NCT04652102

Brief Summary

The primary objective of the randomized observer-blinded phase 2b/3 part of this trial is to demonstrate the efficacy of a 2-dose schedule of CVnCoV in the prevention of first episodes of virologically-confirmed cases of COVID-19 of any severity in SARS-CoV-2 naïve participants.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
39,680

participants targeted

Target at P75+ for phase_2 covid19

Timeline
Completed

Started Dec 2020

Longer than P75 for phase_2 covid19

Geographic Reach
10 countries

46 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 1, 2020

Completed
2 days until next milestone

First Posted

Study publicly available on registry

December 3, 2020

Completed
8 days until next milestone

Study Start

First participant enrolled

December 11, 2020

Completed
1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 10, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 10, 2022

Completed
1.9 years until next milestone

Results Posted

Study results publicly available

April 29, 2024

Completed
Last Updated

April 29, 2024

Status Verified

November 1, 2023

Enrollment Period

1.5 years

First QC Date

December 1, 2020

Results QC Date

December 9, 2022

Last Update Submit

November 20, 2023

Conditions

Covid19SARS-CoV-2

Keywords

Vaccine

Outcome Measures

Primary Outcomes (12)

  • Number of Participants Who Experienced a First Episode of Virologically-confirmed {Reverse Transcription Polymerase Chain Reaction (RT-PCR) Positive} Case of COVID-19 of Any Severity

    A case of COVID-19 meeting the definition for primary efficacy analysis was defined as follows: * Virologically-confirmed case of COVID-19 (of any severity) defined as a positive SARS-CoV-2 specific RT-PCR test in a person with clinically symptomatic COVID-19. * Symptom onset ≥ 15 days after second trial vaccination. * First episode of virologically-confirmed COVID-19, i.e. the participant must not have had a history of virologically-confirmed COVID-19 illness at enrollment or have had developed a case of virologically-confirmed COVID-19 before 15 days after the second trial vaccination. * Participant was SARS-CoV-2 naïve at baseline and Day 43 (defined as seronegative to N protein in the blood samples collected at baseline and Day 43). * Primary efficacy cases were confirmed by an Adjudication Committee. Participants were censored at the first day after unblinding or at the day after receiving the authorized/licensed vaccine, whichever was earlier.

    Day 44 to Day 393

  • Number of Participants Who Experienced One or More Medically-attended Adverse Events (AE)

    Medically-attended AEs were defined as AEs with medically-attended visits that were not routine visits for physical examination or vaccination, such as visits for hospitalization, an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason. Clinic visits for COVID-19 testing resulting in negative test results were not considered as medically attended visits, if there is no confirmed diagnosis and no prescribed concomitant medication. The Investigator assessed the relationship between trial vaccine and occurrence of each AE. Participants were censored at the first day after unblinding or at the day after receiving the authorized/licensed vaccine, whichever was earlier.

    Day 1 to Day 211

  • Number of Participants Who Experienced One or More Serious AE (SAE)

    An SAE was defined as any untoward medical occurrence that, at any dose: * Resulted in death. * Was life-threatening. * Required inpatient hospitalization or prolongation of existing hospitalization. * Resulted in persistent disability/incapacity. * Was a congenital anomaly/birth defect in the offspring of the participant. * Was an important medical event. The Investigator assessed the relationship between trial vaccine and occurrence of each SAE. Participants were censored at the first day after unblinding or at the day after receiving the authorized/licensed vaccine, whichever was earlier.

    Day 1 to Day 393

  • Intensity of SAEs as Per Investigator Assessment

    An SAE was defined as any untoward medical occurrence that, at any dose: * Resulted in death. * Was life-threatening. * Required inpatient hospitalization or prolongation of existing hospitalization. * Resulted in persistent disability/incapacity. * Was a congenital anomaly/birth defect in the offspring of the participant. * Was an important medical event. The Investigator made an assessment of intensity of each SAE reported during the trial. Each SAE was graded from Mild (Grade 1) to Severe (Grade 3), where higher grades indicated a worse outcome. Participants were censored at the first day after unblinding or at the day after receiving the authorized/licensed vaccine, whichever was earlier.

    Day 1 to Day 393

  • Number of Participants Who Experienced One or More Adverse Event of Special Interest (AESI)

    AESIs included: * AEs with a suspected immune-medicated etiology. * Other AEs relevant to SARS-CoV-2 vaccine development or the target disease. The Investigator assessed the relationship between trial vaccine and occurrence of each AESI. Participants were censored at the first day after unblinding or at the day after receiving the authorized/licensed vaccine, whichever was earlier.

    Day 1 to Day 393

  • Number of Participants Who Experienced a Fatal SAE

    A fatal SAE was defined as an SAE that resulted in death. Participants were censored at the first day after unblinding or at the day after receiving the authorized/licensed vaccine, whichever was earlier.

    Day 1 to Day 393

  • Phase 2b Participants Only: Number of Participants Who Experienced One or More Solicited AE

    Solicited local AEs (injection site pain, redness, swelling, and itching) and solicited systemic AEs (fever, headache, fatigue, chills, myalgia, arthralgia, nausea/vomiting, and diarrhea) were recorded on the day of vaccination and the following 7 days using an eDiary. Participants were censored at the first day after unblinding or at the day after receiving the authorized/licensed vaccine, whichever was earlier.

    Up to 7 days after vaccination (Days 1 to 7 and Days 29 to 36)

  • Phase 2b Participants Only: Intensity of Solicited AEs as Per Investigator Assessment

    Solicited local AEs (injection site pain, redness, swelling, and itching) and solicited systemic AEs (fever, headache, fatigue, chills, myalgia, arthralgia, nausea/vomiting, and diarrhea) were recorded on the day of vaccination and the following 7 days using an eDiary. The Investigator made an assessment of intensity of each solicited AE reported during the trial. Each solicited AE was graded from Mild (Grade 1) to Severe (Grade 3), where higher grades indicated a worse outcome. Participants were censored at the first day after unblinding or at the day after receiving the authorized/licensed vaccine, whichever was earlier.

    Up to 7 days after vaccination (Days 1 to 7 and Days 29 to 36)

  • Phase 2b Participants Only: Duration of Solicited AEs

    Solicited local AEs (injection site pain, redness, swelling, and itching) and solicited systemic AEs (fever, headache, fatigue, chills, myalgia, arthralgia, nausea/vomiting, and diarrhea) were recorded on the day of vaccination and the following 7 days using an eDiary. Duration is calculated as consecutive days with a respective solicited AE regardless of the grade of the AE. AEs ongoing after Day 8 are included. In each case only the longest consecutive duration is displayed. Participants were censored at the first day after unblinding or at the day after receiving the authorized/licensed vaccine, whichever was earlier.

    Up to 7 days after vaccination (Days 1 to 7 and Days 29 to 36)

  • Phase 2b Participants Only: Number of Participants Who Experienced One or More Unsolicited AE

    eDiaries were used for collection of unsolicited AEs on each vaccination day and the following 28 days. In addition, participants received a prompt (by e.g., a phone call or text message) to verify whether the participants had any health concerns since the last visit. The Investigator assessed the relationship between trial vaccine and each occurrence of each AE. Participants were censored at the first day after unblinding or at the day after receiving the authorized/licensed vaccine, whichever was earlier.

    Up to 28 days after vaccination (Days 1 to 29 and Days 29 to 57)

  • Phase 2b Participants Only: Intensity of Unsolicited AEs as Per Investigator Assessment

    eDiaries were used for collection of unsolicited AEs on each vaccination day and the following 28 days. In addition, participants received a prompt (by e.g., a phone call or text message) to verify whether the participants had any health concerns since the last visit. The Investigator made an assessment of intensity of each unsolicited AE reported during the trial. Each unsolicited AE was graded from Mild (Grade 1) to Severe (Grade 3), where higher grades indicated a worse outcome. Participants were censored at the first day after unblinding or at the day after receiving the authorized/licensed vaccine, whichever was earlier.

    Up to 28 days after vaccination (Days 1 to 29 and Days 29 to 57)

  • Number of Participants Who Experienced One or More AEs Leading to Vaccine Withdrawal or Trial Discontinuation

    Participants were censored at the first day after unblinding or at the day after receiving the authorized/licensed vaccine, whichever was earlier.

    Day 1 to Day 393

Secondary Outcomes (10)

  • Number of Participants Who Experienced a First Episode of Virologically-confirmed (RT-PCR Positive) Moderate to Severe Case of COVID-19

    Day 44 to Day 393

  • Number of Participants Who Experienced a First Episode of Virologically-confirmed (RT-PCR Positive) Severe Case of COVID-19

    Day 44 to Day 393

  • Number of Participants Who Experienced a First Episode of Virologically-confirmed (RT-PCR Positive) Case of COVID-19 of Any Severity Due to Infection With "Wild Type" and "Alpha" SARS-CoV-2 Strains in SARS-CoV-2 Naïve Participants

    Day 44 to Day 393

  • Number of Participants Aged ≥ 61 Who Experienced a First Episode of Virologically-confirmed (RT-PCR Positive) Case of COVID-19 of Any Severity

    Day 44 to Day 393

  • Burden of Disease (BoD) Score #1 Based on First Episodes of Virologically-confirmed (RT-PCR Positive) Cases of COVID-19

    Day 44 to Day 393

  • +5 more secondary outcomes

Study Arms (5)

Randomized Observer-blinded Phase 2b: CVnCoV vaccine

EXPERIMENTAL

Participants will be vaccinated with CVnCoV 12 µg vaccine on Day 1 and Day 29 in the deltoid area, preferably in the non-dominant arm.

Biological: CVnCoV

Randomized Observer-blinded Phase 2b: Placebo

PLACEBO COMPARATOR

Participants will be administered the matching placebo on Day 1 and Day 29 in the deltoid area, preferably in the non-dominant arm.

Biological: Placebo

Randomized Observer-blinded Phase 3: CVnCoV vaccine

EXPERIMENTAL

Participants will be vaccinated with CVnCoV 12 µg vaccine on Day 1 and Day 29 in the deltoid area, preferably in the non-dominant arm.

Biological: CVnCoV

Randomized Observer-blinded Phase 3: Placebo

PLACEBO COMPARATOR

Participants will be administered the matching placebo on Day 1 and Day 29 in the deltoid area, preferably in the non-dominant arm.

Biological: Placebo

Open-label Phase

EXPERIMENTAL

After unblinding, the trial will shift from a randomized observer-blinded to an open-label design, and the following cohorts will be defined: Cohort A: participants who received at least 1 dose of CVnCoV in the randomized observer-blinded phases and choose to receive an authorized/licensed vaccine for preventing COVID-19 (AV) as standard of care through their national vaccination program. Cohort B: participants who received at least 1 dose of CVnCoV in the randomized observer-blinded phases and choose to remain in the trial without receiving any AV. Participants on the placebo arm will be withdrawn.

Biological: Authorized/licensed vaccines for preventing COVID-19 (AV) as standard of care through their national vaccination program

Interventions

CVnCoVBIOLOGICAL

Intramuscular (IM) injection.

Also known as: CV07050101
Randomized Observer-blinded Phase 2b: CVnCoV vaccineRandomized Observer-blinded Phase 3: CVnCoV vaccine
PlaceboBIOLOGICAL

Intramuscular (IM) injection.

Randomized Observer-blinded Phase 2b: PlaceboRandomized Observer-blinded Phase 3: Placebo
Authorized/licensed vaccines for preventing COVID-19 (AV) as standard of care through their national vaccination programBIOLOGICAL

Intramuscular (IM) injection will be received as standard of care (SoC) outside the study.

Open-label Phase

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Male or female participants 18 years of age or older.
  • Be willing and able to provide written informed consent prior to initiation of any trial procedures.
  • Expected compliance with protocol procedures and availability for clinical follow-up through the last planned visit.
  • Females of non-childbearing potential defined as follows: surgically sterile (history of bilateral tubal ligation/occlusion, bilateral oophorectomy or hysterectomy) or postmenopausal {defined as amenorrhea for ≥12 consecutive months prior to screening (Day 1) without an alternative medical cause}. A follicle-stimulating hormone (FSH) level may be measured at the discretion of the Investigator to confirm postmenopausal status.
  • Females of childbearing potential: negative pregnancy test (human chorionic gonadotropin \[hCG\]) within 24 hours prior to each trial vaccination on Day 1 and Day 29.
  • Females of childbearing potential must use highly effective methods of birth control from 2 weeks before the first administration of the trial vaccine until 3 months following the last administration. The following methods of birth control are considered highly effective when used consistently and correctly:
  • Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal);
  • Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable);
  • Intrauterine devices;
  • Intrauterine hormone-releasing systems;
  • Bilateral tubal ligation;
  • Vasectomized or infertile partner;
  • Sexual abstinence {periodic abstinence (e.g., calendar, ovulation, symptothermal and post-ovulation methods) and withdrawal are not acceptable}.

You may not qualify if:

  • History of virologically-confirmed COVID-19 illness.
  • For females: pregnancy or lactation.
  • Use of any investigational or non-registered product (vaccine or drug) within 28 days preceding the administration of trial vaccine or planned use during the trial.
  • Receipt of any licensed vaccines within 28 days (for live vaccines) or 14 days (for inactivated or any other vaccines) prior to administration of the first trial vaccine.
  • Prior administration of any investigational SARS-CoV-2 vaccine or another coronavirus (SARS-CoV, Middle East Respiratory Syndrome-CoV) vaccine or planned used during the trial.
  • Any treatment with immunosuppressants or other immune-modifying drugs (including but not limited to anabolic steroids, corticosteroids, biologicals and methotrexate) for \> 14 days total within 6 months preceding the administration of trial vaccine or planned use during the trial. For corticosteroid use, this means prednisone or equivalent, 0.5 mg/kg/day for 14 days or more. The use of inhaled, topical, or localized injections of corticosteroids (e.g., for joint pain/inflammation) is permitted.
  • Any medically diagnosed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination including known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV); current diagnosis of or treatment for cancer including leukemia, lymphoma, Hodgkin disease, multiple myeloma or generalized malignancy; chronic renal failure or nephrotic syndrome; and receipt of an organ or bone marrow transplant.
  • History of angioedema (hereditary or idiopathic) or history of any anaphylactic reaction.
  • History of potential immune-mediated disease (pIMD).
  • History of allergy to any component of CVnCoV.
  • Administration of immunoglobulins or any blood products within 3 months prior to the administration of trial vaccine or planned receipt during the trial.
  • Participants with a significant acute or chronic medical or psychiatric illness that, in the opinion of the Investigator, precludes trial participation (e.g., may increase the risk of trial participation, render the participant unable to meet the requirements of the trial, or may interfere with the participant's trial evaluations). These include severe and/or uncontrolled cardiovascular disease, gastrointestinal disease, liver disease, renal disease, respiratory disease, endocrine disorder, and neurological and psychiatric illnesses. However, those with controlled and stable cases can be included in the trial.
  • Participants with impaired coagulation or any bleeding disorder in whom an IM injection or a blood draw is contraindicated.
  • Foreseeable non-compliance with the trial procedure as judged by the Investigator.
  • Roll-over Criteria for the Open-label Phase:
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (46)

Instituto de Investigaciones Clinicas Quilmes

Buenos Aires, 1878, Argentina

Location

Hospital Interzonal General Agudos Prof. Dr. Ramon Carrillo

Buenos Aires, B1702FWM, Argentina

Location

Hospital Interzonal General de Agudos Vicente Lopez y Planes

Buenos Aires, B1748, Argentina

Location

Hospital Zonal General de Agudos Descentralizado Evita Pueblo de Berazategui

Buenos Aires, B1884LAD, Argentina

Location

Fundación Cenit Para La Investigación En Neurociencias

Buenos Aires, C1125 ABD, Argentina

Location

Instituto de Investigaciones Clínicas Mar del Plata

Mar del Plata, B7600FZN, Argentina

Location

Sanatorio Parque

Rosario, S2000, Argentina

Location

Corporación Médica Sanatorio

San Martín, B1650CSQ, Argentina

Location

Instituto De Investigaciones Clinica Zarate

Zárate, B2800DGH, Argentina

Location

Cohezio - Bruxelles

Brussels, 1000, Belgium

Location

Mensura

Brussels, 1030, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

Clínica de la Costa

Barranquilla, 80020, Colombia

Location

CAIMED - Bogota Clinical Research Center

Bogotá, 111621, Colombia

Location

Centro de Estudios en Infectología Pediátrica (CEIP)

Cali, 760042, Colombia

Location

Fundacion Dominicana de Perinatologia Pro Bebe

Santo Domingo, 10204, Dominican Republic

Location

Instituto Dermatológico Dominicano y Cirugía de Piel Dr. Huberto Bogaert Díaz

Santo Domingo, 10305, Dominican Republic

Location

Clínica Cruz Jiminian

Santo Domingo, 10501, Dominican Republic

Location

Hospital General Regional Marcelino Vélez Santana

Santo Domingo, 11001, Dominican Republic

Location

Uniklinik Köln

Cologne, 50937, Germany

Location

Ludwig-Maximilians-Universität München

München, 80802, Germany

Location

Universitätsklinikum Tübingen - Institut für Tropenmedizin, Reisemedizin und Humanparasitologie

Tübingen, 72074, Germany

Location

Panamerican Clinical research Mexico (Guadalajara)

Guadalajara, 44690, Mexico

Location

Panamerican Clinical Research Mexico S.A. DE C.V.

Juriquilla, 76226, Mexico

Location

Instituto Nacional De Ciencias Medicas Y Nutricion Salvador Zubiran

Mexico City, 14080, Mexico

Location

CAIMED - México

Mexico City, 6760, Mexico

Location

Unidad de Medicina Especializada SMA

San Juan del Río, 76800, Mexico

Location

Centro Medico Zambrano Hellion TecSalud

San Pedro Garza García, 66278, Mexico

Location

Noordwest Ziekenhuisgroep

Alkmaar, 1815JD, Netherlands

Location

Amsterdam Universitair Medische Centra - Academisch Medisch Centrum

Amsterdam, 1105 AZ, Netherlands

Location

The Julius Center - Utrecht Science Park - Stratenum

Utrecht, 3584 CX, Netherlands

Location

Centro De Vacunacion Internacional - CEVAXIN Chorreras

Panama City, 07064, Panama

Location

Instituto de Investigaciones Científicas y Servicios de Alta Tecnología

Panama City, 07097, Panama

Location

Centro De Vacunacion Internacional - CEVAXIN 24 Diciembre

Panama City, 07113, Panama

Location

Centro de Vacunacion Internacional - CEVAXIN Avenida Mexico

Panama City, 10662, Panama

Location

Centro de Investigaciones Tecnológicas, Biomédicas y Medioambientales

Callao, 07006, Peru

Location

Hospital de Chancay y Servicios básicos de Salud

Chancay, 15131, Peru

Location

Clinica Medica San Martin

Ica, 11000, Peru

Location

Instituto de Investigación Nutricional - Las Gardenias

Lima, 15024, Peru

Location

Instituto de Investigación Nutricional - San Carlos

Lima, 15024, Peru

Location

Instituto de Investigación Nutricional

Lima, 15024, Peru

Location

Asociación Civil Impacta Salud y Educación

Lima, 15063, Peru

Location

Centro de Investigación para ensayos Clínicos UPCH

Lima, 15102, Peru

Location

OSI Eskerraldea-Enkarterri-Cruces/Hospital Universitario Cruces

Barakaldo, 48903, Spain

Location

Hospital Universitario Donostia

Donostia / San Sebastian, 20014, Spain

Location

Hospital Clínico San Carlos

Madrid, 28040, Spain

Location

Related Publications (1)

  • Kremsner PG, Ahuad Guerrero RA, Arana-Arri E, Aroca Martinez GJ, Bonten M, Chandler R, Corral G, De Block EJL, Ecker L, Gabor JJ, Garcia Lopez CA, Gonzales L, Granados Gonzalez MA, Gorini N, Grobusch MP, Hrabar AD, Junker H, Kimura A, Lanata CF, Lehmann C, Leroux-Roels I, Mann P, Martinez-Resendez MF, Ochoa TJ, Poy CA, Reyes Fentanes MJ, Rivera Mejia LM, Ruiz Herrera VV, Saez-Llorens X, Schonborn-Kellenberger O, Schunk M, Sierra Garcia A, Vergara I, Verstraeten T, Vico M, Oostvogels L; HERALD Study Group. Efficacy and safety of the CVnCoV SARS-CoV-2 mRNA vaccine candidate in ten countries in Europe and Latin America (HERALD): a randomised, observer-blinded, placebo-controlled, phase 2b/3 trial. Lancet Infect Dis. 2022 Mar;22(3):329-340. doi: 10.1016/S1473-3099(21)00677-0. Epub 2021 Nov 23.

    PMID: 34826381DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

CVnCoV COVID-19 vaccine

Condition Hierarchy (Ancestors)

Pneumonia, ViralPneumoniaRespiratory Tract InfectionsInfectionsVirus DiseasesCoronavirus InfectionsCoronaviridae InfectionsNidovirales InfectionsRNA Virus InfectionsLung DiseasesRespiratory Tract Diseases

Results Point of Contact

Title
Clinical Trial Information
Organization
CureVac AG
clinicaltrials@curevac.com
0049 6976805870

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Masking Details
The randomized observer-blinded phases of this study are participant and investigator blinded. This is followed by an open-label phase.
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 1, 2020

First Posted

December 3, 2020

Study Start

December 11, 2020

Primary Completion

June 10, 2022

Study Completion

June 10, 2022

Last Updated

April 29, 2024

Results First Posted

April 29, 2024

Record last verified: 2023-11

Locations

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