A Phase 2b/3, Randomized, Observer-Blinded, Placebo-Controlled, Multicenter Clinical Study Evaluating the Efficacy and Safety of Investigational SARS-CoV-2 mRNA Vaccine CVnCoV in Adults 18 Years of Age and Older

NCT ID: NCT04652102

Last Updated: 2024-04-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 39680 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-11
• Study Completion Date: 2022-06-10

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.

Detailed Description

This clinical trial information was submitted voluntarily under the applicable law and, therefore, certain submission deadlines may not apply. (That is, clinical trial information for this applicable clinical trial was submitted under section 402(j)(4)(A) of the Public Health Service Act and 42 CFR 11.60 and is not subject to the deadlines established by sections 402(j)(2) and (3) of the Public Health Service Act or 42 CFR 11.24 and 11.44.).

Conditions

Covid19; SARS-CoV-2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Randomized Observer-blinded Phase 2b: CVnCoV vaccine

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.

Group Type: EXPERIMENTAL

CVnCoV

Intervention Type: BIOLOGICAL

Intramuscular (IM) injection.

Randomized Observer-blinded Phase 2b: Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

Intramuscular (IM) injection.

Randomized Observer-blinded Phase 3: CVnCoV vaccine

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.

Group Type: EXPERIMENTAL

CVnCoV

Intervention Type: BIOLOGICAL

Intramuscular (IM) injection.

Randomized Observer-blinded Phase 3: Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

Intramuscular (IM) injection.

Open-label Phase

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.

Group Type: EXPERIMENTAL

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

Intervention Type: BIOLOGICAL

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

Interventions

CVnCoV

Intramuscular (IM) injection.

Intervention Type: BIOLOGICAL

Placebo

Intramuscular (IM) injection.

Intervention Type: BIOLOGICAL

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

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

Intervention Type: BIOLOGICAL

Other Intervention Names

CV07050101

Eligibility Criteria

Inclusion Criteria

• 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}.

Exclusion Criteria

• 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:

• Participants must have received at least 1 dose of CVnCoV during the randomized observer blinded phase.
• Participants must provide additional written informed consent to be eligible for the open label phase.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

CureVac

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Instituto de Investigaciones Clinicas Quilmes

Buenos Aires, , Argentina

Hospital Interzonal General Agudos Prof. Dr. Ramon Carrillo

Buenos Aires, , Argentina

Hospital Interzonal General de Agudos Vicente Lopez y Planes

Buenos Aires, , Argentina

Hospital Zonal General de Agudos Descentralizado Evita Pueblo de Berazategui

Buenos Aires, , Argentina

Fundación Cenit Para La Investigación En Neurociencias

Buenos Aires, , Argentina

Instituto de Investigaciones Clínicas Mar del Plata

Mar del Plata, , Argentina

Sanatorio Parque

Rosario, , Argentina

Corporación Médica Sanatorio

San Martín, , Argentina

Instituto De Investigaciones Clinica Zarate

Zárate, , Argentina

Cohezio - Bruxelles

Brussels, , Belgium

Mensura

Brussels, , Belgium

Universitair Ziekenhuis Gent

Ghent, , Belgium

Clínica de la Costa

Barranquilla, , Colombia

CAIMED - Bogota Clinical Research Center

Bogotá, , Colombia

Centro de Estudios en Infectología Pediátrica (CEIP)

Cali, , Colombia

Fundacion Dominicana de Perinatologia Pro Bebe

Santo Domingo, , Dominican Republic

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

Santo Domingo, , Dominican Republic

Clínica Cruz Jiminian

Santo Domingo, , Dominican Republic

Hospital General Regional Marcelino Vélez Santana

Santo Domingo, , Dominican Republic

Uniklinik Köln

Cologne, , Germany

Ludwig-Maximilians-Universität München

München, , Germany

Universitätsklinikum Tübingen - Institut für Tropenmedizin, Reisemedizin und Humanparasitologie

Tübingen, , Germany

Panamerican Clinical research Mexico (Guadalajara)

Guadalajara, , Mexico

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

Juriquilla, , Mexico

Instituto Nacional De Ciencias Medicas Y Nutricion Salvador Zubiran

Mexico City, , Mexico

CAIMED - México

Mexico City, , Mexico

Unidad de Medicina Especializada SMA

San Juan del Río, , Mexico

Centro Medico Zambrano Hellion TecSalud

San Pedro Garza García, , Mexico

Noordwest Ziekenhuisgroep

Alkmaar, , Netherlands

Amsterdam Universitair Medische Centra - Academisch Medisch Centrum

Amsterdam, , Netherlands

The Julius Center - Utrecht Science Park - Stratenum

Utrecht, , Netherlands

Centro De Vacunacion Internacional - CEVAXIN Chorreras

Panama City, , Panama

Instituto de Investigaciones Científicas y Servicios de Alta Tecnología

Panama City, , Panama

Centro De Vacunacion Internacional - CEVAXIN 24 Diciembre

Panama City, , Panama

Centro de Vacunacion Internacional - CEVAXIN Avenida Mexico

Panama City, , Panama

Centro de Investigaciones Tecnológicas, Biomédicas y Medioambientales

Callao, , Peru

Hospital de Chancay y Servicios básicos de Salud

Chancay, , Peru

Clinica Medica San Martin

Ica, , Peru

Instituto de Investigación Nutricional - Las Gardenias

Lima, , Peru

Instituto de Investigación Nutricional - San Carlos

Lima, , Peru

Instituto de Investigación Nutricional

Lima, , Peru

Asociación Civil Impacta Salud y Educación

Lima, , Peru

Centro de Investigación para ensayos Clínicos UPCH

Lima, , Peru

OSI Eskerraldea-Enkarterri-Cruces/Hospital Universitario Cruces

Barakaldo, , Spain

Hospital Universitario Donostia

Donostia / San Sebastian, , Spain

Hospital Clínico San Carlos

Madrid, , Spain

Countries

Argentina; Belgium; Colombia; Dominican Republic; Germany; Mexico; Netherlands; Panama; Peru; Spain

References

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.

Reference Type: DERIVED

PMID: 34826381 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2020-003998-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CV-NCOV-004

Identifier Type: -

Identifier Source: org_study_id