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

Study Overview
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Brief Summary
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This study aims to evaluate the safety and reactogenicity profile after 1 and 2 dose administrations of CVnCoV at different dose levels.

Detailed Description
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Funded by Coalition for Epidemic Preparedness Innovations (CEPI). 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.).

Official Title
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COVID-19: A Phase 1, Partially Blind, Placebo-controlled, Dose Escalation, First-in-human, Clinical Trial to Evaluate the Safety, Reactogenicity and Immunogenicity After 1 and 2 Doses of the Investigational SARS-CoV-2 mRNA Vaccine CVnCoV Administered Intramuscularly in Healthy Adults

Conditions
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Severe Acute Respiratory Syndrome, Coronavirus, SARS-CoV-2, COVID-19

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 for all participants: Healthy male and female participants aged 18 to 60 years inclusive. Healthy participant is defined as an individual who is in good general health, not having any mental or physical disorder requiring regular or frequent medication. Expected to be compliant with protocol procedures and available for clinical follow-up through the last planned visit. Physical examination and laboratory results without clinically significant findings according to the Investigator's assessment. Body Mass Index (BMI) ≥18.0 and ≤30.0kg/m^2 (≥18.0 and ≤32.0kg/m2 for participants with SARS-CoV-2 positive serology). Females: At the time of enrollment, negative human chorionic gonadotropin (hCG) pregnancy test (serum) for women presumed to be of childbearing potential on the day of enrollment. On Day 1 (pre-vaccination): negative urine pregnancy test (hCG), (only required if the serum pregnancy test was performed more than 3 days before). Females of childbearing potential must use highly effective methods of birth control from 1 month 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 occlusion; Vasectomized partner; Sexual abstinence (periodic abstinence [e.g., calendar, ovulation, symptothermal and post-ovulation methods] and withdrawal are not acceptable). Exclusion Criteria: The following criterion applies to all open-label sentinel participants: Participants with SARS-CoV-2 positive serology as confirmed by testing at enrollment. The following criteria apply to all participants, except those with SARS-CoV-2 positive serology: Participants considered at the Investigator's discretion to be at increased risk to acquire COVID-19 disease (including, but not limited to, health care workers with direct involvement in patient care or care of long-term care recipients). History of confirmed COVID-19 disease or known exposure to an individual with confirmed COVID-19 disease or SARS-CoV-2 infection within the past 2 weeks. The following criteria apply to all participants: Use of any investigational or non-registered product (vaccine or drug) other than the trial vaccine within 28 days preceding the administration of the trial vaccine, or planned use during the trial period. Receipt of any other vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrollment in this trial or planned receipt of any vaccine within 28 days of trial vaccine administration. Receipt of any investigational SARS-CoV-2 or other CoV vaccine prior to the administration of the trial vaccine. Any treatment with immunosuppressants or other immune-modifying drugs within 6 months prior to the administration of the trial vaccine or planned use during the trial, with the exception of topically-applied steroids. Corticosteroids used in the context of COVID-19 disease of participants with SARS CoV 2 positive serology are not exclusionary. Any medically diagnosed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination, including known human immunodeficiency virus infection, hepatitis B virus infection and hepatitis C virus infection. History of a pIMD (potential immune-mediated disease). History of angioedema. Any known allergy, including allergy to any component of CVnCoV or aminoglycoside antibiotics. A history of hay fever or seasonal allergies (pollinosis) that does not require current treatment (e.g., anti-histamines) during the vaccination period (1 month before first vaccination until 1 month after last vaccination) is not exclusionary. History of or current alcohol and/or drug abuse. Participants who are active smokers, were active smokers within the last year (including any vaping in the last year) or have a total smoking history ≥10 pack years. Active or currently active SARS-CoV-2 infection as confirmed by reactive PCR within 3 days of first trial vaccine administration. History of confirmed SARS