Clinical trial NCT04652102: 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
Official title: COVID-19: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Covid19
SARS-CoV-2
Keywords: Vaccine
Lead sponsor: CureVac
Sponsor class: INDUSTRY
First posted: 2020-12-03
Enrollment: 39680
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.).

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.

Primary outcomes:
measure: 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
timeFrame: Day 44 to Day 393
measure: Number of Participants Who Experienced One or More Medically-attended Adverse Events (AE)
timeFrame: Day 1 to Day 211
measure: Number of Participants Who Experienced One or More Serious AE (SAE)
timeFrame: Day 1 to Day 393
measure: Intensity of SAEs as Per Investigator Assessment
timeFrame: Day 1 to Day 393
measure: Number of Participants Who Experienced One or More Adverse Event of Special Interest (AESI)
timeFrame: Day 1 to Day 393
measure: Number of Participants Who Experienced a Fatal SAE
timeFrame: Day 1 to Day 393
measure: Phase 2b Participants Only: Number of Participants Who Experienced One or More Solicited AE
timeFrame: Up to 7 days after vaccination (Days 1 to 7 and Days 29 to 36)
measure: Phase 2b Participants Only: Intensity of Solicited AEs as Per Investigator Assessment
timeFrame: Up to 7 days after vaccination (Days 1 to 7 and Days 29 to 36)
measure: Phase 2b Participants Only: Duration of Solicited AEs
timeFrame: Up to 7 days after vaccination (Days 1 to 7 and Days 29 to 36)
measure: Phase 2b Participants Only: Number of Participants Who Experienced One or More Unsolicited AE
timeFrame: Up to 28 days after vaccination (Days 1 to 29 and Days 29 to 57)
measure: Phase 2b Participants Only: Intensity of Unsolicited AEs as Per Investigator Assessment
timeFrame: Up to 28 days after vaccination (Days 1 to 29 and Days 29 to 57)
measure: Number of Participants Who Experienced One or More AEs Leading to Vaccine Withdrawal or Trial Discontinuation
timeFrame: Day 1 to Day 393
Secondary outcomes:
measure: Number of Participants Who Experienced a First Episode of Virologically-confirmed (RT-PCR Positive) Moderate to Severe Case of COVID-19
timeFrame: Day 44 to Day 393
measure: Number of Participants Who Experienced a First Episode of Virologically-confirmed (RT-PCR Positive) Severe Case of COVID-19
timeFrame: Day 44 to Day 393
measure: 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
timeFrame: Day 44 to Day 393
measure: Number of Participants Aged ≥ 61 Who Experienced a First Episode of Virologically-confirmed (RT-PCR Positive) Case of COVID-19 of Any Severity
timeFrame: Day 44 to Day 393
measure: Burden of Disease (BoD) Score #1 Based on First Episodes of Virologically-confirmed (RT-PCR Positive) Cases of COVID-19
timeFrame: Day 44 to Day 393
measure: BoD Score #2 Based on First Episodes of Virologically-confirmed (RT-PCR Positive) Cases of COVID-19
timeFrame: Day 44 to Day 393
measure: SARS-CoV-2 Receptor Binding Domain (RBD) of Spike (S) Protein Antibody Levels on Days 1, 29, 43, 120 and 211
timeFrame: Days 1 (baseline), 29, 43, 120 and 211
measure: Percentage of Participants Seroconverting to SARS-CoV-2 RBD of S Protein Antibodies on Days 29, 43, 120 and 211
timeFrame: Baseline and Days 29, 43, 120 and 211
measure: SARS-CoV-2 Viral Neutralizing Antibody Levels on Days 1, 29, 43, 120 and 211
timeFrame: Days 1 (baseline), 29, 43, 120 and 211
measure: Percentage of Participants Seroconverting to SARS-CoV-2 Viral Neutralizing Antibodies on Days 29, 43, 120 and 211
timeFrame: Baseline and Days 29, 43, 120 and 211
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: Instituto de Investigaciones Clinicas Quilmes
city: Buenos Aires
country: Argentina
facility: Hospital Interzonal General Agudos Prof. Dr. Ramon Carrillo
city: Buenos Aires
country: Argentina
facility: Hospital Interzonal General de Agudos Vicente Lopez y Planes
city: Buenos Aires
country: Argentina
facility: Hospital Zonal General de Agudos Descentralizado Evita Pueblo de Berazategui
city: Buenos Aires
country: Argentina
facility: Fundación Cenit Para La Investigación En Neurociencias
city: Mar Del Plata
country: Argentina
facility: Instituto de Investigaciones Clínicas Mar del Plata
city: Rosario
country: Argentina
facility: Sanatorio Parque
city: San Martín
country: Argentina
facility: Corporación Médica Sanatorio
city: Zárate
country: Argentina
facility: Instituto De Investigaciones Clinica Zarate
city: Brussels
country: Belgium
facility: Cohezio - Bruxelles
city: Brussel
country: Belgium
facility: Mensura
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Barranquilla
country: Colombia
facility: Clínica de la Costa
city: Bogotá
country: Colombia
facility: CAIMED - Bogota Clinical Research Center
city: Cali
country: Colombia
facility: Centro de Estudios en Infectología Pediátrica (CEIP)
city: Santo Domingo
country: Dominican Republic
facility: Fundacion Dominicana de Perinatologia Pro Bebe
city: Santo Domingo
country: Dominican Republic
facility: Instituto Dermatológico Dominicano y Cirugía de Piel Dr. Huberto Bogaert Díaz
city: Santo Domingo
country: Dominican Republic
facility: Clínica Cruz Jiminian
city: Santo Domingo
country: Dominican Republic
facility: Hospital General Regional Marcelino Vélez Santana
city: Köln
country: Germany
facility: Uniklinik Köln
city: München
country: Germany
facility: Ludwig-Maximilians-Universität München
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen - Institut für Tropenmedizin, Reisemedizin und Humanparasitologie
city: Ciudad de mexico
country: Mexico
facility: Instituto Nacional De Ciencias Medicas Y Nutricion Salvador Zubiran
city: Ciudad de mexico
country: Mexico
facility: CAIMED - México
city: Guadalajara
country: Mexico
facility: Panamerican Clinical research Mexico (Guadalajara)
city: Juriquilla
country: Mexico
facility: Panamerican Clinical Research Mexico S.A. DE C.V.
city: San Juan Del Río
country: Mexico
facility: Unidad de Medicina Especializada SMA
city: San Pedro Garza Garcia
country: Mexico
facility: Centro Medico Zambrano Hellion TecSalud
city: Alkmaar
country: Netherlands
facility: Noordwest Ziekenhuisgroep
city: Amsterdam
country: Netherlands
facility: Amsterdam Universitair Medische Centra - Academisch Medisch Centrum
city: Utrecht
country: Netherlands
facility: The Julius Center - Utrecht Science Park - Stratenum
city: Panama city
country: Panama
facility: Centro De Vacunacion Internacional - CEVAXIN Chorreras
city: Panama City
country: Panama
facility: Centro De Vacunacion Internacional - CEVAXIN 24 Diciembre
city: Panama city
country: Panama
facility: Centro de Vacunacion Internacional - CEVAXIN Avenida Mexico
city: Panamá
country: Panama
facility: Instituto de Investigaciones Científicas y Servicios de Alta Tecnología
city: Callao
country: Peru
facility: Centro de Investigaciones Tecnológicas, Biomédicas y Medioambientales
city: Chancay
country: Peru
facility: Hospital de Chancay y Servicios básicos de Salud
city: Ica
country: Peru
facility: Clinica Medica San Martin
city: Lima
country: Peru
facility: Instituto de Investigación Nutricional - Las Gardenias
city: Lima
country: Peru
facility: Instituto de Investigación Nutricional - San Carlos
city: Lima
country: Peru
facility: Instituto de Investigación Nutricional
city: Lima
country: Peru
facility: Asociación Civil Impacta Salud y Educación
city: Lima
country: Peru
facility: Centro de Investigación para ensayos Clínicos UPCH
city: Barakaldo
country: Spain
facility: OSI Eskerraldea-Enkarterri-Cruces/Hospital Universitario Cruces
city: Donostia-San Sebastián
country: Spain
facility: Hospital Universitario Donostia
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
Study officials:
References:
citation: 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.