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

• Sponsor: AstraZeneca (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT04973449
• Collaborator: (none)
• Enrollment: 2,848
• Locations: 35
• Arms: 8
• Anticipated Duration (Months): 13.2
• Patients Per Site: 81.4
• Patients Per Site Per Month: 6.2

Study Details

Study Description

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 2848 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.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: Jun 27, 2021
• Actual Primary Completion Date: Jan 21, 2022
• Anticipated Study Completion Date: Aug 3, 2022

Arms and Interventions

Arm	Intervention/Treatment
Other: 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.
Other: 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
Other: 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.
Other: 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
Other: 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.
Other: 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
Other: 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
Other: 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

Outcome Measures

Primary Outcome Measures

1. The safety and tolerability of 1 dose of AZD2816 in the previously vaccinated cohort with AZD1222 [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 [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 unvaccinated cohort [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 unvaccinated cohort [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 [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 unvaccinated cohort [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 unvaccinated cohort [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 unvaccinated cohort [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 unvaccinated cohort [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 [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 [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 [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 [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 [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 [28 days post second dose]

   GMT ratio of pseudoneutralizing antibodies

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 115 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Adult, ≥ 18 years of age at the time of consent

For inclusion in the SARS-CoV-2 seronegative population:

1. No history of laboratory-confirmed SARS-CoV-2 infection (ie, no positive nucleic acid amplification test and no positive antibody test).

2. Seronegative for SARS-CoV-2 at screening (lateral flow test to detect reactivity to the nucleoprotein).

3. 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

4. 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

5. Signed informed consent obtained before conducting any study-related procedures

6. 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:

1. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Brasilia		Brazil	70200-730
2	Research Site	Curitiba		Brazil	80810-050
3	Research Site	Natal		Brazil	59020-035
4	Research Site	Natal		Brazil	59025-050
5	Research Site	Porto Alegre		Brazil	90035-903
6	Research Site	Salvador		Brazil	40110-060
7	Research Site	Lublin		Poland	20-362
8	Research Site	Oświęcim		Poland	32-600
9	Research Site	Puławy		Poland	24-100
10	Research Site	Zamosc		Poland	22-400
11	Research Site	Bloemfontein		South Africa	9301
12	Research Site	Cape Town		South Africa	7500
13	Research Site	Johannesburg		South Africa	1818
14	Research Site	Johannesburg		South Africa	2013
15	Research Site	Johannesburg		South Africa	2092
16	Research Site	Somerset West		South Africa	7130
17	Research Site	Birmingham		United Kingdom	B15 2TH
18	Research Site	Bournemouth		United Kingdom	BH7 7DW
19	Research Site	Bristol		United Kingdom	BS105NB
20	Research Site	Bristol		United Kingdom	BS2 8BJ
21	Research Site	Edinburgh		United Kingdom	EH16 4SA
22	Research Site	Harrow		United Kingdom	HA1 3UJ
23	Research Site	Hull		United Kingdom	HU3 2KZ
24	Research Site	London		United Kingdom	E2 0HL
25	Research Site	London		United Kingdom	NW1 2BH
26	Research Site	London		United Kingdom	SE1 9RT
27	Research Site	London		United Kingdom	SE5 9NU
28	Research Site	Manchester		United Kingdom	M8 5RB
29	Research Site	Newcastle-upon-Tyne		United Kingdom	NE1 4LP
30	Research Site	Nottingham		United Kingdom	NG7 2QW
31	Research Site	Oxford		United Kingdom	OX3 7EJ
32	Research Site	Plymouth		United Kingdom	PL6 8DH
33	Research Site	Portsmouth		United Kingdom	PO1 3HN
34	Research Site	Sheffield		United Kingdom	S5 7AU
35	Research Site	Truro		United Kingdom	TR1 3LJ

Sponsors and Collaborators

• AstraZeneca

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT04973449
• Other Study ID Numbers: D7220C00001
• First Posted: Jul 22, 2021
• Last Update Posted: Jun 28, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• 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: COVID-19

Study Results

No Results Posted as of Jun 28, 2022