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

AstraZeneca

Status and phase: Completed; Phase 3; Phase 2

Conditions: COVID-19; SARS-CoV-2

Treatments: Biological: AZD1222; Biological: AZD2816

Study type: Interventional

Funder types: Industry

Identifiers

NCT04973449

D7220C00001

2021-002530-17 (EudraCT Number)

Details and patient eligibility

About

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

Full description

The purpose of this study is to demonstrate the safety and characterize the immunogenicity of AZD2816; AstraZeneca's candidate chimpanzee adenovirus Ox1 (ChAdOx1) vector vaccine against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) variant strain B.1.351.

Enrollment: 2,843 patients

Sex: All

Ages: 18 to 115 years old

Volunteers: Accepts Healthy Volunteers

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 human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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2,843 participants in 8 patient groups

Primary Vaccination Cohort:- AZD1222 (4)

Experimental group

Description:

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

Treatment:

Biological: AZD1222

Primary Vaccination Cohort:- AZD2816 (4)

Experimental group

Description:

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

Treatment:

Biological: AZD2816

Primary Vaccination Cohort:- AZD1222 + AZD2816 (4)

Experimental group

Description:

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).

Treatment:

Biological: AZD2816

Biological: AZD1222

Primary Vaccination Cohort:- AZD2816 (12)

Experimental group

Description:

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

Treatment:

Biological: AZD2816

Booster Cohort:- AZD1222:AZD1222

Experimental group

Description:

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.

Treatment:

Biological: AZD1222

Booster Cohort:- AZD1222:AZD2816

Experimental group

Description:

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.

Treatment:

Biological: AZD2816

Booster Cohort:- mRNA:AZD1222

Experimental group

Description:

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.

Treatment:

Biological: AZD1222

Booster Cohort:- mRNA:AZD2816

Experimental group

Description:

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.

Treatment:

Biological: AZD2816