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

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ClinicalTrials.gov Identifier: NCT04973449
Recruitment Status : Recruiting
First Posted : July 22, 2021
Last Update Posted : September 22, 2021
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
The aim of the study is to assess the safety, and immunogenicity of AZD2816 for the prevention of COVID-19

Condition or disease Intervention/treatment Phase
COVID-19 SARS-CoV-2 Biological: AZD1222 Biological: AZD2816 Phase 2 Phase 3

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 2849 participants
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
Official Title: 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
Actual Study Start Date : June 27, 2021
Estimated Primary Completion Date : October 8, 2021
Estimated Study Completion Date : June 15, 2022

Arm Intervention/treatment
ChAdOx1-S booster: one dose of AZD1222
Previously vaccinated with AZD1222, dosing on day 1
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.

ChAdOx1-S booster: one dose of AZD2816
Previously vaccinated with AZD1222, dosing on day 1
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

mRNA booster: one dose of AZD1222
Previously vaccinated with an mRNA vaccine, dosing on day 1
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.

mRNA booster: one dose of AZD2816
Previously vaccinated with an mRNA vaccine, dosing on day 1
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

2 doses of AZD1222, 4 weeks apart
Previously unvaccinated. First dose day 1, second dose day 29
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.

2 doses of AZD2816, 4 weeks apart
Previously unvaccinated. First dose day 1, second dose day 29
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

2 doses of AZD2816, 12 weeks apart
Previously unvaccinated. First dose day 1, second dose day 85
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

one dose of AZD1222 + one dose AZD2816, 4 weeks apart
Previously unvaccinated. Dose of AZD1222 on day 1, dose of AZD2816 on day 29
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




Primary Outcome Measures :
  1. 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

  2. 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,


  3. The safety and tolerability of a 2-dose primary vaccination with AZD2816 in the naïve unvaccinated cohort [ Time Frame: for 7 days ]
    Incidence of local and systemic solicited AEs

  4. The safety and tolerability of a 2-dose primary vaccination with AZD2816 in the naïve 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


  5. 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

  6. 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 naïve unvaccinated cohort [ Time Frame: 28 days post second dose ]
    GMT ratio of pseudoneutralizing antibodies for AZD2816 vaccination/AZD1222 Vaccination


Secondary Outcome Measures :
  1. 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 naïve unvaccinated cohort [ Time Frame: 28 days post second dose ]
    Difference in seroresponse rates

  2. 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 naive unvaccinated cohort [ Time Frame: 28 days post second dose ]
    GMT ratio of pseudoneutralizing antibodies

  3. 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 naïve unvaccinated cohort [ Time Frame: 28 days post second dose ]
    GMT ratio of pseudoneutralizing antibodies

  4. 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

  5. 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


  6. 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


  7. 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


  8. 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


  9. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 115 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04973449


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
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Brazil
Research Site Recruiting
Brasilia, Brazil, 70200-730
Research Site Recruiting
Curitiba, Brazil, 80810-050
Research Site Recruiting
Natal, Brazil, 59020-035
Research Site Recruiting
Natal, Brazil, 59025-050
Research Site Recruiting
Porto Alegre, Brazil, 90035-903
Research Site Recruiting
Salvador, Brazil, 40110-060
Research Site Not yet recruiting
São Paulo, Brazil, 04037-002
Poland
Research Site Not yet recruiting
Kraków, Poland, 30-348
Research Site Recruiting
Lublin, Poland, 20-362
Research Site Recruiting
Oświęcim, Poland, 32-600
Research Site Recruiting
Puławy, Poland, 24-100
Research Site Not yet recruiting
Skórzewo, Poland, 60-185
Research Site Not yet recruiting
Trzebnica, Poland, 55-100
Research Site Not yet recruiting
Zamosc, Poland, 22-400
South Africa
Research Site Not yet recruiting
Bloemfontein, South Africa, 9301
Research Site Not yet recruiting
Cape Town, South Africa, 7500
Research Site Not yet recruiting
Johannesburg, South Africa, 1818
Research Site Not yet recruiting
Johannesburg, South Africa, 2013
Research Site Not yet recruiting
Johannesburg, South Africa, 2092
Research Site Not yet recruiting
Somerset West, South Africa, 7130
United Kingdom
Research Site Recruiting
Birmingham, United Kingdom, B15 2TH
Research Site Recruiting
Bournemouth, United Kingdom, BH7 7DW
Research Site Recruiting
Bristol, United Kingdom, BS105NB
Research Site Recruiting
Bristol, United Kingdom, BS2 8BJ
Research Site Withdrawn
Dundee, United Kingdom, DD1 9SY
Research Site Recruiting
Edinburgh, United Kingdom, EH16 4SA
Research Site Recruiting
Harrow, United Kingdom, HA1 3UJ
Research Site Recruiting
Hull, United Kingdom, HU3 2KZ
Research Site Recruiting
London, United Kingdom, E2 0HL
Research Site Recruiting
London, United Kingdom, NW1 2BH
Research Site Recruiting
London, United Kingdom, SE1 9RT
Research Site Recruiting
London, United Kingdom, SE5 9NU
Research Site Recruiting
Manchester, United Kingdom, M8 5RB
Research Site Recruiting
Newcastle-upon-Tyne, United Kingdom, NE1 4LP
Research Site Recruiting
Nottingham, United Kingdom, NG7 2QW
Research Site Recruiting
Oxford, United Kingdom, OX3 7EJ
Research Site Recruiting
Plymouth, United Kingdom, PL6 8DH
Research Site Recruiting
Portsmouth, United Kingdom, PO1 3HN
Research Site Recruiting
Sheffield, United Kingdom, S5 7AU
Research Site Recruiting
Truro, United Kingdom, TR1 3LJ
Sponsors and Collaborators
AstraZeneca
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04973449    
Other Study ID Numbers: D7220C00001
First Posted: July 22, 2021    Key Record Dates
Last Update Posted: September 22, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
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
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

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
COVID-19 Vaccine
Additional relevant MeSH terms:
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COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases