A Phase II/III Partially Double-Blinded, Randomised, Multinational, Active-Controlled Study in Both Previously Vaccinated and Unvaccinated Adults to Determine the Safety and Immunogenicity of AZD2816, a Vaccine for the Prevention of COVID-19 Caused by Variant Strains of SARS-CoV-2

Start Date14 Jul 2021

Sponsor / Collaborator

AstraZeneca AB

NCT04973449 / CompletedPhase 2/3

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

Start Date27 Jun 2021

Sponsor / Collaborator

AstraZeneca PLC

100 Clinical Results associated with AZD-2816

100 Translational Medicine associated with AZD-2816

100 Patents (Medical) associated with AZD-2816

Literatures (Medical) associated with AZD-2816

01 Aug 2024·Lancet Microbe

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

Article

Author: Lombaard, Johan J ; Shoemaker, Kathryn ; Lambe, Teresa ; Bhorat, Qasim E ; Akhund, Tauseefullah ; Bibi, Sagida ; Ramasamy, Maheshi N ; Matthews, Sam ; Moura de Oliveira Paiva, Maria Sanali ; Szylak, Ameena ; Pipolo Milan, Eveline ; Bansal, Himanshu ; Khan, Mark ; Aley, Parvinder K ; Kelly, Elizabeth J ; Ahmad, Abdullahi ; Pollard, Andrew J ; Villafana, Tonya ; Olsson, Urban ; Seegobin, Seth ; Costa Clemens, Sue Ann ; Jepson, Brett ; Green, Justin A

BACKGROUND:

AZD2816 is a variant-adapted COVID-19 vaccine that expresses the full-length SARS-CoV-2 beta variant spike protein but is otherwise similar to AZD1222 (ChAdOx1 nCoV-19). This study aimed to evaluate the safety and immunogenicity of AZD1222 or AZD2816 (or both) primary-series vaccination in a cohort of adult participants who were previously unvaccinated.

METHODS:

In this phase 2/3, randomised, multinational, active-controlled, non-inferiority, immunobridging study, adult participants previously unvaccinated for COVID-19 were enrolled at 16 study sites in Brazil, South Africa, Poland, and the UK. Participants were stratified by age, sex, and comorbidity and randomly assigned 5:5:5:2 to receive a primary series of AZD1222 (AZD1222 group), AZD2816 (AZD2816 [4-week] group), or AZD1222-AZD2816 (AZD1222-AZD2816 group) at 4-week dosing intervals, or AZD2816 at a 12-week interval (AZD2816 [12-week] group) and evaluated for safety and immunogenicity through 180 days after dose 2. Primary outcomes were safety (rates of solicited adverse events occurring during 7 days and unsolicited adverse events occurring during 28 days after each dose) and immunogenicity (non-inferiority of pseudovirus neutralising antibody geometric mean titre [GMT], GMT ratio margin of 0·67, and seroresponse rate, rate difference margin of -10%, recorded 28 days after dose 2 with AZD2816 [4-week interval] against beta vs AZD1222 against ancestral SARS-CoV-2) in participants who were seronegative at baseline. This trial is registered with ClinicalTrials.gov, NCT04973449, and is completed.

FINDINGS:

Between July 7 and Nov 12, 2021, 1449 participants were assigned to the AZD1222 group (n=413), the AZD2816 (4-week) group (n=415), the AZD1222-AZD2816 group (n=412), and the AZD2816 (12-week) group (n=209). Ten (2·6%) of 378 participants who were seronegative at baseline in the AZD1222 group, nine (2·4%) of 379 in the AZD2816 (4-week) group, eight (2·1%) of 380 in the AZD1222-AZD2816 group, and 11 (5·8%) of 191 in the AZD2816 (12-week) group had vaccine-related unsolicited adverse events. Serious adverse events were recorded in one (0·3%) participant in the AZD1222 group, one (0·3%) in the AZD2816 (4-week) group, two (0·5%) in the AZD1222-AZD2816 group, and none in the AZD2816 (12-week) group. Co-primary immunogenicity endpoints were met: neutralising antibody GMT (ratio 1·19 [95% CI 1·08-1·32]; lower bound greater than 0·67) and seroresponse rate (difference 1·7% [-3·1 to 6·5]; lower bound greater than -10%) at 28 days after dose 2 were non-inferior in the AZD2816 (4-week) group against beta versus in the AZD1222 group against ancestral SARS-CoV-2. Seroresponse rates were highest with AZD2816 against beta (12-week interval 94·3% [95% CI 89·4-97·3]; 4-week interval 85·7% [81·5-89·2]) and with AZD1222 (84·6% [80·3-88·2]) against ancestral SARS-CoV-2.

INTERPRETATION:

Primary series of AZD1222 and AZD2816 were well tolerated, with no emergent safety concerns. Both vaccines elicited robust immunogenicity against beta and ancestral SARS-CoV-2 with greater responses demonstrated when testing against SARS-CoV-2 strains that matched those targeted by the respective vaccine. These findings demonstrate the continued importance of ancestral COVID-19 vaccines in protecting against severe COVID-19 and highlight the feasibility of using the ChAdOx1 platform to develop COVID-19 vaccines against future SARS-CoV-2 variants.

FUNDING:

AstraZeneca.

01 Nov 2023·The Lancet. Microbe

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

Article

Author: Moran, Ed ; Bisnauthsing, Karen ; Pangalos, Menelas N ; Konieczny, Marek ; Padilla, Marcelino Giune ; Lambe, Teresa ; Ramasamy, Maheshi N ; Nagra, Deepak ; Ustianowski, Andrew ; Jepson, Brett ; Desai, Amisha ; Pollard, Andrew J ; Seegobin, Seth ; Libri, Vincenzo ; Turner, David ; Rampling, Tommy ; Adam, Matthew ; Dargan, Paul I ; Aksyuk, Anastasia ; Khan, Mark ; Whittington, Ashley ; Lazarus, Rajeka ; Morris, Sheila ; Roe, Tiffany ; Kobielusz Gembala, Iwona ; Moore, Patrick ; Wildman, Eden ; Aley, Parvinder K ; Royal, Simon ; Villafana, Tonya ; Smith, Catherine ; Church, Alison ; Colton, Hayley ; Kelly, Elizabeth J ; Townsend, G Todd ; Vekemans, Johan ; Galloway, James ; Wrin, Terri ; Bibi, Sagida ; Hunter, Ewan ; Sahdev, Anju ; Green, Christopher ; Payne, Ruth ; Petropoulos, Christos J ; Leeman, Lucy ; Uriel, Alison ; Martinez-Alier, Nuria ; Matthews, Sam ; Swanson, Phillip A ; Shoemaker, Kathryn ; Penciu, Florentina ; Lakeman, Nicki ; Green, Justin A

BACKGROUND:

This study aimed to evaluate AZD2816, a variant-updated COVID-19 vaccine expressing the full-length SARS-CoV-2 beta (B.1.351) variant spike protein that is otherwise similar to AZD1222 (ChAdOx1 nCoV-19), and AZD1222 as third-dose boosters.

METHODS:

This phase 2/3, partly double-blinded, randomised, active-controlled study was done at 19 sites in the UK and four in Poland. Adult participants who had received a two-dose AZD1222 or mRNA vaccine primary series were randomly assigned by means of an Interactive Response Technology-Randomisation and Trial Supply Management system (1:1 within each primary-series cohort, stratified by age, sex, and comorbidities) to receive AZD1222 or AZD2816 (intramuscular injection; 5 × 10¹⁰ viral particles). Participants, investigators, and all sponsor staff members involved in study conduct were masked to randomisation. AZD1222 and AZD2816 doses were prepared by unmasked study staff members. The primary objectives were to evaluate safety and humoral immunogenicity (non-inferiority of day-29 pseudovirus neutralising antibody geometric mean titre [GMT] against ancestral SARS-CoV-2: AZD1222 booster vs AZD1222 primary series [historical controls]; margin 0·67; SARS-CoV-2-seronegative participants). This study is registered with ClinicalTrials.gov, NCT04973449, and is completed.

FINDINGS:

Between June 27 and Sept 30, 2021, 1394 participants of the 1741 screened were randomly assigned to AZD1222 or AZD2816 following an AZD1222 (n=373, n=377) or mRNA vaccine (n=322, n=322) primary series. In SARS-CoV-2-seronegative participants receiving AZD1222 or AZD2816, 78% and 80% (AZD1222 primary series) and 90% and 93%, respectively (mRNA vaccine primary series) reported solicited adverse events to the end of day 8; 2%, 2%, 1%, and 1% had serious adverse events and 12%, 12%, 10%, and 11% had adverse events of special interest, respectively, to the end of day 180. The primary immunogenicity non-inferiority endpoint was met: day-29 neutralising antibody GMT ratios (ancestral SARS-CoV-2) were 1·02 (95% CI 0·90-1·14) and 3·47 (3·09-3·89) with AZD1222 booster versus historical controls (AZD1222 and mRNA vaccine primary series, respectively). Responses against beta were greater with AZD2816 versus AZD1222 (GMT ratios, AZD1222, mRNA vaccine primary series 1·84 [1·63-2·08], 2·22 [1·99-2·47]).

INTERPRETATION:

Both boosters were well tolerated, with immunogenicity against ancestral SARS-CoV-2 similar to AZD1222 primary-series vaccination. AZD2816 gave greater immune responses against beta versus AZD1222.

FUNDING:

AstraZeneca.

01 Mar 2022·EBioMedicineQ1 · MEDICINE

The ChAdOx1 vectored vaccine, AZD2816, induces strong immunogenicity against SARS-CoV-2 beta (B.1.351) and other variants of concern in preclinical studies

Q1 · MEDICINE

ArticleOA

Author: Kailath, Reshma ; Truby, Adam ; Bailey, Dalan ; McTamney, Patrick ; Davies, Hannah ; Ren, Kuishu ; Bissett, Cameron ; Rudiansyah, Indra ; Ulaszewska, Marta ; Dejnirattisai, Wanwisa ; Gilbert, Sarah C ; Newman, Joseph ; Thakur, Nazia ; Screaton, Gavin ; Lambe, Teresa ; Powers, Claire ; Donnellan, Francesca R ; Spencer, Alexandra J ; Bright, Helen ; Morris, Susan ; Liu, Chang ; Allen, Elizabeth R ; Mongkolsapaya, Juthathip ; Peacock, Thomas P ; Barclay, Wendy S ; Pulido, David

BACKGROUND:

There is an ongoing global effort to design, manufacture, and clinically assess vaccines against SARS-CoV-2. Over the course of the ongoing pandemic a number of new SARS-CoV-2 virus isolates or variants of concern (VoC) have been identified containing mutations in key proteins.

METHODS:

In this study we describe the generation and preclinical assessment of a ChAdOx1-vectored vaccine (AZD2816) which expresses the spike protein of the Beta VoC (B.1.351).

FINDINGS:

We demonstrate that AZD2816 is immunogenic after a single dose. When AZD2816 is used as a booster dose in animals primed with a vaccine encoding the original spike protein (ChAdOx1 nCoV-19/ [AZD1222]), an increase in binding and neutralising antibodies against Beta (B.1.351), Gamma (P.1) and Delta (B.1.617.2) is observed following each additional dose. In addition, a strong and polyfunctional T cell response was measured all booster regimens.

INTERPRETATION:

Real world data is demonstrating that one or more doses of licensed SARS-CoV-2 vaccines confer reduced protection against hospitalisation and deaths caused by divergent VoC, including Omicron. Our data support the ongoing clinical development and testing of booster vaccines to increase immunity against highly mutated VoC.

FUNDING:

This research was funded by AstraZeneca with supporting funds from MRC and BBSRC.

News (Medical) associated with AZD-2816

19 Oct 2022

·www.pmlive.com

New study identifies gene associated with strong immune response to COVID-19 vaccines

A gene associated with a higher immune response and protection after vaccination against COVID-19 has been identified by researchers at the University of Oxford. The research provides some of the first evidence of a relationship between genetic factors and the way that people’s immune systems respond to COVID-19 vaccines. In the study, which was published in Nature Medicine , the researchers found that those carrying a version of an HLA gene called HLA-DQB1*06 generated a higher antibody response than those who did not. The HLA gene helps the immune system distinguish the body's own proteins from foreign ones, such as those made by viruses and bacteria. The researchers also found that those carrying this gene, present in two out of every five people in the UK, were less likely to experience COVID-19 infection following vaccination compared to those who did not have it. “From this study we have evidence that our genetic makeup is one of the reasons why we may differ from each other in our immune response following COVID-19 vaccination. We found that inheriting a specific variant of an HLA gene was associated with higher antibody responses, but this is only the start of the story,” said Julian Knight, professor of genomic medicine at the university’s Wellcome Centre for Human Genetics and chief investigator of the study. He continued: “Further work is needed to better understand the clinical significance of this specific association, and more broadly what identifying this gene variant can tell us about how effective immune responses are generated and ways to continue to improve vaccines for everyone.” The researchers initially analysed DNA samples from 1,190 participants who enrolled at the University of Oxford’s COVID-19 vaccine clinical trials, as well as from 1,677 adults who had enrolled on the com-COV research programme. They also looked at DNA samples from children who had participated in clinical trials for the Oxford-AstraZeneca vaccine. Dr Alexander Mentzer, National Institute for Health and Care Research academic clinical lecturer at the Wellcome Centre for Human Genetics and a lead researcher on the study, added: “We have seen a wide variation in how quickly people test positive for COVID-19 after vaccination. Our findings suggest that our genetic code may influence how likely this is to happen over time. “We hope that our findings will help us improve vaccines for the future so they not only stop us developing severe disease, but also keep us symptom-free for as long as possible.”

VaccineCollaborateAntibody

26 May 2022

·www.worldpharmanews.com

Vaxzevria approved in the EU as third dose booster against COVID-19

AstraZeneca's COVID-19 vaccine, Vaxzevria (ChAdOx1-S [Recombinant]), has been granted approval in the European Union (EU) by the European Medicine Agency (EMA) as a third dose booster in adults. Healthcare professionals can now use Vaxzevria as a third dose booster in patients previously given a primary vaccine schedule of either Vaxzevria or an EU-approved mRNA COVID-19 vaccine. The authorisation is based on a review by the Committee for Medicinal Products for Human Use (CHMP) of the substantial body of evidence demonstrating an increased immune response after a third dose booster with Vaxzevria following a primary vaccine schedule of either Vaxzevria or an mRNA COVID-19 vaccine.(1-5) Although more than 65% of the global population has received at least one dose of a COVID-19 vaccine(6), there remains a significant challenge to ensure people receive both their primary vaccine schedule and third dose booster, and healthcare professionals now have greater flexibility in their choice of vaccine. Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca said: "Today's marketing authorisation for AstraZeneca's COVID-19 vaccine as a third dose booster is an important step towards our goal of providing continued protection against COVID-19 for all populations. Ensuring a longer duration of immune protection is essential to the long-term management of COVID-19 globally, and boosters can address the waning of protection over time that has been seen with all primary vaccine schedules to date." There is a substantial body of evidence supporting Vaxzevria as a third dose booster following all primary vaccination schedules tested to date including Vaxzevria, mRNA vaccines, and CoronaVac.(1,7-12) Vaxzevria is already authorised as a homologous booster (patients previously given a primary vaccine schedule of Vaxevria) in the UK, and several countries in Asia and Latin America. It has also been authorised as a heterologous booster (patients previously given a primary vaccine schedule of either a viral vector vaccine other than Vaxzevria or an inactivated vaccine or an mRNA COVID-19 vaccine) in a number of non-EU countries. Vaxzevria is estimated to have helped prevent 50 million COVID-19 cases, five million hospitalisations, and saved more than one million lives worldwide, based on model outcomes assessing COVID-19 worldwide.(13) About Vaxzevria (ChAdOx1-S [Recombinant], formerly AZD1222) AstraZeneca COVID-19 vaccine was invented by the University of Oxford. It uses a replication-deficient chimpanzee viral vector based on a weakened version of a common cold virus (adenovirus) that causes infections in chimpanzees and contains the genetic material of the SARS-CoV-2 virus spike protein. After vaccination, the surface spike protein is produced, priming the immune system to attack the SARS-CoV-2 virus if it later infects the body. Vaxzevria is a viral vector vaccine, which means a version of a virus that cannot cause disease is used as part of the vaccine, leaving the body knowing how to fight it if it is exposed to the real virus later. This vaccine technology has been used by scientists over the past 40 years to fight other infectious diseases such as the flu, Ebola, and HIV.(14) The vaccine has been granted a conditional marketing authorisation or emergency use in more than 125 countries. It also has Emergency Use Listing from the World Health Organization, which accelerates the pathway to access in up to 144 countries through the COVAX Facility. Under a sub-license agreement with AstraZeneca, the vaccine is manufactured and supplied by the Serum Institute of India under the name COVISHIELD. About AstraZeneca AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. 1. Maheshi N Ramasamy et al. Immunogenicity and safety of AZD1222 (ChAdOx1 nCoV-19) and AZD2816 as third-dose boosters in adults previously vaccinated with AZD1222 or an mRNA vaccine. Presented at the European Society of Clinical Microbiology and Infectious Diseases Congress (ECCMID), Lisbon, 2022. 2. Flaxman A, et al. Reactogenicity and immunogenicity after a late second dose or a third dose of ChAdOx1 nCoV-19 (AZD1222) in the UK: a substudy of two randomized controlled trials (COV001 and COV002). The Lancet. Available at: https://www.thelancet.com/article/S0140-6736(21)01699-8/fulltext. Accessed May 2022. 3. Munro A PS, et al. Safety and immunogenicity of seven COVID-19 vaccines as a third dose (booster) following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK (COV-BOOST): a blinded, multicentre, randomised, controlled, phase 2 trial. The Lancet. Available at: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02717-3/fulltext. Accessed May 2022. 4. Participants were adults 18 years-old and older who would benefit from prevention with Evusheld, defined as having increased risk for inadequate response to active immunisation (predicted poor responders to vaccines or intolerant to vaccination) or having increased risk Liu X et al. Safety and immunogenicity of heterologous versus homologous prime-boost schedules with an adenoviral vectored and mRNA COVID-19 vaccine (Com-COV): a single-blind, randomised, non-inferiority trial. Available at: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01694-9/fulltext. Accessed May 2022. 5. Dejnirattisai W et al. SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses. Available at: https://www.sciencedirect.com/science/article/pii/S0092867421015786. Accessed May 2022. 6. Ritchie et al. Coronavirus (COVID-19) Vaccinations - Our World in Data. Accessed at: https://ourworldindata.org/covid-vaccinations. Accessed May 2022 7. Flaxman A, et al. Reactogenicity and immunogenicity after a late second dose or a third dose of ChAdOx1 nCoV-19 (AZD1222) in the UK: a substudy of two randomized controlled trials (COV001 and COV002). The Lancet. Available at: https://www.thelancet.com/article/S0140-6736(21)01699-8/fulltext. Accessed May 2022. 8. Munro A PS, et al. Safety and immunogenicity of seven COVID-19 vaccines as a third dose (booster) following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK (COV-BOOST): a blinded, multicentre, randomised, controlled, phase 2 trial. The Lancet. Available at: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02717-3/fulltext. Accessed May 2022. 9. Jara A et al. Effectiveness of Homologous and Heterologous Booster Shots for an Inactivated SARS-CoV-2 Vaccine: A Large-Scale Observational Study. Available at SSRN: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4005130. Accessed May 2022. 10. Vargas L et al. Serological study of CoronaVac vaccine and booster doses in Chile: immunogenicity and persistence of anti-SARS-CoV-2 S antibodies. Pre-print available at: https://www.medrxiv.org/content/10.1101/2022.01.14.22269289v1. Accessed May 2022. 11. Costa Clemens SA, et al. Heterologous versus homologous COVID-19 booster vaccination in previous recipients of two doses of CoronaVac COVID-19 vaccine in Brazil (RHH-001): a phase 4, non-inferiority, single blind randomised study. Available at: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)00094-0/fulltext. Accessed May 2022. 12. Data estimates based on model outcomes with transmission defined as 200 infections per 100,000 people per day. AZD1222 lives and hospitalisations prevented data on file. Data on File Number: REF-131228, 10 November 2021. AstraZeneca UK Ltd. 13. Zhang et al. Adenoviral vector-based strategies against infectious disease and cancer. Available at: https://www.tandfonline.com/doi/full/10.1080/21645515.2016.1165908. Accessed May 2022

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100 Deals associated with AZD-2816

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Indication	Highest Phase	Country/Location	Organization	Date
COVID-19	Phase 3	BR	AstraZeneca PLC	27 Jun 2021
COVID-19	Phase 3	PL	AstraZeneca PLC	27 Jun 2021
COVID-19	Phase 3	ZA	AstraZeneca PLC	27 Jun 2021
COVID-19	Phase 3	GB	AstraZeneca PLC	27 Jun 2021

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


Pubmed \| Lancet Microbe	Not Applicable	COVID-19	-	AZD1222	ngnweittqt(clqeubneox) = ynyuxlvwij bakcwuxnut (avfjzvegcl ) View more	-	01 Nov 2023
				AZD2816	ngnweittqt(clqeubneox) = xwnspcobqc bakcwuxnut (avfjzvegcl ) View more

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