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Phase II/III Study of AZD2816, for the Prevention of COVID-19 in Adults (AZD2816)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04973449
Recruitment Status : Completed
First Posted : July 22, 2021
Last Update Posted : January 18, 2023
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE July 2, 2021
First Posted Date  ICMJE July 22, 2021
Last Update Posted Date January 18, 2023
Actual Study Start Date  ICMJE June 27, 2021
Actual Primary Completion Date February 4, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 28, 2021)
  • The safety and tolerability of 1 dose of AZD2816 in the previously vaccinated cohort with AZD1222 [ Time Frame: for 7 days ]
    Incidence of local and systemic solicited AEs
  • The safety and tolerability of 1 dose of AZD2816 in the previously vaccinated cohort with AZD1222 [ Time Frame: 28 days post dose ]
    The change from baseline for safety laboratory measures Incidence of unsolicited AEs, including MAAEs, SAEs, and AESIs,
  • The safety and tolerability of a 2-dose primary vaccination with AZD2816 in the unvaccinated cohort [ Time Frame: for 7 days ]
    Incidence of local and systemic solicited AEs
  • The safety and tolerability of a 2-dose primary vaccination with AZD2816 in the unvaccinated cohort [ Time Frame: 28 days post dose ]
    The change from baseline for safety laboratory measures Incidence of unsolicited AEs, including MAAEs, SAEs, and AESIs
  • To determine if the response against B.1.351 elicited by an AZD2816 booster dose in participants previously vaccinated with AZD1222 is non-inferior to the response against Wuhan-Hu-1 strain elicited by 2-dose AZD1222 administered to naïve participants [ Time Frame: 28 days post second dose ]
    GMT ratio of pseudoneutralizing antibodies for AZD2816 booster/AZD1222 vaccination
  • To determine if the response against the B.1.351 variant elicited by a 2-dose AZD2816 vaccination is non-inferior to the response against the original Wuhan-Hu-1 strain elicited by a 2-dose AZD1222 vaccination in the unvaccinated cohort [ Time Frame: 28 days post second dose ]
    GMT ratio of pseudoneutralizing antibodies for AZD2816 vaccination/AZD1222 Vaccination
Original Primary Outcome Measures  ICMJE
 (submitted: July 21, 2021)
  • The safety and tolerability of 1 dose of AZD2816 in seronegative participants previously vaccinated with AZD1222 [ Time Frame: for 7 days ]
    Incidence of local and systemic solicited AEs
  • The safety and tolerability of 1 dose of AZD2816 in seronegative participants previously vaccinated with AZD1222 [ Time Frame: 28 days post dose ]
    The change from baseline for safety laboratory measures
  • The safety and tolerability of a 2-dose primary vaccination with AZD2816 in unvaccinated seronegative participants [ Time Frame: for 7 days ]
    Incidence of local and systemic solicited AEs
  • The safety and tolerability of a 2-dose primary vaccination with AZD2816 in unvaccinated seronegative participants [ Time Frame: 28 days post dose ]
    Incidence of unsolicited AEs, including MAAEs, SAEs, and AESIs
  • The safety and tolerability of a 2-dose primary vaccination with AZD2816 in unvaccinated seronegative participants [ Time Frame: 28 days post dose ]
    The change from baseline for safety laboratory measures
  • Describe the humoral immune responses against the B.1.351 and Wuhan-Hu-1 strains induced by 1 dose of AZD2816 in seronegative participants previously vaccinated with AZD1222/SARS-CoV-2 mRNA vaccine [ Time Frame: 28 days post dose ]
    Magnitude of SARS-CoV-2 specific antibody binding and neutralization titres (geometric mean titre) Seroresponse rate of SARS-CoV-2 specific antibody binding and neutralization titres
  • Describe the humoral immune responses against the B.1.351 and Wuhan-Hu-1 strains induced by a 2-dose primary vaccination with AZD2816 in unvaccinated seronegative participants [ Time Frame: 28 days post second dose ]
    Magnitude of SARS-CoV-2 specific antibody binding and neutralization titres (geometric mean titre) Seroresponse rate of SARS-CoV-2 specific antibody binding and neutralization titres
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 28, 2021)
  • To determine if seroresponse against the B.1.351 variant elicited by a 2-dose AZD2816 vaccination is non-inferior to seroresponse against the original WuHan-hu-1 strain elicited by a 2-dose AZD1222 vaccination in the unvaccinated cohort [ Time Frame: 28 days post second dose ]
    Difference in seroresponse rates
  • To determine if the neutralizing antibody GMT response against the B.1.351 variant elicited by a 2-dose AZD2816 vaccination is non-inferior to the response elicited by a 2-dose AZD1222 vaccination in the unvaccinated cohort [ Time Frame: 28 days post second dose ]
    GMT ratio of pseudoneutralizing antibodies
  • To determine if the response against the B.1.351 variant elicited by AZD1222 + AZD2816 vaccination is non-inferior to the response against the Wuhan-Hu-1 strain elicited by AZD1222 in the unvaccinated cohort [ Time Frame: 28 days post second dose ]
    GMT ratio of pseudoneutralizing antibodies
  • To determine if the neutralizing antibody GMT response against the original Wuhan-Hu-1 elicited by a 2-dose AZD2816 vaccination is non-inferior to the response elicited by a 2-dose AZD1222 vaccination [ Time Frame: 28 days post second dose ]
    GMT ratio of pseudoneutralizing antibodies
  • To determine if the response against B.1.351 elicited by an AZD2816 booster dose in participants previously vaccinated with AZD1222 is non-inferior to the response elicited by 2-dose AZD1222 vaccination administered to vaccination naïve participants [ Time Frame: 28 days post second dose ]
    GMT ratio of pseudoneutralizing antibodies Difference in seroresponse rates
  • To determine if the humoral immune response elicited against the B.1.351 variant by an AZD2816 booster dose is non-inferior to the response elicited by an AZD1222 booster dose in participants previously vaccinated with AZD1222 [ Time Frame: 28 days post second dose ]
    GMT ratio of pseudoneutralizing antibodies Difference in seroresponse rates
  • To determine if the response against the WuHan-hu-1 strain elicited by an AZD2816 booster in participants previously vaccinated with AZD1222 is non-inferior to the response elicited by 2-dose AZD1222 administered to vaccination naïve participants [ Time Frame: 28 days post second dose ]
    GMT ratio of pseudoneutralizing antibodies Difference in seroresponse rates
  • To determine if the humoral immune response against the original WuHan-hu-1 strain elicited by an AZD1222 booster dose in participants previously vaccinated with AZD1222 is non-inferior to the response elicited by a 2-dose AZD1222 vaccination [ Time Frame: 28 days post second dose ]
    GMT ratio of pseudoneutralizing antibodies Difference in seroresponse rates
  • To determine if the humoral immune response against the original WuHan-hu-1 strain elicited by an AZD2816 booster dose is non-inferior to the response elicited by an AZD1222 booster dose in participants previously vaccinated with AZD1222 [ Time Frame: 28 days post second dose ]
    GMT ratio of pseudoneutralizing antibodies
Original Secondary Outcome Measures  ICMJE
 (submitted: July 21, 2021)
  • Describe the humoral immune responses against the B.1.351 and Wuhan-Hu-1 strains induced by 1 dose of AZD1222 in seronegative participants previously vaccinated with AZD1222/SARS-CoV-2 mRNA vaccine [ Time Frame: 28 days post dose ]
    Magnitude of SARS-CoV-2 specific antibody binding and neutralization titres (geometric mean titre) Seroresponse rate of SARS-CoV-2 specific antibody binding and neutralization titres
  • Describe the humoral immune responses against the B.1.351 and Wuhan-Hu-1 strains with 1 dose of AZD1222 followed by 1 dose of AZD2816 administered unvaccinated seronegative participants [ Time Frame: 28 days post second dose ]
    Magnitude of SARS-CoV-2 specific antibody binding and neutralization titres (geometric mean titre) Seroresponse rate of SARS-CoV-2 specific antibody binding and neutralization titres
  • Describe the humoral immune responses against the B.1.351 and Wuhan-Hu-1 strains induced by a 2-dose primary vaccination with AZD1222 in unvaccinated seronegative participants [ Time Frame: 28 days post second dose ]
    Magnitude of SARS-CoV-2 specific antibody binding and neutralization titres (geometric mean titre) Seroresponse rate of SARS-CoV-2 specific antibody binding and neutralization titres
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase II/III Study of AZD2816, for the Prevention of COVID-19 in Adults
Official Title  ICMJE A Phase II/III Partially Double-Blinded, Randomised, Multinational, Active-Controlled Study in Adults to Determine the Safety and Immunogenicity of AZD2816, a Vaccine for the Prevention of COVID-19
Brief Summary The aim of the study is to assess the safety, and immunogenicity of AZD2816 for the prevention of COVID-19
Detailed Description The purpose of this study is to demonstrate the safety and characterize the immunogenicity of AZD2816; AstraZeneca's candidate ChAdOx1 vector vaccine against SARS-CoV-2 variant strain B.1.351
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Previously vaccinated individuals will receive 1 dose of AZD1222 or AZD2816 on Day 1. Previously unvaccinated participants will receive one of the following 2-dose vaccinations:

