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

COVID-19 Clinical Trial

— AZD2816  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04973449
• Other study ID #: D7220C00001
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: June 27, 2021
• Est. completion date: August 2, 2022

Study information

• Verified date: January 2023
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2848
• Est. completion date: August 2, 2022
• Est. primary completion date: February 4, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 115 Years

Eligibility

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-ß2- 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.

Related Conditions & MeSH terms

• COVID-19
• SARS-CoV-2

Intervention

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.
• 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

Locations

Country	Name	City	State
Brazil	Research Site	Brasilia
Brazil	Research Site	Curitiba
Brazil	Research Site	Natal
Brazil	Research Site	Natal
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Salvador
Poland	Research Site	Lublin
Poland	Research Site	Oswiecim
Poland	Research Site	Pulawy
Poland	Research Site	Zamosc
South Africa	Research Site	Bloemfontein
South Africa	Research Site	Cape Town
South Africa	Research Site	Johannesburg
South Africa	Research Site	Johannesburg
South Africa	Research Site	Johannesburg
South Africa	Research Site	Somerset West
United Kingdom	Research Site	Birmingham
United Kingdom	Research Site	Bournemouth
United Kingdom	Research Site	Bristol
United Kingdom	Research Site	Bristol
United Kingdom	Research Site	Edinburgh
United Kingdom	Research Site	Harrow
United Kingdom	Research Site	Hull
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Newcastle-upon-Tyne
United Kingdom	Research Site	Nottingham
United Kingdom	Research Site	Oxford
United Kingdom	Research Site	Plymouth
United Kingdom	Research Site	Portsmouth
United Kingdom	Research Site	Sheffield
United Kingdom	Research Site	Truro

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

Brazil,  Poland,  South Africa,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The safety and tolerability of 1 dose of AZD2816 in the previously vaccinated cohort with AZD1222	Incidence of local and systemic solicited AEs	for 7 days
Primary	The safety and tolerability of 1 dose of AZD2816 in the previously vaccinated cohort with AZD1222	The change from baseline for safety laboratory measures; Incidence of unsolicited AEs, including MAAEs, SAEs, and AESIs,	28 days post dose
Primary	The safety and tolerability of a 2-dose primary vaccination with AZD2816 in the unvaccinated cohort	Incidence of local and systemic solicited AEs	for 7 days
Primary	The safety and tolerability of a 2-dose primary vaccination with AZD2816 in the unvaccinated cohort	The change from baseline for safety laboratory measures; Incidence of unsolicited AEs, including MAAEs, SAEs, and AESIs	28 days post dose
Primary	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	GMT ratio of pseudoneutralizing antibodies for AZD2816 booster/AZD1222 vaccination	28 days post second dose
Primary	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	GMT ratio of pseudoneutralizing antibodies for AZD2816 vaccination/AZD1222 Vaccination	28 days post second dose
Secondary	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	Difference in seroresponse rates	28 days post second dose
Secondary	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	GMT ratio of pseudoneutralizing antibodies	28 days post second dose
Secondary	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	GMT ratio of pseudoneutralizing antibodies	28 days post second dose
Secondary	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	GMT ratio of pseudoneutralizing antibodies	28 days post second dose
Secondary	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	GMT ratio of pseudoneutralizing antibodies; Difference in seroresponse rates	28 days post second dose
Secondary	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	GMT ratio of pseudoneutralizing antibodies; Difference in seroresponse rates	28 days post second dose
Secondary	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	GMT ratio of pseudoneutralizing antibodies; Difference in seroresponse rates	28 days post second dose
Secondary	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	GMT ratio of pseudoneutralizing antibodies; Difference in seroresponse rates	28 days post second dose
Secondary	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	GMT ratio of pseudoneutralizing antibodies	28 days post second dose