Coronavirus, Covid19, SARS-CoV-2, Severe Acute Respiratory Syndrome
Conditions
Keywords
Vaccine, SARS, COVID, Safety, Immunogenicity
Brief summary
This study aims to evaluate the safety (in all participants) and reactogenicity (in a subset of participants) of CVnCoV administered as a 2-dose schedule to adult participants 18 years of age or older. The study also aims to assess antibody responses to the receptor-binding domain (RBD) of spike (S) protein of SARS-CoV-2 after 1 and 2 doses of CVnCoV in adults 18 years of age or older included in a subset of participants.
Interventions
BIOLOGICALCVnCoV Vaccine
Intramuscular injection
DRUGPlacebo
Intramuscular injection
Sponsors
German Federal Ministry of Education and Research
CureVac
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Male or female participants 18 years of age or older. * Health care workers (HCWs), employees or students in clinical training. * 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 urine pregnancy test (human chorionic gonadotropin 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 (IUDs); * Intrauterine hormone-releasing systems (IUSs); * Bilateral tubal ligation; * Vasectomized 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 SARS-CoV-2 infection or SARS-CoV-2 positive serology. * For females: pregnancy or lactation. * Use of any investigational or non-registered product (vaccine or drug) within 28 days preceding the administration of the first trial vaccine or planned use during the trial. * Receipt of licensed vaccines within 28 days (for live vaccines) or 14 days (for inactivated vaccines) prior to the administration of trial vaccine. * Prior administration of any investigational SARS-CoV-2 vaccine or other coronavirus (SARS-CoV, MERS-CoV) vaccine or planned use during the trial. * Any treatment with immunosuppressants or other immune-modifying drugs (including but not limited to 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), 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. * Active or chronic disease of, or currently on treatment for, hepatitis B virus (HBV) or hepatitis C virus (HCV). * History of angioedema (hereditary or idiopathic), or a history of any anaphylactic reaction. * History of Potential immune-mediated disease (pIMD). * History of allergy to any component of CVnCoV vaccine. * 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 un-controlled cardiovascular disease, gastrointestinal disease, liver disease, renal disease, respiratory disease, endocrine disorder, and neurological and psychiatric illnesses. * Participants with impaired coagulation or any bleeding disorder in whom an intramuscular (IM) injection or a blood draw is contraindicated. However, those with controlled and stable cases can be included in the trial. * Foreseeable non-compliance with protocol as judged by the Investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| SARS-CoV-2 RBD of Spike Protein Antibody (IgG) Levels on Days 1, 29 and 43 | Day 1, Day 29 and Day 43 | Titers of IgG antibodies directed against the SARS-CoV-2 RBD of Spike Protein antigen were measured by ELISA and expressed as geometric mean of titers (GMT) with 95% CI, by group. Individual values below the lower limit of quantification (LLOQ) were set to half of the LLOQ. Participants who tested positive for COVID-19 had their data included up to the point of a positive test result. Participants who received a licensed/authorized vaccine were censored at the day after receiving the licensed/authorized vaccine. |
| Intensity of Unsolicited AEs Per the Investigator's Assessment Occurring on the Day of Vaccination and the Following 28 Days After Any Dose | Day 1 to 28 days after Dose 2 (Day 57) | eDiaries were used for the collection of unsolicited AEs on each vaccination day and the following 28 days. The Investigator made an assessment of intensity for each AE reported during the trial and assigned it to one of the following categories: * Mild: an event that was easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities. * Moderate: an event that caused sufficient discomfort to interfere with normal everyday activities. * Severe: an event that prevented normal everyday activities. |
| Occurrence of Seroconversion for SARS-CoV-2 Receptor-Binding Domain (RBD) of Spike Protein Antibodies (IgG) on Day 29 and Day 43 | Baseline (Day 1), Day 29 and Day 43 | Titers of IgG antibodies directed against the SARS-CoV-2 RBD of Spike Protein antigen were measured by enzyme-linked immunosorbent assay (ELISA). Percentage with 95% confidence interval (CI) of participants for whom a seroconversion was observed is presented by group. Seroconversion was defined as a fold increase above 1 in SARS-CoV-2 Spike Protein RBD IgG antibody levels in participants seronegative at Baseline. Participants who tested positive for COVID-19 had their data included up to the point of a positive test result. Participants who received a licensed/authorized vaccine were censored at the day after receiving the licensed/authorized vaccine. |
| Number of Participants Who Experienced a Medically Attended Adverse Event (AE) Occurring in the Following 6 Months After Dose 2 | Up to 6 months after Dose 2 (Days 29 to 211) | Medically attended AEs were defined as AEs with medically attended visits that are 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. The Investigator assessed the relationship between trial vaccine and occurrence of each AE. |
| Number of Participants Who Experienced a Serious Adverse Event (SAE) | Day 1 to Day 393 | 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 AE. |
| Intensity of SAEs Per the Investigator's Assessment | Day 1 to Day 393 | 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 for each AE reported during the trial and assigned it to one of the following categories: * Mild: an event that was easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities. * Moderate: an event that caused sufficient discomfort to interfere with normal everyday activities. * Severe: an event that prevented normal everyday activities. |
| Number of Participants Who Experienced an Adverse Event of Special Interest (AESI) Occurring in the Following 1 Year After Dose 2 | Up to 1 year after Dose 2 (Days 29 to 393) | The following events were considered and collected as AESI throughout the trial: * AEs with a suspected immune-mediated etiology. * Other AEs relevant to SARS-CoV-2 vaccine development or the target disease. * COVID-19. The Investigator assessed the relationship between trial vaccine and occurrence of each AE. |
| Number of Participants Who Experienced Death Due to SAE | Day 1 to Day 393 | 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. |
| Number of Participants Who Experienced an AE Leading to Vaccine Withdrawal Occurring in the Following 1 Year After Dose 2 | Up to 1 year after Dose 2 (Days 29 to 393) | — |
| Number of Participants Who Experienced an AE Leading to Trial Discontinuation Occurring in the Following 1 Year After Dose 2 | Up to 1 year after Dose 2 (Days 29 to 393) | — |
| Number of Participants Who Experienced an Unsolicited AE Occurring on the Day of Vaccination and the Following 28 Days After Any Dose | Day 1 to 28 days after Dose 2 (Day 57) | eDiaries were used for the collection of unsolicited AEs on each vaccination day and the following 28 days. The Investigator assessed the relationship between trial vaccine and occurrence of each AE. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| SARS-CoV-2 Neutralizing Antibody Levels on Days 1, 29 and 43 | Day 1, Day 29 and Day 43 | Neutralizing activity of induced antibodies was determined by an activity assay. GMT with 95% CI of SARS-CoV-2 neutralizing antibody levels is presented by group. Individual values below the LLOQ were set to half of the LLOQ. Participants who tested positive for COVID-19 had their data included up to the point of a positive test result. Participants who received a licensed/authorized vaccine were censored at the day after receiving the licensed/authorized vaccine. |
| Occurrence of Seroconversion for SARS-CoV-2 Neutralizing Antibodies on Day 29 and Day 43 | Baseline (Day 1), Day 29 and Day 43 | Neutralizing activity of induced antibodies was determined by an activity assay. Percentage with 95% CI of participants for whom a seroconversion was observed is presented by group. Seroconversion was defined as a fold increase above 1 in SARS-CoV-2 neutralizing antibody levels in participants seronegative at Baseline. Participants who tested positive for COVID-19 had their data included up to the point of a positive test result. Participants who received a licensed/authorized vaccine were censored at the day after receiving the licensed/authorized vaccine. |
Countries
Germany
Participant flow
Recruitment details
This trial was performed in Germany between 23 December 2020 and 08 June 2022.
Pre-assignment details
Of the 2357 participants who were randomized, 2351 participants were treated.
Participants by arm
| Arm | Count |
|---|---|
| CVnCoV: Group 1, Lot 1 Participants in Group 1 were vaccinated with CVnCoV 12 µg Lot 1 as an intramuscular injection by needle in the deltoid area on Day 1 and Day 29. | 783 |
| CVnCoV: Group 2, Lot 2 Participants in Group 2 were vaccinated with CVnCoV 12 µg Lot 2 as an intramuscular injection by needle in the deltoid area on Day 1 and Day 29. | 785 |
| Placebo Participants received a placebo as an intramuscular injection by needle in the deltoid area on Day 1 and Day 29. | 783 |
| Total | 2,351 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 |
| Overall Study | Did Not Receive Treatment | 3 | 1 | 2 |
| Overall Study | Lost to Follow-up | 55 | 53 | 44 |
| Overall Study | Miscellaneous | 27 | 23 | 207 |
| Overall Study | Physician Decision | 1 | 0 | 0 |
| Overall Study | Received Alternative Authorized Vaccine | 0 | 1 | 17 |
| Overall Study | Withdrawal by Participant | 83 | 71 | 142 |
Baseline characteristics
| Characteristic | CVnCoV: Group 1, Lot 1 | Placebo | Total | CVnCoV: Group 2, Lot 2 |
|---|---|---|---|---|
| Age, Continuous | 42.2 years STANDARD_DEVIATION 14.88 | 42.7 years STANDARD_DEVIATION 14.52 | 42.7 years STANDARD_DEVIATION 14.73 | 43.4 years STANDARD_DEVIATION 14.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 4 Participants | 14 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 764 Participants | 758 Participants | 2281 Participants | 759 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 14 Participants | 21 Participants | 56 Participants | 21 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 13 Participants | 14 Participants | 36 Participants | 9 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 0 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 2 Participants | 0 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 4 Participants | 5 Participants | 12 Participants | 3 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 7 Participants | 4 Participants | 17 Participants | 6 Participants |
| Race/Ethnicity, Customized White | 755 Participants | 760 Participants | 2280 Participants | 765 Participants |
| Sex: Female, Male Female | 527 Participants | 521 Participants | 1587 Participants | 539 Participants |
| Sex: Female, Male Male | 256 Participants | 262 Participants | 764 Participants | 246 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 783 | 0 / 785 | 1 / 783 |
| other Total, other adverse events | 542 / 783 | 547 / 785 | 475 / 783 |
| serious Total, serious adverse events | 8 / 783 | 10 / 785 | 6 / 783 |
Outcome results
Primary
Intensity of SAEs Per the Investigator's 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 for each AE reported during the trial and assigned it to one of the following categories: * Mild: an event that was easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities. * Moderate: an event that caused sufficient discomfort to interfere with normal everyday activities. * Severe: an event that prevented normal everyday activities.
Time frame: Day 1 to Day 393
Population: Safety Analysis Set: All participants randomized in the trial who received at least one dose of any lot of CVnCoV or placebo vaccine.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CVnCoV: Group 1, Lot 1 | Intensity of SAEs Per the Investigator's Assessment | Any moderate SAEs | 2 Participants |
| CVnCoV: Group 1, Lot 1 | Intensity of SAEs Per the Investigator's Assessment | Any mild SAEs | 0 Participants |
| CVnCoV: Group 1, Lot 1 | Intensity of SAEs Per the Investigator's Assessment | Any severe SAEs | 6 Participants |
| CVnCoV: Group 2, Lot 2 | Intensity of SAEs Per the Investigator's Assessment | Any moderate SAEs | 5 Participants |
| CVnCoV: Group 2, Lot 2 | Intensity of SAEs Per the Investigator's Assessment | Any mild SAEs | 0 Participants |
| CVnCoV: Group 2, Lot 2 | Intensity of SAEs Per the Investigator's Assessment | Any severe SAEs | 5 Participants |
| Placebo | Intensity of SAEs Per the Investigator's Assessment | Any mild SAEs | 0 Participants |
| Placebo | Intensity of SAEs Per the Investigator's Assessment | Any severe SAEs | 5 Participants |
| Placebo | Intensity of SAEs Per the Investigator's Assessment | Any moderate SAEs | 1 Participants |
Primary
Intensity of Unsolicited AEs Per the Investigator's Assessment Occurring on the Day of Vaccination and the Following 28 Days After Any Dose
eDiaries were used for the collection of unsolicited AEs on each vaccination day and the following 28 days. The Investigator made an assessment of intensity for each AE reported during the trial and assigned it to one of the following categories: * Mild: an event that was easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities. * Moderate: an event that caused sufficient discomfort to interfere with normal everyday activities. * Severe: an event that prevented normal everyday activities.
Time frame: Day 1 to 28 days after Dose 2 (Day 57)
Population: Safety Analysis Subset: The first 1289 participants enrolled who belong to the Safety Analysis Set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CVnCoV: Group 1, Lot 1 | Intensity of Unsolicited AEs Per the Investigator's Assessment Occurring on the Day of Vaccination and the Following 28 Days After Any Dose | Any severe unsolicited AEs | 14 Participants |
| CVnCoV: Group 1, Lot 1 | Intensity of Unsolicited AEs Per the Investigator's Assessment Occurring on the Day of Vaccination and the Following 28 Days After Any Dose | Any unsolicited AEs without intensity assessment | 25 Participants |
| CVnCoV: Group 1, Lot 1 | Intensity of Unsolicited AEs Per the Investigator's Assessment Occurring on the Day of Vaccination and the Following 28 Days After Any Dose | Any mild unsolicited AEs | 133 Participants |
| CVnCoV: Group 1, Lot 1 | Intensity of Unsolicited AEs Per the Investigator's Assessment Occurring on the Day of Vaccination and the Following 28 Days After Any Dose | Any moderate unsolicited AEs | 73 Participants |
| CVnCoV: Group 2, Lot 2 | Intensity of Unsolicited AEs Per the Investigator's Assessment Occurring on the Day of Vaccination and the Following 28 Days After Any Dose | Any severe unsolicited AEs | 28 Participants |
| CVnCoV: Group 2, Lot 2 | Intensity of Unsolicited AEs Per the Investigator's Assessment Occurring on the Day of Vaccination and the Following 28 Days After Any Dose | Any moderate unsolicited AEs | 71 Participants |
| CVnCoV: Group 2, Lot 2 | Intensity of Unsolicited AEs Per the Investigator's Assessment Occurring on the Day of Vaccination and the Following 28 Days After Any Dose | Any unsolicited AEs without intensity assessment | 22 Participants |
| CVnCoV: Group 2, Lot 2 | Intensity of Unsolicited AEs Per the Investigator's Assessment Occurring on the Day of Vaccination and the Following 28 Days After Any Dose | Any mild unsolicited AEs | 149 Participants |
| Placebo | Intensity of Unsolicited AEs Per the Investigator's Assessment Occurring on the Day of Vaccination and the Following 28 Days After Any Dose | Any unsolicited AEs without intensity assessment | 21 Participants |
| Placebo | Intensity of Unsolicited AEs Per the Investigator's Assessment Occurring on the Day of Vaccination and the Following 28 Days After Any Dose | Any mild unsolicited AEs | 114 Participants |
| Placebo | Intensity of Unsolicited AEs Per the Investigator's Assessment Occurring on the Day of Vaccination and the Following 28 Days After Any Dose | Any moderate unsolicited AEs | 42 Participants |
| Placebo | Intensity of Unsolicited AEs Per the Investigator's Assessment Occurring on the Day of Vaccination and the Following 28 Days After Any Dose | Any severe unsolicited AEs | 10 Participants |
Primary
Number of Participants Who Experienced a Medically Attended Adverse Event (AE) Occurring in the Following 6 Months After Dose 2
Medically attended AEs were defined as AEs with medically attended visits that are 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. The Investigator assessed the relationship between trial vaccine and occurrence of each AE.
Time frame: Up to 6 months after Dose 2 (Days 29 to 211)
Population: Safety Analysis Set: All participants randomized in the trial who received at least one dose of any lot of CVnCoV or placebo vaccine.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CVnCoV: Group 1, Lot 1 | Number of Participants Who Experienced a Medically Attended Adverse Event (AE) Occurring in the Following 6 Months After Dose 2 | Any medically attended AEs | 95 Participants |
| CVnCoV: Group 1, Lot 1 | Number of Participants Who Experienced a Medically Attended Adverse Event (AE) Occurring in the Following 6 Months After Dose 2 | Any related medically attended AEs | 34 Participants |
| CVnCoV: Group 2, Lot 2 | Number of Participants Who Experienced a Medically Attended Adverse Event (AE) Occurring in the Following 6 Months After Dose 2 | Any medically attended AEs | 133 Participants |
| CVnCoV: Group 2, Lot 2 | Number of Participants Who Experienced a Medically Attended Adverse Event (AE) Occurring in the Following 6 Months After Dose 2 | Any related medically attended AEs | 32 Participants |
| Placebo | Number of Participants Who Experienced a Medically Attended Adverse Event (AE) Occurring in the Following 6 Months After Dose 2 | Any medically attended AEs | 58 Participants |
| Placebo | Number of Participants Who Experienced a Medically Attended Adverse Event (AE) Occurring in the Following 6 Months After Dose 2 | Any related medically attended AEs | 13 Participants |
Primary
Number of Participants Who Experienced an Adverse Event of Special Interest (AESI) Occurring in the Following 1 Year After Dose 2
The following events were considered and collected as AESI throughout the trial: * AEs with a suspected immune-mediated etiology. * Other AEs relevant to SARS-CoV-2 vaccine development or the target disease. * COVID-19. The Investigator assessed the relationship between trial vaccine and occurrence of each AE.
Time frame: Up to 1 year after Dose 2 (Days 29 to 393)
Population: Safety Analysis Set: All participants randomized in the trial who received at least one dose of any lot of CVnCoV or placebo vaccine.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CVnCoV: Group 1, Lot 1 | Number of Participants Who Experienced an Adverse Event of Special Interest (AESI) Occurring in the Following 1 Year After Dose 2 | Any AESIs | 14 Participants |
| CVnCoV: Group 1, Lot 1 | Number of Participants Who Experienced an Adverse Event of Special Interest (AESI) Occurring in the Following 1 Year After Dose 2 | Any related AESIs | 7 Participants |
| CVnCoV: Group 2, Lot 2 | Number of Participants Who Experienced an Adverse Event of Special Interest (AESI) Occurring in the Following 1 Year After Dose 2 | Any AESIs | 14 Participants |
| CVnCoV: Group 2, Lot 2 | Number of Participants Who Experienced an Adverse Event of Special Interest (AESI) Occurring in the Following 1 Year After Dose 2 | Any related AESIs | 5 Participants |
| Placebo | Number of Participants Who Experienced an Adverse Event of Special Interest (AESI) Occurring in the Following 1 Year After Dose 2 | Any AESIs | 5 Participants |
| Placebo | Number of Participants Who Experienced an Adverse Event of Special Interest (AESI) Occurring in the Following 1 Year After Dose 2 | Any related AESIs | 0 Participants |
Primary
Number of Participants Who Experienced an AE Leading to Trial Discontinuation Occurring in the Following 1 Year After Dose 2
Time frame: Up to 1 year after Dose 2 (Days 29 to 393)
Population: Safety Analysis Set: All participants randomized in the trial who received at least one dose of any lot of CVnCoV or placebo vaccine.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CVnCoV: Group 1, Lot 1 | Number of Participants Who Experienced an AE Leading to Trial Discontinuation Occurring in the Following 1 Year After Dose 2 | 1 Participants |
| CVnCoV: Group 2, Lot 2 | Number of Participants Who Experienced an AE Leading to Trial Discontinuation Occurring in the Following 1 Year After Dose 2 | 0 Participants |
| Placebo | Number of Participants Who Experienced an AE Leading to Trial Discontinuation Occurring in the Following 1 Year After Dose 2 | 1 Participants |
Primary
Number of Participants Who Experienced an AE Leading to Vaccine Withdrawal Occurring in the Following 1 Year After Dose 2
Time frame: Up to 1 year after Dose 2 (Days 29 to 393)
Population: Safety Analysis Set: All participants randomized in the trial who received at least one dose of any lot of CVnCoV or placebo vaccine.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CVnCoV: Group 1, Lot 1 | Number of Participants Who Experienced an AE Leading to Vaccine Withdrawal Occurring in the Following 1 Year After Dose 2 | 7 Participants |
| CVnCoV: Group 2, Lot 2 | Number of Participants Who Experienced an AE Leading to Vaccine Withdrawal Occurring in the Following 1 Year After Dose 2 | 5 Participants |
| Placebo | Number of Participants Who Experienced an AE Leading to Vaccine Withdrawal Occurring in the Following 1 Year After Dose 2 | 2 Participants |
Primary
Number of Participants Who Experienced an Unsolicited AE Occurring on the Day of Vaccination and the Following 28 Days After Any Dose
eDiaries were used for the collection of unsolicited AEs on each vaccination day and the following 28 days. The Investigator assessed the relationship between trial vaccine and occurrence of each AE.
Time frame: Day 1 to 28 days after Dose 2 (Day 57)
Population: Safety Analysis Subset: The first 1289 participants enrolled who belong to the Safety Analysis Set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CVnCoV: Group 1, Lot 1 | Number of Participants Who Experienced an Unsolicited AE Occurring on the Day of Vaccination and the Following 28 Days After Any Dose | Any unsolicited AEs | 245 Participants |
| CVnCoV: Group 1, Lot 1 | Number of Participants Who Experienced an Unsolicited AE Occurring on the Day of Vaccination and the Following 28 Days After Any Dose | Any related unsolicited AEs | 183 Participants |
| CVnCoV: Group 2, Lot 2 | Number of Participants Who Experienced an Unsolicited AE Occurring on the Day of Vaccination and the Following 28 Days After Any Dose | Any unsolicited AEs | 270 Participants |
| CVnCoV: Group 2, Lot 2 | Number of Participants Who Experienced an Unsolicited AE Occurring on the Day of Vaccination and the Following 28 Days After Any Dose | Any related unsolicited AEs | 186 Participants |
| Placebo | Number of Participants Who Experienced an Unsolicited AE Occurring on the Day of Vaccination and the Following 28 Days After Any Dose | Any unsolicited AEs | 187 Participants |
| Placebo | Number of Participants Who Experienced an Unsolicited AE Occurring on the Day of Vaccination and the Following 28 Days After Any Dose | Any related unsolicited AEs | 88 Participants |
Primary
Number of Participants Who Experienced a Serious Adverse Event (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 AE.
Time frame: Day 1 to Day 393
Population: Safety Analysis Set: All participants randomized in the trial who received at least one dose of any lot of CVnCoV or placebo vaccine.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CVnCoV: Group 1, Lot 1 | Number of Participants Who Experienced a Serious Adverse Event (SAE) | Any SAEs | 8 Participants |
| CVnCoV: Group 1, Lot 1 | Number of Participants Who Experienced a Serious Adverse Event (SAE) | Any related SAEs | 1 Participants |
| CVnCoV: Group 2, Lot 2 | Number of Participants Who Experienced a Serious Adverse Event (SAE) | Any SAEs | 10 Participants |
| CVnCoV: Group 2, Lot 2 | Number of Participants Who Experienced a Serious Adverse Event (SAE) | Any related SAEs | 1 Participants |
| Placebo | Number of Participants Who Experienced a Serious Adverse Event (SAE) | Any SAEs | 6 Participants |
| Placebo | Number of Participants Who Experienced a Serious Adverse Event (SAE) | Any related SAEs | 0 Participants |
Primary
Number of Participants Who Experienced Death Due to 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.
Time frame: Day 1 to Day 393
Population: Safety Analysis Set: All participants randomized in the trial who received at least one dose of any lot of CVnCoV or placebo vaccine.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CVnCoV: Group 1, Lot 1 | Number of Participants Who Experienced Death Due to SAE | 0 Participants |
| CVnCoV: Group 2, Lot 2 | Number of Participants Who Experienced Death Due to SAE | 0 Participants |
| Placebo | Number of Participants Who Experienced Death Due to SAE | 0 Participants |
Primary
Occurrence of Seroconversion for SARS-CoV-2 Receptor-Binding Domain (RBD) of Spike Protein Antibodies (IgG) on Day 29 and Day 43
Titers of IgG antibodies directed against the SARS-CoV-2 RBD of Spike Protein antigen were measured by enzyme-linked immunosorbent assay (ELISA). Percentage with 95% confidence interval (CI) of participants for whom a seroconversion was observed is presented by group. Seroconversion was defined as a fold increase above 1 in SARS-CoV-2 Spike Protein RBD IgG antibody levels in participants seronegative at Baseline. Participants who tested positive for COVID-19 had their data included up to the point of a positive test result. Participants who received a licensed/authorized vaccine were censored at the day after receiving the licensed/authorized vaccine.
Time frame: Baseline (Day 1), Day 29 and Day 43
Population: Per Protocol Immunogenicity Set: 250 participants who received both doses as randomized and within the windows defined in the protocol, had no major protocol deviations expected to impact the immunogenicity outcomes, and had not received medical treatments that may interfere with any of the immunogenicity measurements. Only participants seronegative at Baseline with evaluable samples at each visit are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CVnCoV: Group 1, Lot 1 | Occurrence of Seroconversion for SARS-CoV-2 Receptor-Binding Domain (RBD) of Spike Protein Antibodies (IgG) on Day 29 and Day 43 | Day 29 | 8.1 percentage of participants |
| CVnCoV: Group 1, Lot 1 | Occurrence of Seroconversion for SARS-CoV-2 Receptor-Binding Domain (RBD) of Spike Protein Antibodies (IgG) on Day 29 and Day 43 | Day 43 | 95.5 percentage of participants |
| CVnCoV: Group 2, Lot 2 | Occurrence of Seroconversion for SARS-CoV-2 Receptor-Binding Domain (RBD) of Spike Protein Antibodies (IgG) on Day 29 and Day 43 | Day 43 | 94.2 percentage of participants |
| CVnCoV: Group 2, Lot 2 | Occurrence of Seroconversion for SARS-CoV-2 Receptor-Binding Domain (RBD) of Spike Protein Antibodies (IgG) on Day 29 and Day 43 | Day 29 | 18.4 percentage of participants |
| Placebo | Occurrence of Seroconversion for SARS-CoV-2 Receptor-Binding Domain (RBD) of Spike Protein Antibodies (IgG) on Day 29 and Day 43 | Day 29 | 13.2 percentage of participants |
| Placebo | Occurrence of Seroconversion for SARS-CoV-2 Receptor-Binding Domain (RBD) of Spike Protein Antibodies (IgG) on Day 29 and Day 43 | Day 43 | 94.8 percentage of participants |
| Placebo | Occurrence of Seroconversion for SARS-CoV-2 Receptor-Binding Domain (RBD) of Spike Protein Antibodies (IgG) on Day 29 and Day 43 | Day 29 | 0.0 percentage of participants |
| Placebo | Occurrence of Seroconversion for SARS-CoV-2 Receptor-Binding Domain (RBD) of Spike Protein Antibodies (IgG) on Day 29 and Day 43 | Day 43 | 0.0 percentage of participants |
Primary
SARS-CoV-2 RBD of Spike Protein Antibody (IgG) Levels on Days 1, 29 and 43
Titers of IgG antibodies directed against the SARS-CoV-2 RBD of Spike Protein antigen were measured by ELISA and expressed as geometric mean of titers (GMT) with 95% CI, by group. Individual values below the lower limit of quantification (LLOQ) were set to half of the LLOQ. Participants who tested positive for COVID-19 had their data included up to the point of a positive test result. Participants who received a licensed/authorized vaccine were censored at the day after receiving the licensed/authorized vaccine.
Time frame: Day 1, Day 29 and Day 43
Population: Per Protocol Immunogenicity Set: 250 participants who received both doses as randomized and within the windows defined in the protocol, had no major protocol deviations expected to impact the immunogenicity outcomes, and had not received medical treatments that may interfere with any of the immunogenicity measurements. Only participants seronegative at Baseline with evaluable samples at each visit are included.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| CVnCoV: Group 1, Lot 1 | SARS-CoV-2 RBD of Spike Protein Antibody (IgG) Levels on Days 1, 29 and 43 | Day 1 | 50.000 GMT |
| CVnCoV: Group 1, Lot 1 | SARS-CoV-2 RBD of Spike Protein Antibody (IgG) Levels on Days 1, 29 and 43 | Day 43 | 1285.722 GMT |
| CVnCoV: Group 1, Lot 1 | SARS-CoV-2 RBD of Spike Protein Antibody (IgG) Levels on Days 1, 29 and 43 | Day 29 | 55.145 GMT |
| CVnCoV: Group 2, Lot 2 | SARS-CoV-2 RBD of Spike Protein Antibody (IgG) Levels on Days 1, 29 and 43 | Day 1 | 50.000 GMT |
| CVnCoV: Group 2, Lot 2 | SARS-CoV-2 RBD of Spike Protein Antibody (IgG) Levels on Days 1, 29 and 43 | Day 43 | 1151.416 GMT |
| CVnCoV: Group 2, Lot 2 | SARS-CoV-2 RBD of Spike Protein Antibody (IgG) Levels on Days 1, 29 and 43 | Day 29 | 62.236 GMT |
| Placebo | SARS-CoV-2 RBD of Spike Protein Antibody (IgG) Levels on Days 1, 29 and 43 | Day 29 | 58.566 GMT |
| Placebo | SARS-CoV-2 RBD of Spike Protein Antibody (IgG) Levels on Days 1, 29 and 43 | Day 1 | 50.000 GMT |
| Placebo | SARS-CoV-2 RBD of Spike Protein Antibody (IgG) Levels on Days 1, 29 and 43 | Day 43 | 1217.489 GMT |
| Placebo | SARS-CoV-2 RBD of Spike Protein Antibody (IgG) Levels on Days 1, 29 and 43 | Day 1 | 50.000 GMT |
| Placebo | SARS-CoV-2 RBD of Spike Protein Antibody (IgG) Levels on Days 1, 29 and 43 | Day 43 | 50.000 GMT |
| Placebo | SARS-CoV-2 RBD of Spike Protein Antibody (IgG) Levels on Days 1, 29 and 43 | Day 29 | 50.000 GMT |
Secondary
Occurrence of Seroconversion for SARS-CoV-2 Neutralizing Antibodies on Day 29 and Day 43
Neutralizing activity of induced antibodies was determined by an activity assay. Percentage with 95% CI of participants for whom a seroconversion was observed is presented by group. Seroconversion was defined as a fold increase above 1 in SARS-CoV-2 neutralizing antibody levels in participants seronegative at Baseline. Participants who tested positive for COVID-19 had their data included up to the point of a positive test result. Participants who received a licensed/authorized vaccine were censored at the day after receiving the licensed/authorized vaccine.
