A Study to Determine the Safety and Efficacy of SARS-CoV-2 mRNA Vaccine CVnCoV in Adults for COVID-19

Sponsor

CureVac AG (Industry)

Overall Status

Completed

CT.gov ID

NCT04652102

Collaborator

(none)

39,693

Enrollment

Locations

Arms

17.6

Actual Duration (Months)

862.9

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

The primary objective of the open-label phase of this trial is to evaluate safety in all participants ≥ 18 years of age remaining in the trial after unblinding.

Condition or Disease	Intervention/Treatment	Phase
Covid19 SARS-CoV-2	Biological: CVnCoV Biological: Placebo Biological: Authorized/licensed vaccines for preventing COVID-19 (AV)	Phase 2/Phase 3

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.).

Study Design

Study Type:

Interventional

Actual Enrollment :

39693 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Masking Description:

The randomized observer-blinded phases of this study are participant and investigator blinded. This is followed by an open-label phase.

Primary Purpose:

Prevention

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

Actual Study Start Date :

Dec 14, 2020

Actual Primary Completion Date :

Jun 3, 2022

Actual Study Completion Date :

Jun 3, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Biological: CVnCoV Intramuscular (IM) injection. Other Names: CV07050101
Placebo Comparator: 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.	Biological: Placebo Intramuscular (IM) injection.
Experimental: 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.	Biological: CVnCoV Intramuscular (IM) injection. Other Names: CV07050101
Placebo Comparator: 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.	Biological: Placebo Intramuscular (IM) injection.
Experimental: 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.	Biological: Authorized/licensed vaccines for preventing COVID-19 (AV) Intramuscular (IM) injection will be received as standard of care (SoC) outside the study.

Outcome Measures

Primary Outcome Measures

Number of participants who experience a first episode of virologically-confirmed {reverse transcription polymerase chain reaction (RT-PCR) positive} case of COVID-19 of any severity [Day 1 to Day 393]
Number of participants who experience one or more medically-attended adverse events (AEs) [Day 29 to Day 211]
Intensity grading of medically-attended adverse events (AEs) as per adapted Food and Drug Administration (FDA) classification [Day 29 to Day 211]
The adapted FDA classification will grade AEs on a grade of 0 to 3. Higher grades indicate a worse outcome.
Number of participants who experience one or more treatment-related medically-attended adverse events (AEs) [Day 29 to Day 211]
Number of participants who experience one or more serious adverse events (SAEs) [Day 1 to Day 393]
Intensity grading of serious adverse events (SAEs) as per adapted FDA classification [Day 1 to Day 393]
The adapted FDA classification will grade SAEs on a grade of 0 to 3. Higher grades indicate a worse outcome.
Number of participants who experience one or more treatment-related serious adverse events (SAEs) [Day 1 to Day 393]
Number of participants who experience one or more adverse events of special interest (AESI) [Day 1 to Day 393]
Intensity grading of adverse events of special interest (AESI) as per adapted FDA classification [Day 1 to Day 393]
The adapted FDA classification will grade AESI on a grade of 0 to 3. Higher grades indicate a worse outcome.
Number of participants who experience one or more treatment-related adverse events of special interest (AESI) [Day 1 to Day 393]
Number of participants who experience a fatal serious adverse event (SAE) [Day 1 to Day 393]
Number of participants who experience an adverse event (AE) leading to authorized/licensed vaccines withdrawal or trial discontinuation after first dose with an authorized/licensed vaccine for preventing COVID-19 (AV) administered [Day 1 to Day 393]
Measured in the open-label phase, Cohort A only.
Phase 2b participants only: Number of participants who experience one or more solicited local adverse events (AEs) [7 days after vaccination]
Phase 2b participants only: Intensity grading of solicited local adverse events (AEs) as per adapted FDA classification [7 days after vaccination]
The adapted FDA classification will grade AEs on a grade of 0 to 3. Higher grades indicate a worse outcome.
Phase 2b participants only: Duration of solicited local adverse events (AEs) [7 days after vaccination]
Phase 2b participants only: Number of participants who experience one or more solicited systemic adverse events (AE) [7 days after vaccination]
Phase 2b participants only: Intensity grading of solicited systemic adverse events (AEs) as per adapted FDA classification [7 days after vaccination]
The adapted FDA classification will grade AEs on a grade of 0 to 3. Higher grades indicate a worse outcome.
Phase 2b participants only: Duration of solicited systemic adverse events (AEs) [7 days after vaccination]
Phase 2b participants only: Number of participants who experience one or more unsolicited adverse events (AEs) [28 days after vaccination]
Phase 2b participants only: Intensity grading of unsolicited adverse events (AEs) as per adapted FDA classification [28 days after vaccination]
The adapted FDA classification will grade AEs on a grade of 0 to 3. Higher grades indicate a worse outcome.
Phase 2b participants only: Number of participants who experience one or more treatment-related unsolicited adverse events (AEs) [28 days after vaccination]
Number of participants who experience one or more adverse events (AEs) leading to vaccine withdrawal or trial discontinuation [Day 1 to Day 393]

Secondary Outcome Measures

Number of participants who experience a first episode of virologically-confirmed {reverse transcription polymerase chain reaction (RT-PCR) positive} moderate to severe case of COVID-19 [Day 1 to Day 393]
Number of participants who experience a first episode of virologically-confirmed {reverse transcription polymerase chain reaction (RT-PCR) positive} severe case of COVID-19 [Day 1 to Day 393]
Number of participants who experience a first episode of virologically-confirmed {reverse transcription polymerase chain reaction (RT-PCR) positive} case of COVID-19 of any severity due to infection with "wild type" and "UK" SARS-CoV-2 strains [Day 1 to Day 393]
Measured in SARS-CoV-2 naïve participants.
Number of participants aged ≥ 61 who experience a first episode of virologically-confirmed {reverse transcription polymerase chain reaction (RT-PCR) positive} case of COVID-19 of any severity [Day 1 to Day 393]
Number of participants who experience a virologically-confirmed {reverse transcription polymerase chain reaction (RT-PCR) positive} SARS-CoV-2 infection, with or without symptoms [Day 1 to Day 393]
Burden of disease (BoD) based on first episodes of virologically-confirmed {reverse transcription polymerase chain reaction (RT-PCR) positive} cases of COVID-19 [Day 1 to Day 393]
Number of participants who experience a virologically-confirmed {reverse transcription polymerase chain reaction (RT-PCR) positive} case of COVID-19 of any severity with symptom onset at any time after the first study vaccination [Post vaccination on Day 1 up to Day 393]
Number of participants with serum antibodies to SARS-CoV-2 spike (S) protein [Days 1, 29, 43, 120 and 211]
S protein will be measured by enzyme-linked immunosorbent assay (ELISA).
Number of participants who experience seroconversion to SARS-CoV-2 spike (S) protein [Days 1, 29, 43, 120 and 211]
S protein will be measured by enzyme-linked immunosorbent assay (ELISA). Seroconversion is defined as detectable SARS-CoV-2 S protein antibodies in the serum of participants who tested seronegative on Day 1.
Number of participants with serum vital neutralizing antibodies to SARS-CoV-2 virus [Days 1, 29, 43, 120 and 211]
Serum vital neutralizing antibodies to SARS-CoV-2 virus will be measured by a viral neutralizing antibody assay.
Number of participants who experience seroconversion to SARS-CoV-2 virus [Days 1, 29, 43, 120 and 211]
Seroconversion to SARS-CoV-2 virus will be measured by a viral neutralizing antibody assay. Seroconversion is defined as detectable SARS-CoV-2 viral neutralizing antibodies in the serum of participants who tested seronegative on Day 1.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

