The primary objectives of this study are to evaluate the safety and reactogenicity profile after 1 and 2 dose administrations of investigational SARS-CoV-2 mRNA vaccine CVnCoV, and to evaluate the humoral immune responses 14 days after 2 dose administrations of CVnCoV.
Study participants with the following mild to moderate per protocol defined co-morbidities will be recruited: chronic kidney disease (CKD); cardiovascular disease (CVD), chronic obstructive pulmonary disease (COPD), type-2-diabetes. After safety data review, recruitment for severe cases will be opened. No severity classification will be done for study participants with chronic human immunodeficiency virus (HIV) infection with stable aviremia 12 months prior enrollment, for renal transplant patients if stable under medication for at least 6 months prior enrollment, and for study participants with a body mass index \> 32 kg/m\^2. 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 Type
INTERVENTIONAL
Allocation
NA
Purpose
PREVENTION
Masking
NONE
Enrollment
129
Intramuscular (IM) injection in the deltoid area, preferably in the non-dominant arm.
Centre Hospitalier Universitaire Saint-Pierre
Brussels, Belgium
Université Libre de Bruxelles (ULB) - Hopital Erasme
Brussels, Belgium
Universite Catholique de Louvain (UCL) - Cliniques Universitaires Saint-Luc
Brussels, Belgium
Centre Hospitalier Universitaire (CHU) de Liege - Domaine Universitaire du Sart Tilman
Liège, Belgium
Number of Participants Who Experienced a Solicited Adverse Event (AE) Occurring on the Day of Vaccination and the Following 7 Days After Any Dose
Reactogenicity was assessed daily via collection of solicited local AEs (injection site pain, redness, swelling, and itching) and solicited systemic AEs (fever, headache, fatigue, chills, myalgia, arthralgia, nausea/vomiting, and diarrhea) using paper diary cards. By definition, all solicited local AEs occurring from the time of first vaccination were considered related to trial vaccination. For solicited systemic AEs, the Investigator assessed the relationship between trial vaccine and each occurrence of each AE.
Time frame: Up to 7 days after vaccination (Days 1 to 8 and Days 29 to 36)
Intensity of Solicited AEs Per US Food and Drug Administration (FDA) Toxicity Grading Scale Occurring on the Day of Vaccination and the Following 7 Days After Any Dose
Reactogenicity was assessed daily via collection of solicited local AEs (injection site pain, redness, swelling, and itching) and solicited systemic AEs (fever, headache, fatigue, chills, myalgia, arthralgia, nausea/vomiting, and diarrhea) using paper diary cards. Intensity of solicited local AEs and solicited systemic AEs were graded per the FDA Toxicity Grading Scale at Grades 1-3, where higher grades indicate a worse outcome.
Time frame: Up to 7 days after vaccination (Days 1 to 8 and Days 29 to 36)
Duration of Solicited AEs Occurring on the Day of Vaccination and the Following 7 Days After Any Dose
Reactogenicity was assessed daily via collection of solicited local AEs (injection site pain, redness, swelling, and itching) and solicited systemic AEs (fever, headache, fatigue, chills, myalgia, arthralgia, nausea/vomiting, and diarrhea) using paper diary cards. Duration was calculated as consecutive days with a respective solicited AE regardless of the grade of the AE. AEs ongoing after Day 8 were included.
Time frame: Up to 7 days after vaccination (Days 1 to 8 and Days 29 to 36)
Number of Participants Who Experienced an Unsolicited AE Occurring on the Day of Vaccination and the Following 28 Days After Any Dose
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Diaries were used for collection of unsolicited AEs on each vaccination day and the following 28 days. In addition, participants were contacted by phone to verify whether they had any health concerns since the last visit. The Investigator assessed the relationship between trial vaccine and each occurrence of each AE.
Time frame: Up to 28 days after vaccination (Days 1 to 29 and Days 29 to 57)
Intensity of Unsolicited AEs Per the Investigator's Assessment Occurring on the Day of Vaccination and the Following 28 Days After Any Dose
Diaries were used for collection of unsolicited AEs on each vaccination day and the following 28 days. In addition, participants were contacted by phone to verify whether they had any health concerns since the last visit. Participants were included only once, at the maximum severity. 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: Up to 28 days after vaccination (Days 1 to 29 and Days 29 to 57)
Number of Participants Who Experienced a Serious Adverse Event (SAE) During the Trial
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 each occurrence of each AE.
Time frame: Up to Day 57
Number of Participants Who Experienced an Adverse Event of Special Interest (AESI) During the Trial
AESIs included: * AEs with a suspected immune-mediated etiology including potential immune-mediated diseases. * Other AEs relevant to SARS-CoV-2 vaccine development or the target disease. * Non-serious intercurrent medical conditions that may affect the immune response to vaccination was collected throughout the trial. Participants who received a licensed/authorized vaccine were censored at the day after receiving the licensed/authorized vaccine. The Investigator assessed the relationship between trial vaccine and each occurrence of each AE.
Time frame: Up to Day 57
Number of Participants Seroconverting for SARS-CoV-2 Spike Protein Receptor-Binding Domain (RBD) Antibodies on Day 43
Seroconversion was defined as any increase in titer in antibodies against SARS-CoV-2 RBD versus baseline. Participants who received a licensed/authorized vaccine were censored at the day after receiving the licensed/ authorized vaccine.
Time frame: Baseline and Day 43
Geometric Mean Titers (GMTs) of Serum SARS-CoV-2 Spike Protein RBD Antibodies on Day 43
The SARS-CoV-2 spike RBD protein-specific antibodies are expressed as GMT (geometric mean of reciprocal duplicate dilutions). Concentration/titers marked as below the lower limit of quantification (LLOQ) were arbitrary replaced by half of the LLOQ for GMT computations purpose. Participants who received a licensed/authorized vaccine were censored at the day after receiving the licensed/authorized vaccine.
Time frame: Day 43
Subset Participants: Number of Participants Seroconverting for SARS-CoV-2 Neutralizing Antibodies on Day 43
Seroconversion was defined as any increase in titer of SARS-CoV-2 neutralizing antibodies versus baseline. Participants who received a licensed/authorized vaccine were censored at the day after receiving the licensed/authorized vaccine.
Time frame: Baseline and Day 43
Subset Participants: GMTs of Serum SARS-CoV-2 Neutralizing Antibodies on Day 43
The SARS-CoV-2 neutralizing antibodies are expressed as GMT (geometric mean of reciprocal duplicate dilutions). Concentrations/titers marked as below the LLOQ were arbitrary replaced by half of the LLOQ for GMT computations purpose. Participants who received a licensed/authorized vaccine were censored at the day after receiving the licensed/authorized vaccine.
Time frame: Day 43
Number of Participants Seroconverting for SARS-CoV-2 Spike Protein RBD Antibodies on Days 29, 120, 211 and 393
Seroconversion was defined as any increase in titer in antibodies against SARS-CoV-2 RBD versus baseline. Participants who received a licensed/authorized vaccine were censored at the day after receiving the licensed/ authorized vaccine.
Time frame: Baseline and Days 29, 120, 211 and 393
GMTs of Serum SARS-CoV-2 Spike Protein RBD Antibodies on Days 29, 120, 211 and 393
The SARS-CoV-2 spike RBD protein-specific antibodies are expressed as GMT (geometric mean of reciprocal duplicate dilutions). Concentrations/titers marked as below the LLOQ were arbitrary replaced by half of the LLOQ for GMT computations purpose. Participants who received a licensed/authorized vaccine were censored at the day after receiving the licensed/authorized vaccine.
Time frame: Days 29, 120, 211 and 393
Subset Participants: Number of Participants Seroconverting for SARS-CoV-2 Neutralizing Antibodies on Days 29 and 120
Seroconversion was defined as any increase in titer of SARS-CoV-2 neutralizing antibodies versus baseline. Participants who received a licensed/authorized vaccine were censored at the day after receiving the licensed/authorized vaccine.
Time frame: Baseline and Days 29 and 120
Subset Participants: GMTs of Serum SARS-CoV-2 Neutralizing Antibodies on Days 29 and 120
The SARS-CoV-2 neutralizing antibodies are expressed as GMT (geometric mean of reciprocal duplicate dilutions). Concentrations/titers marked as below the LLOQ were arbitrary replaced by half of the LLOQ for GMT computations purpose. Participants who received a licensed/authorized vaccine were censored at the day after receiving the licensed/authorized vaccine.
Time frame: Days 29 and 120