or MERS Administration of immunoglobulins (Igs) and/or any blood products within the 3 months preceding the administration of any dose of the trial vaccine. Presence or evidence of significant acute or chronic, medical or psychiatric illness. Significant medical or psychiatric illnesses include but are not limited to: Respiratory disease (e.g., chronic obstructive pulmonary disease [COPD], asthma) requiring daily medications currently or any treatment of respiratory disease exacerbations (e.g., asthma exacerbation) in the last 5 years. Respiratory disease with clinically significant dyspnea in the last 5 years (except COVID-19 disease in participants with SARS-CoV-2 positive serology). Asthma medications: inhaled, oral, or intravenous (IV) corticosteroids, leukotriene modifiers, long- and short-acting beta agonists, theophylline, ipratropium, biologics. Significant cardiovascular disease (e.g., congestive heart failure, cardiomyopathy, ischemic heart disease, history of stroke, peripheral artery disease, pulmonary embolism) or history of myocarditis or pericarditis as an adult. Elevated blood pressure or hypertension, even if well-controlled. Diabetes mellitus type 1 or 2. History of any neurological disorders or seizures including Guillain-Barré syndrome, with the exception of febrile seizures during childhood. Current or past malignancy, unless completely resolved without sequelae for >5 years. Foreseeable non-compliance with protocol as judged by the Investigator. For females: pregnancy or lactation. History of any anaphylactic reactions. Participants with impaired coagulation or any bleeding disorder in whom an IM injection or a blood draw is contraindicated. Participants employed by the Sponsor, Investigator or trial site, or relatives of research staff working on this trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Sequential Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation CVnCoV<br>Participants will be vaccinated with CVnCoV at escalating dose levels on Day 1 and Day 29. Safety data will inform the decision to continue enrolling at the current dose level, or to proceed to dose escalation. Initially, dose levels of 2, 4 and 8 μg will be evaluated. Dose levels of 2, 4, 6, 8 and 12µg will be evaluated with potential increase to dose levels up to 20 μg. | Biological: CVnCoV Vaccine<br>* Participants will receive an intramuscular injection by needle in the deltoid area.<br>* Other names: CV07050101;|
| Placebo Comparator: Dose Escalation Placebo<br>Participants will be given placebo on Day 1 and Day 29. | Drug: Placebo<br>* Participants will receive an intramuscular injection by needle in the deltoid area.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Grade 3 Adverse Reactions or Any Serious Adverse Event (SAE) Considered Related to Trial Vaccine Within at Least 24 Hours After the First Vaccination | Grade 3 refers to the highest grading on the FDA toxicity scale where a higher grade indicates a worse outcome. 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. | Up to 24 hours after vaccination on Day 1 | 
| Number of Participants With Grade 3 Adverse Reactions or Any Serious Adverse Event (SAE) Considered Related to Trial Vaccine Within at Least 60 Hours After the First Vaccination | Grade 3 refers to the highest grading on the FDA toxicity scale where a higher grade indicates a worse outcome. 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. | Up to 60 hours after vaccination on Day 1 | 
| Number of Participants With Solicited Local Adverse Events | Reactogenicity was assessed daily via collection of solicited local AEs (injection site pain, redness, swelling, and itching) using paper diary cards. | Up to 7 days after vaccination (Days 1 to 8 and Day 29 to 36) | 
| Intensity of Solicited Local Adverse Events Per the FDA Toxicity Grading Scale | Reactogenicity was assessed daily via collection of solicited local AEs (injection site pain, redness, swelling, and itching) 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. | Up to 7 days after vaccination (Days 1 to 8 and Days 29 to 36) | 
| Duration of Solicited Local Adverse Events | Reactogenicity was assessed daily via collection of solicited local AEs (injection site pain, redness, swelling, and itching) using paper diary cards. Duration was calculated as consecutive days with a respective solicited AE regardless of the grade of the AE. | Up to 7 days after vaccination (Days 1 to 8 and Days 29 to 36) | 
| Number of Participants With Solicited Systemic Adverse Events | Reactogenicity was assessed daily via collection of solicited systemic AEs (fever, headache, fatigue, chills, myalgia, arthralgia, nausea/vomiting, and diarrhea) using paper diary cards. | Up to 7 days after vaccination (Days 1 to 8 and Days 29 to 36) | 
| Intensity of Solicited Systemic Adverse Events Per the FDA Toxicity Grading Scale | Reactogenicity was assessed daily via collection of 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. | Up to 7 days after vaccination (Days 1 to 8 and Days 29 to 36) | 
| Duration of Solicited Systemic Adverse Events | Reactogenicity was assessed daily via collection of 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. | Up to 7 days after vaccination (Days 1 to 8 and Days 29 to 36) | 
| Number of Participants With Solicited Systemic Adverse Events Considered Related to Trial Vaccine | Reactogenicity was assessed daily via collection of solicited systemic AEs (fever, headache, fatigue, chills, myalgia, arthralgia, nausea/vomiting, and diarrhea) using paper diary cards. The Investigator assessed the relationship between trial vaccine and each occurrence of each AE. | Up to 7 days after vaccination (Days 1 to 8 and Days 29 to 36) | 
| Number of Participants With Unsolicited Adverse Events | 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. | Up to 28 days after vaccination (Days 1 to 29 and Days 29 to 57) | 
| Intensity of Unsolicited Adverse Events Assessed by the Investigator | 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. | Up to 28 days after vaccination (Days 1 to 29 and Days 29 to 57) | 
| Number of Participants With Unsolicited Adverse Events Considered Related to Trial Vaccine | 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. | Up to 28 days after vaccination (Days 1 to 29 and Days 29 to 57) | 
| Number of Participants With One or More Serious Adverse Events (SAEs) | 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. | Baseline to Day 393 | 
| Number of Participants With One or More Serious Adverse Events (SAEs) Considered Related to Trial Vaccine | 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. | Baseline to Day 393 | 
| Number of Participants With One or More Adverse Events of Special Interest (AESIs) | The following events will be considered as AESIs: adverse events with a suspected immune-mediated etiology, COVID-19 disease and other adverse events relevant to SARS-CoV vaccine development or the target disease. | Day 1 to Day 393 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Seroconverting for SARS-CoV-2 Spike Protein Antibodies | Measured using Enzyme-Linked Immunosorbent Assay (ELISA). In participants who did not get exposed to SARS-CoV-2 before the trial or during the trial before the applicable sample was collected, as measured by ELISA to SARS-CoV-2 N-antigen, seroconversion is defined as an increase in titer in antibodies against SARS-CoV-2 spike protein versus baseline. In subjects seropositive for SARS-CoV-2 at baseline, seroconversion is defined as a 2-fold increase in titer in antibodies against SARS-CoV-2 spike protein versus baseline. | Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 120 and Day 211 | 
| Geometric Mean Titers (GMTs) of Serum SARS-CoV-2 Spike Protein Antibodies | Measured using Enzyme-Linked Immunosorbent Assay (ELISA). | Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 120 and Day 211 | 
| Number of Participants Seroconverting for SARS-CoV-2 Spike Protein Receptor-Binding Domain (RBD) Antibodies | Measured using Enzyme-Linked Immunosorbent Assay (ELISA). In participants who did not get exposed to SARS-CoV-2 before the trial or during the trial before the applicable sample was collected, as measured by ELISA to SARS-CoV-2 N-antigen, seroconversion is defined as an increase in titer in antibodies against SARS-CoV-2 spike RBD protein versus baseline. In subjects seropositive for SARS-CoV-2 at baseline, seroconversion is defined as a 2-fold increase in titer in antibodies against SARS-CoV-2 spike RBD protein versus baseline. | Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 120 and Day 211 | 
| Geometric Mean Titers (GMTs) of Serum SARS-CoV-2 Spike Protein Receptor-Binding Domain (RBD) Antibodies | Measured using Enzyme-Linked Immunosorbent Assay (ELISA). | Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 120 and Day 211 | 
| Number of Participants Seroconverting for SARS-CoV-2 Neutralizing Antibodies | Measured using an activity assay. In participants who did not get exposed to SARS-CoV-2 before the trial or during the trial before the applicable sample was collected, as measured by ELISA to SARS-CoV-2 N-antigen, seroconversion is defined as an increase in titer in SARS-CoV-2 neutralizing antibodies versus baseline. In participants seropositive for SARS-CoV-2 at baseline, seroconversion is defined as a 2-fold increase in titer in SARS-CoV-2 neutralizing antibodies versus baseline. | Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 120 and Day 211 | 
| Geometric Mean Titers (GMTs) of Serum SARS-CoV-2 Neutralizing Antibodies | Measured using an activity assay. | Day 8, Day 15, Day 29, Day 36, Day 43, Day 57, Day 120 and Day 211 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, Reactogenicity, Immunogenicity, Vaccine, CEPI