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.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Instituto de Investigaciones Clinicas Quilmes	Buenos Aires	Argentina	1878
2	Hospital Interzonal General Agudos Prof. Dr. Ramon Carrillo	Buenos Aires	Argentina	B1702FWM
3	Hospital Interzonal General de Agudos Vicente Lopez y Planes	Buenos Aires	Argentina	B1748
4	Hospital Zonal General de Agudos Descentralizado Evita Pueblo de Berazategui	Buenos Aires	Argentina	B1884LAD
5	Fundación Cenit Para La Investigación En Neurociencias	Buenos Aires	Argentina	C1125 ABD
6	Instituto de Investigaciones Clínicas Mar del Plata	Mar Del Plata	Argentina	B7600FZN
7	Sanatorio Parque	Rosario	Argentina	S2000
8	Corporación Médica Sanatorio	San Martín	Argentina	B1650CSQ
9	Instituto De Investigaciones Clinica Zarate	Zárate	Argentina	B2800DGH
10	Cohezio - Bruxelles	Brussels	Belgium	1000
11	Mensura	Brussel	Belgium	1030
12	Universitair Ziekenhuis Gent	Gent	Belgium	9000
13	Clínica de la Costa	Barranquilla	Colombia	80020
14	CAIMED - Bogota Clinical Research Center	Bogotá	Colombia	111621
15	Centro de Estudios en Infectología Pediátrica (CEIP)	Cali	Colombia	760042
16	Fundacion Dominicana de Perinatologia Pro Bebe	Santo Domingo	Dominican Republic	10204
17	Instituto Dermatológico Dominicano y Cirugía de Piel Dr. Huberto Bogaert Díaz	Santo Domingo	Dominican Republic	10305
18	Clínica Cruz Jiminian	Santo Domingo	Dominican Republic	10501
19	Hospital General Regional Marcelino Vélez Santana	Santo Domingo	Dominican Republic	11001
20	Uniklinik Köln	Köln	Germany	50937
21	Ludwig-Maximilians-Universität München	München	Germany	80802
22	Universitätsklinikum Tübingen - Institut für Tropenmedizin, Reisemedizin und Humanparasitologie	Tübingen	Germany	72074
23	Instituto Nacional De Ciencias Medicas Y Nutricion Salvador Zubiran	Ciudad de mexico	Mexico	14080
24	CAIMED - México	Ciudad de mexico	Mexico	6760
25	Panamerican Clinical research Mexico (Guadalajara)	Guadalajara	Mexico	44690
26	Panamerican Clinical Research Mexico S.A. DE C.V.	Juriquilla	Mexico	76226
27	Unidad de Medicina Especializada SMA	San Juan Del Río	Mexico	76800
28	Centro Medico Zambrano Hellion TecSalud	San Pedro Garza Garcia	Mexico	66278
29	Noordwest Ziekenhuisgroep	Alkmaar	Netherlands	1815JD
30	Amsterdam Universitair Medische Centra - Academisch Medisch Centrum	Amsterdam	Netherlands	1105 AZ
31	The Julius Center - Utrecht Science Park - Stratenum	Utrecht	Netherlands	3584 CX
32	Centro De Vacunacion Internacional - CEVAXIN Chorreras	Panama city	Panama	07064
33	Centro De Vacunacion Internacional - CEVAXIN 24 Diciembre	Panama City	Panama	07113
34	Centro de Vacunacion Internacional - CEVAXIN Avenida Mexico	Panama city	Panama	10662
35	Instituto de Investigaciones Científicas y Servicios de Alta Tecnología	Panamá	Panama	07097
36	Centro de Investigaciones Tecnológicas, Biomédicas y Medioambientales	Callao	Peru	07006
37	Hospital de Chancay y Servicios básicos de Salud	Chancay	Peru	15131
38	Clinica Medica San Martin	Ica	Peru	11000
39	Instituto de Investigación Nutricional - Las Gardenias	Lima	Peru	15024
40	Instituto de Investigación Nutricional - San Carlos	Lima	Peru	15024
41	Instituto de Investigación Nutricional	Lima	Peru	15024
42	Asociación Civil Impacta Salud y Educación	Lima	Peru	15063
43	Centro de Investigación para ensayos Clínicos UPCH	Lima	Peru	15102
44	OSI Eskerraldea-Enkarterri-Cruces/Hospital Universitario Cruces	Barakaldo	Spain	48903
45	Hospital Universitario Donostia	Donostia-San Sebastián	Spain	20014
46	Hospital Clínico San Carlos	Madrid	Spain	28040

Sponsors and Collaborators

CureVac AG

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

CureVac AG

ClinicalTrials.gov Identifier:

NCT04652102

Other Study ID Numbers:

CV-NCOV-004
2020-003998-22

First Posted:

Dec 3, 2020

Last Update Posted:

Jun 22, 2022

Last Verified:

Jun 1, 2022

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by CureVac AG

Vaccine

Additional relevant MeSH terms:

COVID-19

Study Results

No Results Posted as of Jun 22, 2022