  • 1 dose of AZD2816 on Day 1 and on Day 29
  • 1 dose of AZD1222 on Day1 and on Day 29
  • 1 dose of AZD1222 on Day 1 and 1 dose of AZD2816 on Day 29
  • 1 dose of AZD2816 on Day 1 and on Day 85. Participants will be followed up for safety for 180 days after last study vaccine administration.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Double Blind: two or more parties are unaware of the intervention assignment.
Primary Purpose: Prevention
Condition  ICMJE
  • COVID-19
  • SARS-CoV-2
Intervention  ICMJE
  • Biological: AZD1222
    10 mM histidine/histidine hydrochloride, 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.
  • Biological: AZD2816
    10 mM histidine/histidine hydrochloride, 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
Study Arms  ICMJE
  • ChAdOx1-S booster: one dose of AZD1222
    Previously vaccinated with AZD1222, dosing on day 1
    Intervention: Biological: AZD1222
  • ChAdOx1-S booster: one dose of AZD2816
    Previously vaccinated with AZD1222, dosing on day 1
    Intervention: Biological: AZD2816
  • mRNA booster: one dose of AZD1222
    Previously vaccinated with an mRNA vaccine, dosing on day 1
    Intervention: Biological: AZD1222
  • mRNA booster: one dose of AZD2816
    Previously vaccinated with an mRNA vaccine, dosing on day 1
    Intervention: Biological: AZD2816
  • 2 doses of AZD1222, 4 weeks apart
    Previously unvaccinated. First dose day 1, second dose day 29
    Intervention: Biological: AZD1222
  • 2 doses of AZD2816, 4 weeks apart
    Previously unvaccinated. First dose day 1, second dose day 29
    Intervention: Biological: AZD2816
  • 2 doses of AZD2816, 12 weeks apart
    Previously unvaccinated. First dose day 1, second dose day 85
    Intervention: Biological: AZD2816
  • one dose of AZD1222 + one dose AZD2816, 4 weeks apart
    Previously unvaccinated. Dose of AZD1222 on day 1, dose of AZD2816 on day 29
    Interventions:
    • Biological: AZD1222
    • Biological: AZD2816
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 5, 2022)		 2848
Original Estimated Enrollment  ICMJE
 (submitted: July 21, 2021)		 2475
Actual Study Completion Date  ICMJE August 2, 2022
Actual Primary Completion Date February 4, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Adult, ≥ 18 years of age at the time of consent

