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

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

Detailed Description
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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

Official Title
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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

Conditions
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COVID-19, SARS-CoV-2

Intervention / Treatment
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* Biological: AZD1222
* Biological: AZD2816


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult, ≥ 18 years of age at the time of consent For inclusion in the SARS-CoV-2 seronegative population: 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. Exclusion Criteria: 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 HIV/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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 115 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: ChAdOx1-S booster: one dose of AZD1222<br>Previously vaccinated with AZD1222, dosing on day 1 | Biological: AZD1222<br>* 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.<br>|
| Other: ChAdOx1-S booster: one dose of AZD2816<br>Previously vaccinated with AZD1222, dosing on day 1 | Biological: AZD2816<br>* 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<br>|
| Other: mRNA booster: one dose of AZD1222<br>Previously vaccinated with an mRNA vaccine, dosing on day 1 | Biological: AZD1222<br>* 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.<br>|
| Other: mRNA booster: one dose of AZD2816<br>Previously vaccinated with an mRNA vaccine, dosing on day 1 | Biological: AZD2816<br>* 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<br>|
| Other: 2 doses of AZD1222, 4 weeks apart<br>Previously unvaccinated. First dose day 1, second dose day 29 | Biological: AZD1222<br>* 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.<br>|
| Other: 2 doses of AZD2816, 4 weeks apart<br>Previously unvaccinated. First dose day 1, second dose day 29 | Biological: AZD2816<br>* 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<br>|
| Other: 2 doses of AZD2816, 12 weeks apart<br>Previously unvaccinated. First dose day 1, second dose day 85 | Biological: AZD2816<br>* 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<br>|
| Other: one dose of AZD1222 + one dose AZD2816, 4 weeks apart<br>Previously unvaccinated. Dose of AZD1222 on day 1, dose of AZD2816 on day 29 | Biological: AZD1222<br>* 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.<br>Biological: AZD2816<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19 Vaccine