Time frame: Baseline (Day 1), Day 29 and Day 43
Population: Per Protocol Immunogenicity Set: 250 participants who received both doses as randomized and within the windows defined in the protocol, had no major protocol deviations expected to impact the immunogenicity outcomes, and had not received medical treatments that may interfere with any of the immunogenicity measurements. Only participants seronegative at Baseline with evaluable samples at each visit are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CVnCoV: Group 1, Lot 1 | Occurrence of Seroconversion for SARS-CoV-2 Neutralizing Antibodies on Day 29 and Day 43 | Day 29 | 2.0 percentage of participants |
| CVnCoV: Group 1, Lot 1 | Occurrence of Seroconversion for SARS-CoV-2 Neutralizing Antibodies on Day 29 and Day 43 | Day 43 | 76.1 percentage of participants |
| CVnCoV: Group 2, Lot 2 | Occurrence of Seroconversion for SARS-CoV-2 Neutralizing Antibodies on Day 29 and Day 43 | Day 43 | 75.6 percentage of participants |
| CVnCoV: Group 2, Lot 2 | Occurrence of Seroconversion for SARS-CoV-2 Neutralizing Antibodies on Day 29 and Day 43 | Day 29 | 2.0 percentage of participants |
| Placebo | Occurrence of Seroconversion for SARS-CoV-2 Neutralizing Antibodies on Day 29 and Day 43 | Day 29 | 2.0 percentage of participants |
| Placebo | Occurrence of Seroconversion for SARS-CoV-2 Neutralizing Antibodies on Day 29 and Day 43 | Day 43 | 75.9 percentage of participants |
| Placebo | Occurrence of Seroconversion for SARS-CoV-2 Neutralizing Antibodies on Day 29 and Day 43 | Day 29 | 0.0 percentage of participants |
| Placebo | Occurrence of Seroconversion for SARS-CoV-2 Neutralizing Antibodies on Day 29 and Day 43 | Day 43 | 0.0 percentage of participants |
Secondary
SARS-CoV-2 Neutralizing Antibody Levels on Days 1, 29 and 43
Neutralizing activity of induced antibodies was determined by an activity assay. GMT with 95% CI of SARS-CoV-2 neutralizing antibody levels is presented by group. Individual values below the LLOQ were set to half of the LLOQ. Participants who tested positive for COVID-19 had their data included up to the point of a positive test result. Participants who received a licensed/authorized vaccine were censored at the day after receiving the licensed/authorized vaccine.
Time frame: Day 1, Day 29 and Day 43
Population: Per Protocol Immunogenicity Set: 250 participants who received both doses as randomized and within the windows defined in the protocol, had no major protocol deviations expected to impact the immunogenicity outcomes, and had not received medical treatments that may interfere with any of the immunogenicity measurements. Only participants seronegative at Baseline with evaluable samples at each visit are included.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| CVnCoV: Group 1, Lot 1 | SARS-CoV-2 Neutralizing Antibody Levels on Days 1, 29 and 43 | Day 43 | 28.846 GMT |
| CVnCoV: Group 1, Lot 1 | SARS-CoV-2 Neutralizing Antibody Levels on Days 1, 29 and 43 | Day 1 | 5.000 GMT |
| CVnCoV: Group 1, Lot 1 | SARS-CoV-2 Neutralizing Antibody Levels on Days 1, 29 and 43 | Day 29 | 5.160 GMT |
| CVnCoV: Group 2, Lot 2 | SARS-CoV-2 Neutralizing Antibody Levels on Days 1, 29 and 43 | Day 43 | 23.976 GMT |
| CVnCoV: Group 2, Lot 2 | SARS-CoV-2 Neutralizing Antibody Levels on Days 1, 29 and 43 | Day 29 | 5.071 GMT |
| CVnCoV: Group 2, Lot 2 | SARS-CoV-2 Neutralizing Antibody Levels on Days 1, 29 and 43 | Day 1 | 5.000 GMT |
| Placebo | SARS-CoV-2 Neutralizing Antibody Levels on Days 1, 29 and 43 | Day 1 | 5.000 GMT |
| Placebo | SARS-CoV-2 Neutralizing Antibody Levels on Days 1, 29 and 43 | Day 29 | 5.116 GMT |
| Placebo | SARS-CoV-2 Neutralizing Antibody Levels on Days 1, 29 and 43 | Day 43 | 26.327 GMT |
| Placebo | SARS-CoV-2 Neutralizing Antibody Levels on Days 1, 29 and 43 | Day 43 | 5.000 GMT |
| Placebo | SARS-CoV-2 Neutralizing Antibody Levels on Days 1, 29 and 43 | Day 1 | 5.000 GMT |
| Placebo | SARS-CoV-2 Neutralizing Antibody Levels on Days 1, 29 and 43 | Day 29 | 5.000 GMT |