    For inclusion in the SARS-CoV-2 seronegative population:

  2. No history of laboratory-confirmed SARS-CoV-2 infection (ie, no positive nucleic acid amplification test and no positive antibody test).
  3. Seronegative for SARS-CoV-2 at screening (lateral flow test to detect reactivity to the nucleoprotein).
  4. Medically stable such that, according to the judgment of the investigator, hospitalization within the study period is not anticipated and the participant appears likely to be able to remain on study through the end of protocol-specified follow-up
  5. Able to understand and comply with study requirements/procedures (if applicable, with assistance by caregiver, surrogate, or legally authorized representative) based on the assessment of the investigator
  6. Signed informed consent obtained before conducting any study-related procedures

  7. Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

    Previously COVID-19 Vaccinated Participants:

  8. Prior completion of a 2-dose primary homologous vaccination regimen against SARSCoV-2 with either AZD1222 (2 standard doses as authorized vaccine or as investigational product in a clinical trial with a 4 to 12-week dosing interval) or with an mRNA vaccine approved for emergency or conditional use. The second dose in all cases should have been administered at least 3 months prior to first administration of study intervention.

Exclusion Criteria:

  1. History of allergy to any component of AZD1222/AZD2816.
  2. History of Guillain-Barré syndrome, any demyelinating disease, or any other neuroimmunologic condition
  3. Significant infection or other acute illness, including fever > 100 °F (> 37.8 °C) on the day prior to or day of randomization
  4. Any confirmed or suspected immunosuppressive or immunodeficient state, including asplenia or HIV/AIDS.
  5. Recurrent severe infections and use of immunosuppressant medication within the past 6 months (≥ 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 study intervention). The following exceptions are permitted: Topical/inhaled steroids or short-term oral steroids (course lasting ≤ 14 days)
  6. History of primary malignancy (see protocol)
  7. History of thrombocytopenia and/or thrombosis, including participants who have experienced major venous and/or arterial thrombosis in combination with thrombocytopenia following vaccination with any COVID-19 vaccine
  8. History of heparin-induced thrombocytopenia, congenital thrombophilia (ie, factor V Leiden, prothrombin G20210A, antithrombin III deficiency, protein C deficiency and protein S deficiency, factor XIII mutation, familial dysfibrinogenemia), auto-immune thrombophilia (antiphospholipid syndrome, anti-cardiolipin antibodies, anti-β2- glycoprotein 1 antibodies), or paroxysmal nocturnal haemoglobinuria.
  9. Clinically significant bleeding (eg, factor deficiency, coagulopathy, or platelet disorder), or prior history of significant bleeding or bruising following intramuscular injections or venepuncture
  10. Severe and/or uncontrolled cardiovascular disease, respiratory disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, or neurological illness, as judged by the Investigator
  11. Any other significant disease, disorder, or finding that may significantly increase the risk to the participant because of participation in the study, affect the ability of the participant to participate in the study, or impair interpretation of the study data
  12. Any autoimmune conditions, except mild psoriasis and vitiligo.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 115 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Brazil,   Poland,   South Africa,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04973449
Other Study ID Numbers  ICMJE D7220C00001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
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
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (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

URL:

https://astrazenecagroup-dt.pharmacm.com/DT/Home
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home
Current Responsible Party AstraZeneca
Original Responsible Party Same as current
Current Study Sponsor  ICMJE AstraZeneca
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account AstraZeneca
Verification Date January 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP