Safety, Reactogenicity, and Immunogenicity Trial of CV2CoV mRNA Vaccine Against SARS-CoV-2 in Seropositive Adult Participants

Study Overview
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Brief Summary
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Prevention of COVID-19 caused by SARS-CoV-2.

Official Title
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A Phase 1, Open-label, Safety, Reactogenicity, and Immunogenicity Trial of the CV2CoV mRNA Vaccine Against SARS CoV 2 in Seropositive Adult Participants

Conditions
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SARS-CoV-2

Intervention / Treatment
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* Biological: CV2CoV (2 µg)
* Biological: CV2CoV (4 µg)
* Biological: CV2CoV (8 µg)
* Biological: CV2CoV (12 µg)
* Biological: CV2CoV (16 µg)
* Biological: CV2CoV (20 µg)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must provide documented informed consent prior to any study procedures being performed. Is capable of understanding and agrees to comply with planned study procedures and to be available for all study visits, including being willing and able to use electronic devices during the study. Has received at least 2 doses of Pfizer-BioNTech (Comirnaty) or Moderna (Spikevax) mRNA COVID-19 vaccine with the last dose of vaccine received at least 6 months prior to Screening and has provided documentation of receiving the vaccination series. Negative for SARS-CoV-2 infection by RT-PCR test at Screening. Is a male or nonpregnant female 18 to <65 years of age (younger adult group) or ≥65 years of age (older adult group) at Screening. Has a body mass index of 18 to 34.9 kg/m^2, inclusive, at Screening. If the participant is a woman of child bearing potential the participant agrees to practice true abstinence or use at least 1 highly effective form of contraception for at least 30 days prior to study vaccination up to 3 months after study vaccination. Agrees to refrain from blood or plasma donation from Screening and throughout the end of the study. Is healthy or medically stable as determined by medical history, clinical laboratory tests, vital sign measurements, and physical examination findings, as determined by investigator judgment. Exclusion Criteria: Participant is female and has a positive serum pregnancy test result at Screening or plans to become pregnant during the study. Participant is female and is breastfeeding or plans to breastfeed from study vaccination to 3 months after study vaccination. Has any clinically significant abnormal biochemistry or hematology finding (defined as ≥Grade 1) at Screening. Has any medical disease or condition that, in the opinion of the investigator, precludes study participation. This includes any acute, subacute, intermittent, or chronic medical disease or condition that would place the participant at an unacceptable risk of injury, render the participant unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the participant's successful completion of the trial. Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease or immunosuppressive/cytotoxic therapy. History of myocarditis, pericarditis, or idiopathic cardiomyopathy, or presence of any medical condition that increases risk of myocarditis or pericarditis, including cocaine abuse, cardiomyopathy, endomyocardial fibrosis, hypereosinophilic syndrome, hypersensitivity myocarditis, eosinophilic granulomatosis with polyangiitis, persistent myocardial viral infection (eg, due to enterovirus or adenovirus), and celiac disease. Has an acute febrile illness with a temperature ≥38.0°C or ≥100.4°F observed by the participant or at the study site within 72 hours prior to study vaccination. Participants with suspected COVID-19 symptoms should be excluded and referred for medical care. Has a prior confirmed diagnosis of chronic hepatitis B, hepatitis C, or HIV 1/2 infection or evidence of active infection at Screening. Has participated or plans to participate in another investigational study involving any investigational drug or device within 60 days or 5 half-lives, whichever is longer, before study vaccination and throughout the end of the study. Has previously participated in an investigational vaccine study with investigational vaccine administered within 6 months of study vaccination OR has received the last dose of >1 COVID-19 vaccine series (investigational and/or authorized) in the last 12 months. Has received or plans to receive any licensed vaccine within 4 weeks before or after study vaccination. Inactivated vaccines for influenza are permitted during the study if they are administered at least 14 days before or after study vaccination. Is planning to receive a COVID-19 booster vaccination for the duration of the study (for adults who are not covered by local recommendations to receive booster per current standard of care) or is planning to receive a COVID-19 booster vaccination on or before Day 29 of the study (for adults covered by local recommendations to receive booster). Has received or plans to receive immunoglobulins or any blood or blood products within 90 days before study vaccination and throughout the study. Has a history of hypersensitivity or severe allergic reaction, including anaphylaxis, generalized urticaria, angioedema, and other significant reactions to any previous vaccine or any component of the IP. Has a history of hypersensitivity or severe allergic reaction (including anaphylaxis, generalized urticaria, angioedema, and other significant reactions) to beta lactam antibiotics. Reports chronic use (more than 14 continuous days) of any medication that may be associated with changes in immune function including, but not limited to, systemic corticosteroids exceeding 10 mg/day of prednisone equivalent, allergy injections, immunoglobulins, interferons, immunomodulators, cytotoxic drugs, or other similar or toxic drugs within 6 months of study vaccination. Has a bleeding disorder or prior history of significant bleeding or bruising after IM injections or venipuncture. Has a history of alcohol abuse or other recreational drug use (excluding cannabis) within 6 months before study vaccination. Has any abnormal skin condition or permanent body art that would interfere with the ability to observe local reactions at the study vaccination injection site. Has had known close contact with anyone who had a confirmed SARS-CoV-2 infection within 14 days before study vaccination. Participant is an employee or family member of the investigator or study site personnel. Has any self-reported or medically-documented significant medical or psychiatric condition. Significant medical conditions include, but are not limited to, the following: Moderate or severe respiratory disease Uncontrolled hypertension, defined as an average systolic blood pressure ≥140 mmHg for participants ≤60 years old, and ≥150 mmHg for participants >60 years old, or a diastolic blood pressure ≥90 mmHg for any age Significant cardiovascular disease or history of myocarditis or pericarditis Neurological or neurodevelopmental conditions Ongoing malignancy or recent diagnosis of malignancy in the last 5 years (excluding basal cell and squamous cell carcinoma of the skin) Tuberculosis or nontuberculosis mycobacterial infection Autoimmune disease, including hypothyroidism without a defined nonautoimmune cause Immunodeficiency of any cause, including from solid organ transplant, blood or bone marrow transplant, use of corticosteroids, or use of other immune weakening medicines Type 1 or 2 diabetes mellitus regardless of disease control Has any of the following self-reported or medically-documented risk factors for severe COVID-19: Cancer Chronic kidney disease Sickle cell disease Cerebrovascular disease Cystic fibrosis Chronic liver disease Pulmonary fibrosis Thalassemia Smoking or other inhaled substance use, including tobacco, cannabis, or nicotine vapors, with an average of ≥5 cigarettes a day or equivalent (currently or within 1 year of Screening). Has a history of documented SARS-CoV-2 infection or COVID-19 within 6 months before Screening.

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: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: The study will be conducted in 5 sequential cohorts with dose escalation. Each cohort will include 2 age groups.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CV2CoV Dose Cohort 1 (2µg or 4µg)<br>Group 1a will receive CV2CoV dose level 2 µg Group 1b will receive CV2CoV dose level 4 µg | Biological: CV2CoV (2 µg)<br>* Study vaccine will be administered as a single intramuscular injection in the deltoid area, preferably in the nondominant arm.<br>Biological: CV2CoV (4 µg)<br>* Study vaccine will be administered as a single intramuscular injection in the deltoid area, preferably in the nondominant arm.<br>|
| Experimental: CV2CoV Dose Cohort 2 (8 µg)<br>Cohort 2 will receive CV2CoV dose level 8 µg Enrollment into Cohort 2 will begin after the Safety Review Team (SRT) has reviewed safety data from 2 sentinel participants from the previous dose cohort. | Biological: CV2CoV (8 µg)<br>* Study vaccine will be administered as a single intramuscular injection in the deltoid area, preferably in the nondominant arm.<br>|
| Experimental: CV2CoV Dose Cohort 3 (12 µg)<br>Cohort 3 will receive CV2CoV dose level 12 µg Enrollment into Cohort 3 will begin after the SRT has reviewed safety data from 2 sentinel participants from the previous dose cohort. | Biological: CV2CoV (12 µg)<br>* Study vaccine will be administered as a single intramuscular injection in the deltoid area, preferably in the nondominant arm.<br>|
| Experimental: CV2CoV Dose Cohort 4 (16 µg)<br>Cohort 4 will receive CV2CoV dose level 16 µg Enrollment into Cohort 4 will begin after the SRT has reviewed safety data from all participants in the previous dose cohort. | Biological: CV2CoV (16 µg)<br>* Study vaccine will be administered as a single intramuscular injection in the deltoid area, preferably in the nondominant arm.<br>|
| Experimental: CV2CoV Dose Cohort 5 (20 µg)<br>Cohort 5 will receive CV2CoV dose level 20 µg Enrollment into Cohort 5 will begin after the SRT has reviewed safety data from all participants in the previous dose cohort. | Biological: CV2CoV (20 µg)<br>* Study vaccine will be administered as a single intramuscular injection in the deltoid area, preferably in the nondominant arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with adverse events of special interest (AESIs) from study vaccination through the end of the study | An AESI (serious or nonserious) is defined as an AE or SAE of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor could be appropriate. | 180 days after the study vaccine administration | 
| Percentage of participants with serious adverse events (SAEs) from study vaccination through the end of the study | An SAE is defined as any event that: Results in death Is immediately life-threatening Requires inpatient hospitalization or prolongation of existing hospitalization Results in persistent or significant disability/incapacity Is a congenital anomaly/birth defect Is a spontaneous miscarriage Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered SAEs when, based upon appropriate medical judgment, they may jeopardize the participant or may require medical or surgical intervention to prevent one of the outcomes listed in this definition. Examples of such medical events include allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias or convulsions that do not result in inpatient hospitalization, or the development of drug dependency or drug abuse. | 180 days after the study vaccine administration | 
| Percentage of participants with medically attended adverse events (MAAEs) from study vaccination through the end of the study | An MAAE is defined as an AE that results in a visit to a medical professional. Medically attended visits are defined as a telemedicine visit, physician's office visit, urgent care visit, emergency room visit, hospitalization, or death. | 180 days after the study vaccine administration | 
| Percentage of participants with solicited local adverse events (AEs) up to 7 days after study vaccination | Local solicited AEs will include injection site pain, redness, swelling, and lymphadenopathy. | Days 1 to 7 | 
| Percentage of participants with each solicited systemic AEs up to 7 days after study vaccination | Systemic solicited events will include fever, headache, fatigue, myalgia, arthralgia, and chills. | Days 1 to 7 | 
| Percentage of participants with unsolicited AEs up to 28 days after study vaccination, including clinically relevant abnormal clinical safety laboratory findings | An unsolicited AE is defined as any AE that is volunteered from the participant and occurs within 28 days after vaccination. | 28 days after the study vaccine administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers (GMTs) of neutralizing antibody titers against pseudovirus bearing spike protein from SARS CoV 2 wild type (WT) at each collection time point |  | Days 1, 8, 15, 29, 85, and 180 | 
| Percentage of participants with seroresponse (≥4 fold rise from baseline) at Day 29 after the booster dose |  | 29 days post booster dose | 
| Geometric Mean Increase (GMI) from baseline of neutralizing antibody titers against pseudovirus bearing spike protein from SARS CoV 2 WT at each collection time point |  | Days 8, 15, 29, 85, and 180 | 
| GMTs of binding Immunoglobulin G (IgG) against SARS CoV-2 S protein and Receptor-Binding Domain (RBD) at each collection time point. |  | Days 8, 15, 29, 85, 180 | 
| GMI from baseline of binding IgG against SARS CoV-2 S protein and RBD at each collection time point |  | Day 8, 15, 29, 85, 180 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Pandemic, Booster vaccination