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Efficacy and Safety of the CVnCoV SARS-CoV-2 mRNA Vaccine Candidate: Results from Herald, a Phase 2b/3, Randomised, Observer-Blinded, Placebo-Controlled Clinical Trial in Ten Countries in Europe and Latin America

29 Pages Posted: 27 Aug 2021

See all articles by Peter G. Kremsner

Peter G. Kremsner

Lambaréné Medical Research Center (CERMEL), Lambaréné

Rodolfo Andrés Ahuad Guerrero

Corporacion Medica de General San Martin

Eunate Arana

University of the Basque Country - Biocruces Bizkaia Health Research Institute

Gustavo Jose Aroca Martinez

Universidad Simón Bolívar (USB) - Clínica de la Costa

Marc J.M. Bonten

Utrecht University - Julius Center for Health Sciences and Primary Care

Reynaldo Chandler

Cevaxin

Gonzalo Corral

Instituto de Investigaciones Clinicas de Mar del Plata

Eddie Jan Louis De Block

Cohezio

Lucie Ecker

Instituto de Investigación Nutricional

Julian Justin Gabor

University of Tuebingen - Institute of Tropical Medicine

Carlos Alberto Garcia Lopez

Unidad de Medicina Especializada

Lucy Gonzales

Clinica Medica San Martin

María Angélica Granados González

Centro de Atención e Investigación Médica (CAIMED)

Nestor Gorini

Hospital Zonal General de Agudos Descentralizado Evita Pueblo de Berazategui

Martin P. Grobusch

Lambaréné Medical Research Center (CERMEL), Lambaréné; University of Amsterdam - Amsterdam Institute for Infection and Immunity; Masanga Hospital - Masanga Medical Research Unit

Adrian D. Hrabar

Clinical Research Institute Quilmes (Instituto de Investigaciones Clínicas Quilmes)

Helga Junker

CureVac AG

Alan Kimura

CureVac AG

Claudio F. Lanata

Instituto de Investigación Nutricional

Clara Lehmann

University of Cologne - Division of Infectious Diseases

Isabel Leroux-Roels

Ghent University - Center for Vaccinology (CEVAC)

Philipp Mann

CureVac AG

Michel Fernando Martinez-Reséndez

TecSalud - School of Medicine and Health Sciences

Theresa Ochoa

Universidad Peruana Cayetano Heredia - Instituto de Medicina Tropical Alexander von Humboldt

Carlos Alberto Poy

Sanatorio Parque S.A. Rosario

Maria Jose Reyes Fentanes

PanAmerican Clinical Research

Luis Maria Rivera Mejia

Hospital Universitario Maternidad Nuestra Señora de La Altagracia - Fundacion Dominicana de Perinatologia PRO-BEBE, Inc.

Vida Veronica Ruiz Herrera

PanAmerican Clinical Research

Xavier Sáez-Llorens

Hospital del Niño Dr. José Renán Esquivel

Oliver Schönborn-Kellenberger

Cogitars GmbH

Mirjam Schunk

Ludwig Maximilian University of Munich (LMU) - Division of Infectious Diseases and Tropical Medicine

Alexandra Sierra Garcia

Centro de estudios en Infectologia Pediatrica (CEIP)

Itziar Vergara

Biodonostia Health Research Institute - Primary Care Group

Thomas Verstraeten

P95 Pharmacovigilance and Epidemiology Services

Marisa Vico

Instituto de Investigaciones Clínicas Zárate

Lidia Oostvogels

CureVac AG

HERALD Study Group

Independent

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Abstract

Background: Additional safe and effective vaccines are needed to control the COVID-19 pandemic.

Methods: HERALD is an ongoing phase 2b/3 randomised, observer-blinded, placebo-controlled clinical trial in ten countries in Europe and Latin America. SARS-CoV-2 naïve adults were randomised 1:1 to receive two doses of CVnCoV mRNA vaccine candidate or placebo 28 days apart. Primary efficacy analysis included symptomatic COVID-19 more than 14 days after second dose. Solicited adverse events (AEs) were assessed in phase 2b participants and unsolicited AEs in all participants. The study is registered at ClinicalTrials.gov (NCT04652102).

Findings: Between 11 December 2020 and 12 April 2021, 39 680 participants were randomised and 39 529 received CVnCoV (19 783) or placebo (19 746). Overall VE was 48·2% (95% CI: 31·0–61·4; 83/12 851 vs. 145/12 221 in CVnCoV and placebo recipients, respectively). Overall VE against moderate-to-severe COVID-19 was 70·7% (95% CI: 42·5–86·1; 12/12 851 vs. 37/12 211, respectively). In participants aged 18–60 years VE was 52·5% (95% CI: 36·2–64·8; 71/11 532 vs. 136/11 031, respectively). Too few cases occurred in participants aged ≥61 years (CVnCoV: 12, placebo: 9) precluding VE evaluation. Wild type SARS-CoV-2 was detected in 7/204 (3%) sequenced cases, with 14 variants being responsible for the other cases. Solicited adverse events, mostly systemic, were more common in CVnCoV recipients; 542/2002 CVnCoV recipients and 61/1980 placebo recipients reported grade 3 events. Unsolicited serious AEs were reported for 82/19 746 CVnCoV recipients and 66/19 746 placebo recipients; 8 and 2 SAEs, respectively were considered related to vaccination. Fatal SAEs were reported for 8 and 6 CVnCoV and placebo recipients.

Interpretation: CVnCoV is efficacious in the prevention of COVID-19 of any severity and has an acceptable safety profile.

Trial Registration: Study number: ClinicalTrials.gov Identifier: NCT04652102.

Funding: This trial was funded by the German Federal Ministry of Education and Research (grant
01KI20703), and CureVac AG.

Declaration of Interest: MB declares institutional funding from CureVac during the conduct of this study, from Janssen Vaccines, molecular partners, and Merck outside of the submitted work, and consulting fees from Janssen Vaccines. EJLDB, and MFMR, TO and XSL declare institutional funding from CureVac during the conduct of this study. LE, and LG declare institutional funding from CureVac during the conduct of this study and outside of the submitted work. CFL declares institutional funding from CureVac during the conduct of this study, and outside of the submitted work, and is a member of WHO Covid-19 Vaccine Effectiveness Working Group and WHO Product Development for Vaccines Advisory Committee (PDVAC). CL declares institutional funding from CureVac during the conduct of this study, and is a member of the of German Society of Infection board. ILR declares institutional funding from CureVac during the conduct of this study and from J &J, and OSE Immunotherapeutics outside of the submitted work. PGK declares institutional funding from CureVac during the conduct of this study, and is a member of the scientific advisory board for the HERALD clinical trial. VVRH declares institutional funding from CureVac during the conduct of this study, and speakers fees from Gilead outside of the submitted work. HJ declares consultant fees from CureVac, is the Medical Responsible Person for the HERALD clinical trial, and is co-chair of DSMB for the HERALD clinical trial. AK and PM are employed by CureVac, and hold stock options. OSK declares consultant fees from CureVac during the conduct of this study, and is a member of the DSMB for a CVnCoV phase 1 trial. TV declares consultant fees from CureVac during the conduct of this study, and consultant fees from CureVac, AstraZeneca, Pfizer, Johnson&Johnson, and Moderna outside of the submitted work. LO is employed by CureVac, and holds stock options, and is the holder of a pending patent. The other authors declare no competing interests.

Ethical Approval: The trial protocol and amendments have been approved by the appropriate independent ethics committee or institutional review board at each study centre

Keywords: CVnCoV mRNA vaccine; SARS-CoV-2; COVID-19; adults; randomised clinical trial

Suggested Citation

Kremsner, Peter G. and Guerrero, Rodolfo Andrés Ahuad and Arana, Eunate and Aroca Martinez, Gustavo Jose and Bonten, Marc J.M. and Chandler, Reynaldo and Corral, Gonzalo and De Block, Eddie Jan Louis and Ecker, Lucie and Gabor, Julian Justin and Garcia Lopez, Carlos Alberto and Gonzales, Lucy and Granados González, María Angélica and Gorini, Nestor and Grobusch, Martin P. and Grobusch, Martin P. and Hrabar, Adrian D. and Junker, Helga and Kimura, Alan and Lanata, Claudio F. and Lehmann, Clara and Leroux-Roels, Isabel and Mann, Philipp and Martinez-Reséndez, Michel Fernando and Ochoa, Theresa and Poy, Carlos Alberto and Reyes Fentanes, Maria Jose and Mejia, Luis Maria Rivera and Ruiz Herrera, Vida Veronica and Sáez-Llorens, Xavier and Schönborn-Kellenberger, Oliver and Schunk, Mirjam and Garcia, Alexandra Sierra and Vergara, Itziar and Verstraeten, Thomas and Vico, Marisa and Oostvogels, Lidia and Group, HERALD Study, Efficacy and Safety of the CVnCoV SARS-CoV-2 mRNA Vaccine Candidate: Results from Herald, a Phase 2b/3, Randomised, Observer-Blinded, Placebo-Controlled Clinical Trial in Ten Countries in Europe and Latin America. Available at SSRN: https://ssrn.com/abstract=3911826 or http://dx.doi.org/10.2139/ssrn.3911826

Peter G. Kremsner (Contact Author)

Lambaréné Medical Research Center (CERMEL), Lambaréné ( email )

Rodolfo Andrés Ahuad Guerrero

Corporacion Medica de General San Martin ( email )

Buenos Aires
Argentina

Eunate Arana

University of the Basque Country - Biocruces Bizkaia Health Research Institute ( email )

Spain

Gustavo Jose Aroca Martinez

Universidad Simón Bolívar (USB) - Clínica de la Costa ( email )

Colombia

Marc J.M. Bonten

Utrecht University - Julius Center for Health Sciences and Primary Care ( email )

Utrecht
Netherlands

Reynaldo Chandler

Cevaxin ( email )

Panama City
Panama

Gonzalo Corral

Instituto de Investigaciones Clinicas de Mar del Plata ( email )

Argentina

Eddie Jan Louis De Block

Cohezio ( email )

1000 Brussels
Belgium

Lucie Ecker

Instituto de Investigación Nutricional ( email )

Lima
Peru

Julian Justin Gabor

University of Tuebingen - Institute of Tropical Medicine ( email )

Tübingen
Germany

Carlos Alberto Garcia Lopez

Unidad de Medicina Especializada ( email )

San Juan del Río
Queretaro
Mexico

Lucy Gonzales

Clinica Medica San Martin ( email )

Peru

María Angélica Granados González

Centro de Atención e Investigación Médica (CAIMED) ( email )

Bogotá
Colombia

Nestor Gorini

Hospital Zonal General de Agudos Descentralizado Evita Pueblo de Berazategui ( email )

Argentina

Martin P. Grobusch

Lambaréné Medical Research Center (CERMEL), Lambaréné ( email )

Gabon

University of Amsterdam - Amsterdam Institute for Infection and Immunity ( email )

Amsterdam
Netherlands

Masanga Hospital - Masanga Medical Research Unit ( email )

Masanga
Sierra Leone

Adrian D. Hrabar

Clinical Research Institute Quilmes (Instituto de Investigaciones Clínicas Quilmes) ( email )

Argentina

Helga Junker

CureVac AG ( email )

Tübingen
Germany

Alan Kimura

CureVac AG ( email )

Tübingen
Germany

Claudio F. Lanata

Instituto de Investigación Nutricional ( email )

Lima
Peru

Clara Lehmann

University of Cologne - Division of Infectious Diseases

Germany

Isabel Leroux-Roels

Ghent University - Center for Vaccinology (CEVAC) ( email )

Gent
Belgium

Philipp Mann

CureVac AG ( email )

Tübingen
Germany

Michel Fernando Martinez-Reséndez

TecSalud - School of Medicine and Health Sciences ( email )

Monterrey
Mexico

Theresa Ochoa

Universidad Peruana Cayetano Heredia - Instituto de Medicina Tropical Alexander von Humboldt ( email )

Lima
Peru

Carlos Alberto Poy

Sanatorio Parque S.A. Rosario ( email )

Argentina

Maria Jose Reyes Fentanes

PanAmerican Clinical Research ( email )

Mexico

Luis Maria Rivera Mejia

Hospital Universitario Maternidad Nuestra Señora de La Altagracia - Fundacion Dominicana de Perinatologia PRO-BEBE, Inc. ( email )

Dominican Republic

Vida Veronica Ruiz Herrera

PanAmerican Clinical Research ( email )

Mexico

Xavier Sáez-Llorens

Hospital del Niño Dr. José Renán Esquivel ( email )

Panama

Oliver Schönborn-Kellenberger

Cogitars GmbH ( email )

Germany

Mirjam Schunk

Ludwig Maximilian University of Munich (LMU) - Division of Infectious Diseases and Tropical Medicine ( email )

Munich
Germany

Alexandra Sierra Garcia

Centro de estudios en Infectologia Pediatrica (CEIP) ( email )

Colombia

Itziar Vergara

Biodonostia Health Research Institute - Primary Care Group ( email )

Spain

Thomas Verstraeten

P95 Pharmacovigilance and Epidemiology Services ( email )

Belgium

Marisa Vico

Instituto de Investigaciones Clínicas Zárate ( email )

Argentina

Lidia Oostvogels

CureVac AG ( email )

Tübingen
Germany

HERALD Study Group

Independent