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

NCT04973449 | Completed Phase 2 Results DMC

• 2 other identifiers: D7220C000012021-002530-17
• Study Type: interventional
• Target: 2,843
• Locations: 4 countries
• Sites: 35

Brief Summary

The aim of the study is to assess the safety, and immunogenicity of AZD2816 for the prevention of coronavirus disease 2019 (COVID-19).

Conditions

COVID-19; SARS-CoV-2

Keywords

COVID-19 Vaccine

Outcome Measures

Primary Outcomes (7)

• Number of Participants With Local and Systemic Solicited Treatment Emergent Adverse Events (TEAEs) in Primary Vaccination Cohort (PVC):- AZD2816 (4), Booster Cohorts:-AZD1222:AZD2816, and mRNA:AZD2816

  An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. Solicited AEs are local or systemic predefined events for assessment of reactogenicity. An e-diary was used to collect information on the timing and severity of the solicited AEs. Local AEs included pain, redness/erythema, tenderness, induration/swelling at the site of the injection. Systemic AEs included fever (\> 100 °F/37.8 °C), chills, muscle pains, fatigue, headache, malaise, nausea, and vomiting.

  During the 7-day follow-up period after vaccination (vaccines administered on Days 1 and 29 [only for primary vaccination cohort])

• Number of Participants With Unsolicited TEAEs, Treatment-emergent Serious AEs (TESAEs), Medically Attended AEs (MAAEs), and Adverse Events of Special Interest (AESIs) in PVC:- AZD2816 (4), Booster Cohorts:- AZD1222:AZD2816, and mRNA:AZD2816

  The AEs other than solicited AEs are reported as unsolicited AEs and were collected by "open question" at study visits. AE: any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. TEAEs: events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. SAE: an AE resulting in any of following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience; persistent or significant disability/incapacity; congenital anomaly. MAAE: an AE leading to a non-routine/unscheduled medically-attended visit, to or from medical doctor for any reason. AESI: an event of scientific and medical interest specific to further understanding of study drug safety profile and require close monitoring and rapid communication by investigators to Sponsor.

  During the 28-day follow-up period after vaccination (vaccines administered on Days 1 and 29 [only for primary vaccination cohort])

• Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs in Primary Vaccination Cohort:- AZD2816 (4), Booster Cohorts:-AZD1222:AZD2816 and mRNA:AZD2816

  Number of participants with abnormal laboratory parameters reported as TEAEs are reported. Laboratory tests included haematology and clinical chemistry.

  During the 28-day follow-up period after vaccination (vaccines administered on Days 1 and 29 [only for primary vaccination cohort])

• Geometric Mean Titre (GMT) of SARS-CoV-2 Neutralizing Antibodies (nAb) Against B.1.351 Variant Elicited by Primary Vaccination Cohort:- AZD2816 (4) and the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD1222 (4)

  Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Primary Vaccination Cohort:- AZD2816 (4) with response against B.1.351 variant is the comparator group and Primary Vaccination Cohort:- AZD1222 (4) with response against the original Wuhan-Hu-1 strain is the reference group.

  28 days after second dose (Day 57)

• GMT of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- AZD1222:AZD1222 and AZD1222 in Historical Control

  Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Booster Cohort:- AZD1222:AZD1222 is the comparator group and AZD1222 in Historical Control is the reference group, both compared for response against the original Wuhan-Hu-1 strain.

  Booster Cohort: 28 days after booster dose (Day 29) and Historical Control: 28 days after the second dose (Day 57)

• Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against the B.1.351 Variant Elicited by Primary Vaccination Cohort:- AZD2816 (4) and the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD1222 (4)

  Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as \>= 4-fold increase in the GMT of nAb from baseline. Primary Vaccination Cohort:- AZD2816 (4) with response against B.1.351 variant is the comparator group and Primary Vaccination Cohort:- AZD1222 (4) with response against the original Wuhan-Hu-1 strain is the reference group.

  28 days after second dose (Day 57)

• GMT of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- mRNA:AZD1222 and AZD1222 in Historical Control

  Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Booster Cohort:- mRNA:AZD1222 is the comparator group and AZD1222 in Historical Control is the reference group, both compared for response against the original Wuhan-Hu-1 strain.

  Booster Cohort: 28 days after booster dose (Day 29) and Historical Control: 28 days after the second dose (Day 57)

Secondary Outcomes (64)

• Number of Participants With Local and Systemic Solicited TEAEs

  During the 7-day follow-up period after vaccination (vaccines administered on Days 1 and 29 or Day 85 [only for primary vaccination cohorts])

• Number of Participants With Unsolicited TEAEs, TESAEs, MAAEs, and AESIs

  During the 28-day follow-up period after vaccination (vaccines administered on Days 1 and 29 or Day 85 [only for primary vaccination cohorts])

• GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Primary Vaccination Cohort:- AZD2816 (4) and Primary Vaccination Cohort:- AZD1222 (4)

  28 days after second dose (Day 57)

• GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) and the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD1222 (4)

  28 days after second dose (Day 57)

• GMT of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD2816 (4) and Primary Vaccination Cohort:- AZD1222 (4)

  28 days after second dose (Day 57)

Study Arms (8)

Primary Vaccination Cohort:- AZD1222 (4)

EXPERIMENTAL

Previously unvaccinated participants received intramuscular (IM) AZD1222 5\*10\^10 viral particles (vp) on Days 1 and 29 (4-week dosing interval).

Biological: AZD1222

Primary Vaccination Cohort:- AZD2816 (4)

EXPERIMENTAL

Previously unvaccinated participants received IM AZD2816 5\*10\^10 vp on Days 1 and 29 (4-week dosing interval).

Biological: AZD2816

Primary Vaccination Cohort:- AZD1222 + AZD2816 (4)

EXPERIMENTAL

Previously unvaccinated participants received IM AZD1222 5\*10\^10 vp on Day 1 and IM AZD2816 5\*10\^10 vp on Day 29 (4-week dosing interval).

Biological: AZD1222; Biological: AZD2816

Primary Vaccination Cohort:- AZD2816 (12)

EXPERIMENTAL

Previously unvaccinated participants received IM AZD2816 5\*10\^10 vp on Days 1 and 85 (12-week dosing interval).

Biological: AZD2816

Booster Cohort:- AZD1222:AZD1222

EXPERIMENTAL

Participants, who previously received 2 doses of AZD1222 vaccine according to the authorized dose and dosing regimen, with second dose administered at least 90 days prior to study treatment, received booster dose of IM AZD1222 5\*10\^10 vp on Day 1.

Biological: AZD1222

Booster Cohort:- AZD1222:AZD2816

EXPERIMENTAL

Participants, who previously received 2 doses of AZD1222 vaccine according to the authorized dose and dosing regimen, with second dose administered at least 90 days prior to study treatment, received booster dose of IM AZD2816 5\*10\^10 vp on Day 1.

Biological: AZD2816

Booster Cohort:- mRNA:AZD1222

EXPERIMENTAL

Participants, who previously received 2 doses of approved mRNA based vaccine according to the authorized dose and dosing regimen, with second dose administered at least 90 days prior to study treatment, received booster dose of IM AZD1222 5\*10\^10 vp on Day 1.

Biological: AZD1222

Booster Cohort:- mRNA:AZD2816

EXPERIMENTAL

Participants, who previously received 2 doses of approved mRNA based vaccine according to the authorized dose and dosing regimen, with second dose administered at least 90 days prior to study treatment, received booster dose of IM AZD2816 5\*10\^10 vp on Day 1.

Biological: AZD2816

Interventions

AZD1222 BIOLOGICAL

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.

Booster Cohort:- AZD1222:AZD1222; Booster Cohort:- mRNA:AZD1222; Primary Vaccination Cohort:- AZD1222 (4); Primary Vaccination Cohort:- AZD1222 + AZD2816 (4)

AZD2816 BIOLOGICAL

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.

Booster Cohort:- AZD1222:AZD2816; Booster Cohort:- mRNA:AZD2816; Primary Vaccination Cohort:- AZD1222 + AZD2816 (4); Primary Vaccination Cohort:- AZD2816 (12); Primary Vaccination Cohort:- AZD2816 (4)

Eligibility Criteria

• Age: 18 Years - 115 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult, ≥ 18 years of age at the time of consent.
• No history of laboratory-confirmed SARS-CoV-2 infection (ie, no positive nucleic acid amplification test and no positive antibody test).
• Seronegative for SARS-CoV-2 at screening (lateral flow test to detect reactivity to the nucleoprotein).
• 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.
• 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.
• Signed informed consent obtained before conducting any study-related procedures.
• 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:
• 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.

