Day 1, the second dose will be administered 28 days after dose 1, and the third dose will be administered 28 days after dose 2.	Biological: AZD1222; 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
Other: Cohort 3 - immunocompromised participants with solid organ cancer receiving cytotoxic chemotherapy; Previously unvaccinated immunocompromised participants with solid organ cancer receiving cytotoxic chemotherapy will receive a primary vaccination series with 3 IM doses of AZD1222 separated by 4 weeks and will be followed to the end of the study. The first dose will be administered on Day 1, the second dose will be administered 28 days after dose 1, and the third dose will be administered 28 days after dose 2.	Biological: AZD1222; 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
Other: Cohort 4 - immunocompromised participants with chronic inflammatory disorders; Previously unvaccinated immunocompromised participants with chronic inflammatory disorders will receive a primary vaccination series with 3 IM doses of AZD1222 separated by 4 weeks and will be followed to the end of the study. The first dose will be administered on Day 1, the second dose will be administered 28 days after dose 1, and the third dose will be administered 28 days after dose 2.	Biological: AZD1222; 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
Other: Cohort 5 - immunocompromised participants with primary immunodeficiency; Previously unvaccinated immunocompromised participants with primary immunodeficiency will receive a primary vaccination series with 3 IM doses of AZD1222 separated by 4 weeks and will be followed to the end of the study. The first dose will be administered on Day 1, the second dose will be administered 28 days after dose 1, and the third dose will be administered 28 days after dose 2.	Biological: AZD1222; 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
Other: Cohort 6 - immunocompetent participants; Previously unvaccinated immunocompetent participants will receive a primary vaccination series with 2 IM doses of AZD1222 separated by 4 weeks, followed by a booster dose of AZD1222 administered 6 months after the first dose. The first dose will be administered on Day 1, the second dose will be administered 28 days after dose 1. Participants will receive a third dose booster 6 months after dose 1 and will continue to be followed to the end of the study.	Biological: AZD1222; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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	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.	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.	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	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.	Days 29 and 57

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	Day 57
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.	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.	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.	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).	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.	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).	Day 85 for immunocompromised cohort and Day 211 for immunocompetent cohort

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

Helpful Links

• Redacted CSR Synopsis

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2022
• Primary Completion (Actual): April 19, 2023
• Study Completion (Actual): April 19, 2023

Study Registration Dates

• First Submitted: September 15, 2021
• First Submitted That Met QC Criteria: September 24, 2021
• First Posted (Actual): September 27, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 20, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: COVID-19 Vaccine
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19
• Other Study ID Numbers: D8111C00010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No