Safety and Immunogenicity Study of a Booster Dose of the Investigational CV0501 mRNA COVID-19 Vaccine in Adults at Least 18 Years Old

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 and Immunogenicity Study of a Booster Dose of the Investigational CV0501 mRNA COVID-19 Vaccine in Adults at Least 18 Years Old

Conditions
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SARS-CoV-2

Intervention / Treatment
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* Biological: CV0501 (3 μg)
* Biological: CV0501 (6 μg)
* Biological: CV0501 (12 μg)
* Biological: CV0501 (25 μg)
* Biological: CV0501 (50 μg)
* Biological: CV0501 (75 μg)
* Biological: CV0501 (100 μg)
* Biological: CV0501 (150 μg)
* Biological: CV0501 (200 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 Has received at least 2 doses of Comirnaty or Moderna COVID-19 Vaccine (Spikevax®), with the last dose of vaccine received at least 6 months prior to screening Negative for SARS-CoV-2 infection by RT-PCR test at screening Is a male or nonpregnant female ≥18 years old If the participant is a woman of child bearing potential, the participant agrees to use at least 1 highly effective form of contraception for at least 30 days prior to the study vaccination up to 3 months after study vaccination. Agrees to refrain from blood or plasma donation from the first study vaccination through end of study. Has a body mass index of 18 to 40 kg/m2, inclusive, at screening. Is healthy or medically stable as determined by investigator judgment based on medical history, clinical laboratory tests, vital sign measurements, and physical examination findings Exclusion Criteria: Participant is female and has a positive pregnancy test result at screening. Participant is female and is breastfeeding or will (re)start breastfeeding from the study vaccination to 3 months after vaccination. Has an acute febrile illness with temperature ≥38.0°C or ≥100.4°F within 72 hours before study vaccination. Individuals with suspected COVID-19 symptoms should be excluded and referred for medical care. Has a history of documented SARS-CoV-2 infection or COVID-19 within 6 months before screening. Has a documented medical history of HIV, hepatitis B or hepatitis C infection prior to screening, or a positive test for these conditions at screening. Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease (eg, malignancy) or immunosuppressive/cytotoxic therapy (eg, medications used during cancer chemotherapy, organ transplantation or to treat autoimmune disorders). 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 immunotherapy injections, immunoglobulin, interferon, immunomodulators, cytotoxic drugs, or other similar or toxic drugs within 6 months of the first study vaccination. Inclusion of persons who use low dose topical, ophthalmic, inhaled, or intranasal steroid preparations is permitted. 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 a new onset, clinically significant, abnormal biochemistry or hematology finding (defined as ≥Grade 1) at screening (adults with Grade 1 laboratory abnormalities that have been stable for at least 6 months before enrollment may be included in the study). Individuals with a history of autoimmune disease or an active autoimmune disease requiring therapeutic intervention, including but not limited to: systemic or cutaneous lupus erythematosus, autoimmune arthritis/rheumatoid arthritis, Guillain- Barré syndrome, multiple sclerosis, Sjögren's syndrome, idiopathic thrombocytopenia purpura, glomerulonephritis, autoimmune thyroiditis, giant cell arteritis (temporal arteritis), Takayasu arteritis, granulomatosis with polyangiitis, psoriasis, and insulin-dependent diabetes mellitus (Type 1). Has an unstable chronic medical condition. This refers to a condition requiring a new medication or increase in dose of current medication(s) or a condition requiring hospitalization within 6 months prior to screening. Has a history of hypersensitivity or severe allergic reaction, including anaphylaxis, generalized urticaria, angioedema, and other significant reactions, to vaccines or to any component of the investigational product. Has received or plans to receive any licensed vaccine, within 4 weeks before or 4 weeks 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. Has had known close contact with anyone who had a confirmed SARS-CoV-2 infection within 2 weeks before study vaccination. Rescreening of these participants permitted after quarantine period is complete. Has participated or plans to participate in another investigational study involving any investigational product or device within 6 months or 5 half-lives, whichever is longer, before the study vaccination through end of study. Has received or plans to receive immunoglobulins or any blood or blood products within 3 months before the first study vaccination through end of study. Has a bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindicate intramuscular injection. 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 (eg, tattoo) that would interfere with the ability to observe local reactions at the injection site. Has a medical disease or psychiatric condition that, in the opinion of the investigator, precludes study participation because it would place the individual at an unacceptable risk of injury, render the individual unable to meet the requirements of the protocol, or interfere with the individual's successful completion of the trial. Participant is an employee or family member of the investigator or study site personnel.

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: CV0501 Dose Cohort 1 (12 μg)<br>Enrollment will be staggered, beginning with Group 1a (12 μg, younger adults). Initiation of enrollment in Group 1b (12 μg, older adults) will depend on Safety Review Team (SRT) review of safety data up to Day 8 from a minimum of 10 participants in Group 1a. | Biological: CV0501 (12 μg)<br>* Study vaccine will be administered as a single intramuscular injection in the deltoid area, preferably in the nondominant arm.<br>|
| Experimental: Part A: CV0501 Dose Cohort 2 (25 μg)<br>For both Group 2a (younger) and Group 2b (older age), initiation of enrollment in the subsequent group at the next dose level for Cohorts 2-5 will depend on SRT review of safety data up to Day 8 from a minimum of 10 participants, from the previous dose level in the same age group. | Biological: CV0501 (25 μg)<br>* Study vaccine will be administered as a single intramuscular injection in the deltoid area, preferably in the nondominant arm.<br>|
| Experimental: Part A: CV0501 Dose Cohort 3 (50 μg)<br>For both Group 3a (younger) and Group 3b (older age), initiation of enrollment in the subsequent group at the next dose level for Cohorts 2-5 will depend on SRT review of safety data up to Day 8 from a minimum of 10 participants, from the previous dose level in the same age group. | Biological: CV0501 (50 μg)<br>* Study vaccine will be administered as a single intramuscular injection in the deltoid area, preferably in the nondominant arm.<br>|
| Experimental: Part A: CV0501 Dose Cohort 4 (75 μg or 100 μg)<br>For each of the groups in Cohort 4, Group 4a (younger) and Group 4b (older age),the SRT may recommend a dose specified by the dosing scenarios in the protocol, based on their review of all available safety data. The SRT will use the same approach, independently, to select the dose levels for older participants (Group 4b) and younger participants (Group 4a). | Biological: CV0501 (75 μg)<br>* Study vaccine will be administered as a single intramuscular injection in the deltoid area, preferably in the nondominant arm.<br>Biological: CV0501 (100 μg)<br>* Study vaccine will be administered as a single intramuscular injection in the deltoid area, preferably in the nondominant arm.<br>|
| Experimental: Part A: CV0501 Dose Cohort 5 (100 μg, 150 μg or 200 μg)<br>For each of the groups in Cohort 5, Group 5a (younger) and Group 5b (older age), the SRT may recommend a dose specified by the dosing scenarios in the protocol, based on their review of all available safety data. The SRT will use the same approach, independently, to select the dose levels for older participants (Group 5b) and younger participants (Group 5a). | Biological: CV0501 (100 μg)<br>* Study vaccine will be administered as a single intramuscular injection in the deltoid area, preferably in the nondominant arm.<br>Biological: CV0501 (150 μg)<br>* Study vaccine will be administered as a single intramuscular injection in the deltoid area, preferably in the nondominant arm.<br>Biological: CV0501 (200 μg)<br>* Study vaccine will be administered as a single intramuscular injection in the deltoid area, preferably in the nondominant arm.<br>|
| Experimental: Part B: CV0501 Dose Cohort 6 (3 μg)<br>Part B, designed to comprise 2 single age group cohorts, Group 6a (≥18 to <65 years old) will start based on the first interim analysis of safety and immunogenicity data, provided that the SRT assesses the 12 μg dose to be immunogenic and safe. | Biological: CV0501 (6 μg)<br>* Study vaccine will be administered as a single intramuscular injection in the deltoid area, preferably in the nondominant arm.<br>|
| Experimental: Part B: CV0501 Dose Cohort 7 (6 μg)<br>Part B, designed to comprise 2 single age group cohorts, Group 7a (≥18 to <65 years old) will start based on the first interim analysis of safety and immunogenicity data, provided that the SRT assesses the 12 μg dose to be immunogenic and safe. | Biological: CV0501 (3 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 solicited local adverse events (AE) during 7 days after vaccination |  | Days 1 through 7 | 
| Percentage of participants with solicited systemic AE during 7 days after vaccination |  | Days 1 through 7 | 
| Percentage of participants with each abnormal clinical safety laboratory finding for 8 days after study vaccination |  | 8 days from vaccination at Day 1 | 
| Percentage of participants with unsolicited AEs for 28 days after study vaccination |  | 28 days from vaccination at Day 1 | 
| 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 from vaccination at Day 1 | 
| 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 serious adverse event (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 from vaccination at Day 1 | 
| 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 from vaccination at Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers (GMTs) of neutralizing Ab against pseudovirus bearing S protein from SARS-CoV-2 WT, Omicron, and Delta variants at each collection timepoint |  | Days 1, 8, 15, 29, 91, and 181 | 
| Geometric Mean Increase (GMI) from baseline of neutralizing Ab titers against pseudovirus bearing S protein from SARS-CoV-2 WT, Omicron, and Delta variants at each collection time point |  | Days 1, 8, 15, 29, 91, and 181 | 
| Seroresponse rate 28 days after the booster dose, based on neutralizing Ab titers against pseudoviruses bearing S protein from SARS-CoV-2 WT, Omicron, and Delta variants at each collection timepoint | Seroresponse is defined as postboost titers ≥ 4× preboost titers | At day 29 | 

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