A Study to Assess the Safety and Immunogenicity of a COVID-19 Vaccine Booster in Healthy Adults

Study Overview
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Brief Summary
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This is an open-label, first-in-human, dose-finding study to evaluate the safety and immunogenicity of a booster vaccination of Prime-2-CoV_Beta in healthy participants who had received the full course of vaccination, including booster vaccination (i.e., having received 3 doses) with the Pfizer/BioNTech-BNT162b2 vaccine (Comirnaty).

Detailed Description
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Eligible participants will undergo baseline assessments and will receive 1 injection of Prime-2-CoV_Beta at Day 1. Participants will be followed up through 6 months post-booster vaccination. Follow-up visits will be performed at Days 4, 8, 15, 29, and Months 3 and 6, to assess the safety, tolerability, and immunogenicity of Prime-2-CoV_Beta. Additional safety and tolerability data will be assessed 1 day and 2 days after booster vaccination (Days 2 and 3) by telephone. A total of 60 participants is planned to be vaccinated in 5 cohorts of 12 participants each. Dose ranging of Prime-2-CoV_Beta will be done by dose escalation with doses ranging from 3x10000 plaque forming units (PFUs) up to 3x10 000 000 PFUs

Official Title
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A Phase Ia, Dose-finding Study to Assess the Safety and Immunogenicity of an Orf Virus-based COVID-19 Vaccine Booster (Prime-2-CoV_Beta) in Healthy Adults

Conditions
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COVID-19

Intervention / Treatment
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* Biological: Prime-2-CoV_Beta


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion criteria Healthy adult men or women aged 18 to 55 years Full course of vaccination, including booster vaccination (i.e., having received 3 doses) with Comirnaty, with the booster dose being administered at least 10 weeks before Day 1 as documented in a respective vaccination certificate Able to understand the participant information and providing written informed consent Body mass index of 18.5 to 30.0 kg/m² and weight > 50 kg at Screening Women of childbearing potential must: have a negative pregnancy test at Screening (blood) and at Day 1 (urine) agree to use, and be able to comply with, highly effective measures of contraception without interruption, from 14 days before Prime-2-CoV_Beta booster vaccination until the end of the study. A highly effective method of contraception or birth control (failure rate less than 1% per year when used consistently and correctly) for this study: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal, injectable), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, sexual abstinence or vasectomized sexual partner. Abstinence is only acceptable as true abstinence when this is in line with the preferred and usual lifestyle of the participant (abstinent on a long-term and persistent basis). The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the participant. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods and withdrawal] are not acceptable methods of contraception.) Postmenopausal (no menses for at least 1 year without alternative medical cause) or surgically sterile women (tubal ligation, hysterectomy or bilateral oophorectomy) may be enrolled. Male participants must agree not to intend to father a child or to donate sperm starting at Screening, throughout the clinical study. Male participants must also abstain from sexual intercourse with a female partner (acceptable only if it is the participant's usual form of birth control/lifestyle choice: abstinent on a long-term and persistent basis). The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the participant or use adequate barrier contraception (male condom) during treatment with the investigational product until the end of the study, and ensure that, if they have a female partner of childbearing potential, the partner uses a highly effective contraceptive method as outlined in inclusion criterion number 5 use condoms during the entire study if they have a pregnant partner, to avoid exposure of the fetus to the investigational product Willing and able to comply with all study procedures based on the investigator's judgment Exclusion Criteria: Previous and concomitant therapy: Receipt of any vaccine (licensed or investigational) from 4 weeks before Prime-2-CoV_Beta booster vaccination or anticipated vaccination during the study until 6 weeks after the Prime-2-CoV_Beta booster vaccination Previous vaccination against COVID-19 with vaccines (licensed or investigational) other than Comirnaty Current or previous treatment with another investigational drug and/or medical device (within 30 days of enrollment or 5 half-lives of that investigational drug) Administration of immunoglobulins or any blood products within 2 months of Prime-2-CoV_Beta booster vaccination Chronic administration of medication associated with impaired immune responsiveness as judged by the investigator (including, but not limited to: immunosuppressive therapy, systemic corticosteroids exceeding 10 mg/day of prednisone equivalent, allergy shots for hypo-sensitization, immunoglobulin, interferon, immunomodulators, cytotoxic drugs, or other similar or toxic drugs) within 2 months before the Prime-2-CoV_Beta booster vaccination (Day 1). Inhaled/nebulized, intra-articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted. Previous and concomitant medical condition: Active SARS-CoV-2 infection, confirmed by a commercially available SARS-CoV-2 rapid antigen test at Day 1, or currently on quarantine Confirmed (by real-time quantitative polymerase chain reaction) SARS-CoV-2 infection after 2nd vaccination with Comirnaty Known history of severe adverse reactions to any vaccine and/or severe allergic reactions to any component of the study vaccine, to any drug, or to any other exposure Known history of angioedema Pregnant or lactating women Any confirmed or suspected immunosuppressive or immunodeficient condition Known history of Guillain-Barré Syndrome Known infection with human immunodeficiency virus, hepatitis C virus or hepatitis B virus Active cancer (malignancy) within 5 years before Day 1 (except for adequately treated non-melanomatous skin carcinoma, at the discretion of the investigator) Moderate or severe illness and/or fever > 38.0 °C within 1 week before Prime-2-CoV_Beta booster vaccination Any clinically significant health problem (medical history and physical examination) or clinically significantly abnormal finding in biochemistry and/or hematology blood tests, urinalysis, or electrocardiogram at Screening according to the investigator's opinion Current or history of cardiovascular disease or structural cardiac disease (including chronic or congenital heart conditions, such as chronic hypertension, coronary heart disease, myocardial infarction and arrhythmias, hypertrophic cardiomyopathy, as well as a history of myocarditis after mRNA vaccinations) History of mRNA vaccination-associated adverse events that were in nature and severity beyond the common AEs expected Current or history of gastrointestinal disease, liver disease, renal disease or endocrine disorders, (including diabetes) and neurological illness (excluding migraine), when judged as clinically significant according to the investigator's opinion Current or history of chronic respiratory diseases, including mild asthma treated by on-demand medication (resolved childhood asthma is allowed) Current or history of alcohol and/or drug abuse within the last 6 months before Day 1 Previous and concomitant clinical study experience Current participation in another study or previous enrollment in this clinical study Other exclusion criteria Investigator or employee of the study group or sponsor with direct involvement in the proposed study or relatives of the research staff with direct involvement in the proposed study Prolonged exposure to sheep or goats (e.g., shepherds, sheep farmer)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Cohorts 1 to 5 will include a safety lead with 1 sentinel participant. If no safety issues occurred within the on-site monitoring period as assessed by the investigator and solicited during telephone visits, the next 2 participants in that dose cohort will be vaccinated. After an 48-hour observation period and assuming no safety issues were identified in these 2 participants, an additional 4 participants will be vaccinated. After a 48-hour observation period, and assuming that no safety problems were noted in these 4 participants, the remaining participants in the dosing group will be vaccinated. Each participant will be observed for at least 4 hours at the study center after Prime-2-CoV_Beta booster vaccination. After the last participant of each of the Cohorts 1 to 4 has completed 7 days of follow up after the Prime-2-CoV_Beta booster vaccination, all safety data will be reviewed by the safety review committee.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Prime-2-CoV_Beta, dose: 30 000 PFUs | Biological: Prime-2-CoV_Beta<br>* 1 intramuscular injection (1.0 mL each) into the deltoid muscle on Day 1<br>|
| Experimental: Cohort 2<br>Prime-2-CoV_Beta, dose: 300 000 PFUs | Biological: Prime-2-CoV_Beta<br>* 1 intramuscular injection (1.0 mL each) into the deltoid muscle on Day 1<br>|
| Experimental: Cohort 3<br>Prime-2-CoV_Beta, dose: 3 000 000 PFUs | Biological: Prime-2-CoV_Beta<br>* 1 intramuscular injection (1.0 mL each) into the deltoid muscle on Day 1<br>|
| Experimental: Cohort 4<br>Prime-2-CoV_Beta, dose: 150 000 000 PFUs | Biological: Prime-2-CoV_Beta<br>* 1 intramuscular injection (1.0 mL each) into the deltoid muscle on Day 1<br>|
| Experimental: Cohort 5<br>Prime-2-CoV_Beta, dose: 30 000 000 PFUs | Biological: Prime-2-CoV_Beta<br>* 1 intramuscular injection (1.0 mL each) into the deltoid muscle on Day 1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) throughout the study | All safety data will be summarized descriptively overall and by cohort. TEAEs will be summarized by descriptive statistics using contingency tables (counts of events, number and proportion of participants with events) and presented by system organ class and preferred term, as well as by severity. | Day 1 (vaccination day) to month 6 (end of study visit, ±14 days) | 
| Proportion of participants with solicited local adverse events (first 7 days after Prime-2-CoV_Beta booster vaccination): pain at injection site, redness, induration, and swelling. | Solicited local adverse events will be summarized by descriptive statistics using contingency tables (counts of events, number and proportion of participants with events). | Day 1 (vaccination day) to day 8 (Visit 3; ±1 day) | 
| Proportion of participants with solicited systemic adverse events (first 7 days after Prime-2-CoV_Beta booster vaccination): fever, fatigue, headache, chills, vomiting, nausea, diarrhea, new or worsened muscle pain, new or worsened joint pain. | Solicited systemic adverse events will be summarized by descriptive statistics using contingency tables (counts of events, number and proportion of participants with events). | Day 1 (vaccination day) to day 8 (Visit 3; ±1 day) | 
| Proportion of participants with unsolicited treatment-emergent adverse events throughout the study | All unsolicited adverse events which occur after the first administration of investigational product are defined as treatment-emergent adverse events. Treatment-emergent adverse events will be summarized by descriptive statistics using contingency tables (counts of events, number and proportion of participants with events) and presented by system organ class and preferred term, as well as by severity. | Day 1 (vaccination day) to month 6 (end of study visit, ±14 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Level of neutralizing antibody titers versus SARS CoV-2 (Wuhan wild type) at each post-booster vaccination assessment | Immunogenicity endpoints will be descriptively analyzed by cohort and visit. Separate analyses will be done for the different parameters, e.g., different antibodies evaluated with different serological immunogenicity assays. | Day 1 (vaccination day), day 8 (±1 day), day 15 (±2 days), day 29 (±1 day), month 3 (±14 days), month 6 (end of study visit, ±14 days) | 
| Geometric mean fold rise (GMFR) of neutralizing antibodies (versus Wuhan wild type) from Baseline to each post-booster vaccination assessment | The fold change from Baseline will be computed for each participant. The fold rise is calculated as the ratio of the post- vs pre-vaccination titer value. The fold change from Baseline will be summarized using descriptive statistics by cohort and visit. Additionally, the GMFR with 95% CI will be presented. | Day 1 (vaccination day), day 8 (±1 day), day 15 (±2 days), day 29 (±1 day), month 3 (±14 days), month 6 (end of study visit, ±14 days) | 
| IgG antibody titer versus SARS-CoV-2 receptor-binding protein | Immunogenicity endpoints will be descriptively analyzed by cohort and visit. Separate analyses will be done for the different parameters, e.g., different antibodies evaluated with different serological immunogenicity assays. | Day 1 (vaccination day), day 8 (±1 day), day 15 (±2 days), day 29 (±1 day), month 3 (±14 days), month 6 (end of study visit, ±14 days) | 
| Geometric mean titers (GMT) of receptor-binding protein-specific IgG antibodies | Immunogenicity endpoints will be descriptively analyzed by cohort and visit. Separate analyses will be done for the different parameters, e.g., different antibodies evaluated with different serological immunogenicity assays. | Day 1 (vaccination day), day 8 (±1 day), day 15 (±2 days), day 29 (±1 day), month 3 (±14 days), month 6 (end of study visit, ±14 days) | 
| Geometric mean fold rise of receptor-binding protein-specific IgG antibodies from Baseline | The fold change from Baseline will be computed for each participant. The fold rise is calculated as the ratio of the post- vs pre-vaccination titer value. The fold change from Baseline will be summarized using descriptive statistics by cohort and visit. Additionally, the geometric mean fold rise with 95% confidence interval will be presented. | Day 1 (vaccination day), day 8 (±1 day), day 15 (±2 days), day 29 (±1 day), month 3 (±14 days), month 6 (end of study visit, ±14 days) | 
| Proportion of participants with adverse events of special interest throughout the study | Adverse events of special interest will be summarized by descriptive statistics using contingency tables (counts of events,number and proportion of participants with events) and presented by system organ class and preferred term, as well as by severity. The frequency (% of participants) of adverse events of special interest throughout the study will be tabulated. | Day 1 (vaccination day) to day 8 (Visit 3; ±1 day) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, vaccine, Orf virus, SARS-CoV-2