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

NCT05057897 | Terminated Phase 4 Results

• 1 other identifier: D8111C00010
• Study Type: interventional
• Target: 34
• Locations: 2 countries
• Sites: 4

Brief Summary

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

Conditions

COVID-19, SARS-CoV-2

Keywords

COVID-19 Vaccine

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (8)

• GMT for SARS-CoV-2 nAb Post Second Dose of AZD1222 as Measured by Pseudo-neutralization Assay

  Day 57

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

  Day 57

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

  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

  Day 57

• 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

Study Arms (6)

Cohort 1 - immunocompromised participants with solid organ transplant

OTHER

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

Cohort 2 - immunocompromised participants with hematopoietic stem cell transplant

OTHER

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

Cohort 3 - immunocompromised participants with solid organ cancer receiving cytotoxic chemotherapy

OTHER

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

Cohort 4 - immunocompromised participants with chronic inflammatory disorders

OTHER

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

Cohort 5 - immunocompromised participants with primary immunodeficiency

OTHER

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

Cohort 6 - immunocompetent participants

OTHER

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

Interventions

AZD1222 BIOLOGICAL

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

Cohort 1 - immunocompromised participants with solid organ transplant; Cohort 2 - immunocompromised participants with hematopoietic stem cell transplant; Cohort 3 - immunocompromised participants with solid organ cancer receiving cytotoxic chemotherapy; Cohort 4 - immunocompromised participants with chronic inflammatory disorders; Cohort 5 - immunocompromised participants with primary immunodeficiency; Cohort 6 - immunocompetent participants

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult, ≥ 18 years at the time of signing the informed consent.
• 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.

You may not qualify if:

• History of allergic disease or reactions likely to be exacerbated by any component of AZD1222.
• Active infection with SARS-CoV-2 as confirmed locally by nucleic acid amplification test (e.g. RT-PCR).
• Known current or past laboratory-confirmed SARS-CoV-2 infection.
• Significant infection or other acute illness, including fever (temperature \> 37.8°C) on the day prior to or day of first dosing.
• Thrombocytopenia with platelet count ≤ 75,000 x 109/microliter based on complete blood count test at screening visit.
• HIV-positive participants based on a positive ELISA test performed at screening visit.
• History of cerebral venous sinus thrombosis (CVST).
• Receipt of any vaccine (licensed or investigational) within 30 days prior to and after administration of AZD1222.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (4)

Research Site

Bangkok, 10700, Thailand

Location

Research Site

Khon Kaen, 40002, Thailand

Location

Research Site

Muang, 50200, Thailand

Location

Research Site

Kharkiv, 61052, Ukraine

Location

Related Links

• Redacted CSR Synopsis

MeSH Terms

Conditions

COVID-19

Interventions

ChAdOx1 nCoV-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Vaccines, DNA; Nucleic Acid-Based Vaccines; Vaccines, Synthetic; Vaccines; Biological Products; Complex Mixtures; COVID-19 Vaccines; Viral Vaccines

Limitations and Caveats

The study was terminated prematurely due to recruitment challenges, resulting in low sample sizes, especially in the immunocompromised cohorts. Hence, all outcome measures, including comparisons between cohorts, should be interpreted with caution.

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 15, 2021
• First Posted: September 27, 2021
• Study Start: January 31, 2022
• Primary Completion: April 19, 2023
• Study Completion: April 19, 2023
• Last Updated: January 27, 2025
• Results First Posted: January 27, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• 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
• 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

Locations

UA (1); TH (3)