You may not qualify if:

• History of allergy to any component of AZD1222/AZD2816.
• History of Guillain-Barré syndrome, any demyelinating disease, or any other neuroimmunologic condition.
• Significant infection or other acute illness, including fever \> 100 °F (\> 37.8 °C) on the day prior to or day of randomization.
• Any confirmed or suspected immunosuppressive or immunodeficient state, including asplenia or human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS).
• 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).
• History of primary malignancy (see protocol).
• 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.
• 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.
• Clinically significant bleeding (eg, factor deficiency, coagulopathy, or platelet disorder), or prior history of significant bleeding or bruising following intramuscular injections or venepuncture.
• Severe and/or uncontrolled cardiovascular disease, respiratory disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, or neurological illness, as judged by the Investigator.
• 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.
• Any autoimmune conditions, except mild psoriasis and vitiligo.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (35)

Research Site

Brasília, 70200-730, Brazil

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Curitiba, 80810-050, Brazil

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Natal, 59020-035, Brazil

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Natal, 59025-050, Brazil

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Porto Alegre, 90035-903, Brazil

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Salvador, 40110-060, Brazil

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Lublin, 20-362, Poland

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Oświęcim, 32-600, Poland

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Puławy, 24-100, Poland

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Zamość, 22-400, Poland

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Bloemfontein, 9301, South Africa

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Cape Town, 7500, South Africa

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Johannesburg, 1818, South Africa

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Johannesburg, 2013, South Africa

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Johannesburg, 2092, South Africa

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Somerset West, 7130, South Africa

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Birmingham, B15 2TH, United Kingdom

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Bournemouth, BH7 7DW, United Kingdom

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Bristol, BS105NB, United Kingdom

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Bristol, BS2 8BJ, United Kingdom

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Edinburgh, EH16 4SA, United Kingdom

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Harrow, HA1 3UJ, United Kingdom

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Hull, HU3 2KZ, United Kingdom

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London, E2 0HL, United Kingdom

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London, NW1 2BH, United Kingdom

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London, SE1 9RT, United Kingdom

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London, SE5 9NU, United Kingdom

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Manchester, M8 5RB, United Kingdom

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Newcastle upon Tyne, NE1 4LP, United Kingdom

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Nottingham, NG7 2QW, United Kingdom

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Oxford, OX3 7EJ, United Kingdom

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Plymouth, PL6 8DH, United Kingdom

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Portsmouth, PO1 3HN, United Kingdom

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Sheffield, S5 7AU, United Kingdom

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Truro, TR1 3LJ, United Kingdom

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Related Publications (2)

• Costa Clemens SA, Jepson B, Bhorat QE, Ahmad A, Akhund T, Aley PK, Bansal H, Bibi S, Kelly EJ, Khan M, Lambe T, Lombaard JJ, Matthews S, Pipolo Milan E, Olsson U, Ramasamy MN, Moura de Oliveira Paiva MS, Seegobin S, Shoemaker K, Szylak A, Villafana T, Pollard AJ, Green JA; AZD2816 Study Group. Immunogenicity and safety of beta variant COVID-19 vaccine AZD2816 and AZD1222 (ChAdOx1 nCoV-19) as primary-series vaccination for previously unvaccinated adults in Brazil, South Africa, Poland, and the UK: a randomised, partly double-blinded, phase 2/3 non-inferiority immunobridging study. Lancet Microbe. 2024 Aug;5(8):100863. doi: 10.1016/S2666-5247(24)00078-8. Epub 2024 Jun 12.

  PMID: 38878794 DERIVED

• Ramasamy MN, Kelly EJ, Seegobin S, Dargan PI, Payne R, Libri V, Adam M, Aley PK, Martinez-Alier N, Church A, Jepson B, Khan M, Matthews S, Townsend GT, Vekemans J, Bibi S, Swanson PA 2nd, Lambe T, Pangalos MN, Villafana T, Pollard AJ, Green JA; AZD2816 Study Group. Immunogenicity and safety of AZD2816, a beta (B.1.351) variant COVID-19 vaccine, and AZD1222 (ChAdOx1 nCoV-19) as third-dose boosters for previously vaccinated adults: a multicentre, randomised, partly double-blinded, phase 2/3 non-inferiority immunobridging study in the UK and Poland. Lancet Microbe. 2023 Nov;4(11):e863-e874. doi: 10.1016/S2666-5247(23)00177-5. Epub 2023 Sep 29.

  PMID: 37783221 DERIVED

Related Links

• Related Info
• Clinical Study Protocol
• 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

Since different assays were used between strains and also within the same strains between this study and historical control study D8110C00001 (NCT04516746), spike protein binding antibody results were summarised descriptively; no comparative analyses were conducted.

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca Clinical study Information Center

information.center@astrazeneca.com

+1-877-240-9479

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double Blind: two or more parties are unaware of the intervention assignment.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 2, 2021
• First Posted: July 22, 2021
• Study Start: June 27, 2021
• Primary Completion: February 4, 2022
• Study Completion: August 2, 2022
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-04

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 URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

Locations

PL (4); GB (19); ZA (6); BR (6)