A Study to Evaluate the Safety and Immunogenicity of Vaccine CVnCoV in Healthy Adults in Germany for COVID-19

Study Overview
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Brief Summary
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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.

Official Title
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COVID-19: A Phase 3, Randomized, Observer-Blinded, Placebo-Controlled Clinical Study Evaluating the Safety and Immunogenicity of Investigational SARS-CoV-2 mRNA Vaccine CVnCoV in Adult Health Care Workers in Mainz (Germany)

Conditions
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Coronavirus, Covid19, SARS-CoV-2, Severe Acute Respiratory Syndrome

Intervention / Treatment
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* Biological: CVnCoV Vaccine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CVnCoV: Group 1, Lot 1<br>Participants in Group 1 will be vaccinated with CVnCoV 12 µg mRNA on Day 1 and Day 29 in the deltoid area, preferably in the non-dominant arm. | Biological: CVnCoV Vaccine<br>* Intramuscular injection<br>* Other names: CV07050101;|
| Experimental: CVnCoV: Group 2, Lot 2<br>Participants in Group 2 will be vaccinated with CVnCoV 12 µg mRNA on Day 1 and Day 29 in the deltoid area, preferably in the non-dominant arm. | Biological: CVnCoV Vaccine<br>* Intramuscular injection<br>* Other names: CV07050101;|
| Placebo Comparator: Placebo<br>Participants will receive a placebo on Day 1 and Day 29 in the deltoid area, preferably in the non-dominant arm. | Drug: Placebo<br>* Intramuscular injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to 6 months after Dose 2 (Days 29 to 211) | 
| 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. | Day 1 to Day 393 | 
| 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. | Day 1 to Day 393 | 
| 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. | Up to 1 year after Dose 2 (Days 29 to 393) | 
| 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. | Day 1 to Day 393 | 
| 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 | 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. | Day 1 to 28 days after Dose 2 (Day 57) | 
| 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. | Day 1 to 28 days after Dose 2 (Day 57) | 
| 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. | Baseline (Day 1), Day 29 and Day 43 | 
| 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. | Day 1, Day 29 and Day 43 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline (Day 1), Day 29 and Day 43 | 
| 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. | Day 1, Day 29 and Day 43 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vaccine, SARS, COVID, Safety, Immunogenicity