COVID-19
Conditions
Keywords
COVID-19, vaccine, Orf virus, SARS-CoV-2
Brief summary
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.
Detailed description
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. Initially, a total of 60 participants were planned to be vaccinated in 5 cohorts of 12 participants each. Dose ranging of Prime-2-CoV\_Beta was planned to be done by dose escalation with doses ranging from 3x104 plaque forming units (PFUs) up to 3x10\^7 PFUs. With protocol Version 7.0, Cohort 6 with 12 participants was added with 6x10\^7 PFU. With protocol Version 8.0, 1 additional cohort, Cohort 7 (1.2x10\^8 PFU, stratified by previous COVID-19 vaccinations and previous SARS-CoV-2 infections) with 24 participants will be added (total number thus 96 participants). Procedures for Cohorts 6 and 7 will be the same as for Cohorts 1 - 5, except that for some participants in Cohort 7 ORFV shedding in urine, saliva, blood, and stool will be evaluated.
Interventions
BIOLOGICALPrime-2-CoV_Beta
1 intramuscular injection (1.0 mL each) into the deltoid muscle on Day 1
Sponsors
University Hospital Tuebingen
FGK Clinical Research GmbH
VisMederi srl
Staburo GmbH
Viedoc Technologies AB
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
All cohorts 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 and 6 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Inclusion criteria 1. Healthy adult men or women aged 18 to 55 years 2. Previous COVID-19 vaccination and previous SARS-CoV-2 infection as follows: 1. Cohorts 1 to 7a: Full course of vaccination e.g., having received at least 3 doses of a licensed mRNA COVID-19 vaccine or having received at least 2 doses of a licensed mRNA COVID-19 vaccine and a prior SARS-CoV-2 infection, with the last dose of the vaccine being administered ≥ 10 weeks before Day 1 as documented in a respective vaccination certificate 2. Cohort 7b: No more than 2 doses of any licensed COVID-19 vaccine. Those with fewer COVID-19 vaccinations, preferably none or just one, will be given preference. Non-mRNA COVID-19 vaccines are acceptable. The last vaccine dose must have been given ≥ 10 weeks before Day 1 as documented in a respective vaccination certificate 3. Able to understand the participant information and providing written informed consent 4. Body mass index of 18.5 to 30.0 kg/m² and weight \> 50 kg at Screening 5. Women of childbearing potential must: 1. have a negative pregnancy test at Screening (blood) and at Day 1 (urine) 2. 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. 6. 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 1. 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 2. use adequate barrier contraception (male condom) during treatment with the investigational product until the end of the study, and 3. 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 4. use condoms during the entire study if they have a pregnant partner, to avoid exposure of the fetus to the investigational product 7. Willing and able to comply with all study procedures based on the investigator's judgment
Exclusion criteria
Previous and concomitant therapy: 1. 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 2. Previous vaccination against COVID-19 with vaccines (licensed or investigational) other than mRNA-based vaccines (licensed or investigational) only applicable for Cohorts 1 to 7a 3. 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) 4. Administration of immunoglobulins or any blood products within 2 months of Prime-2-CoV\_Beta booster vaccination 5. 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: 6. Active SARS-CoV-2 infection, confirmed by a commercially available SARS-CoV-2 rapid antigen test at Day 1, or currently on quarantine 7. {deleted} 8. 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 9. Known history of angioedema 10. Pregnant or lactating women 11. Any confirmed or suspected immunosuppressive or immunodeficient condition 12. Known history of Guillain-Barré Syndrome 13. Known infection with human immunodeficiency virus, hepatitis C virus or hepatitis B virus 14. Active cancer (malignancy) within 5 years before Day 1 (except for adequately treated non-melanomatous skin carcinoma, at the discretion of the investigator) 15. Moderate or severe illness and/or fever \> 38.0 °C within 1 week before Prime-2-CoV\_Beta booster vaccination 16. 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 17. 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) 18. History of mRNA vaccination-associated adverse events that were in nature and severity beyond the common AEs expected 19. 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 20. Current or history of chronic respiratory diseases, including mild asthma treated by on-demand medication (resolved childhood asthma is allowed) 21. Current or history of alcohol and/or drug abuse within the last 6 months before Day 1 Previous and concomitant clinical study experience 22. Current participation in another study or previous enrollment in this clinical study Other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) throughout the study | Day 1 (vaccination day) to month 6 (end of study visit, ±14 days) | 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. |
| 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. | Day 1 (vaccination day) to day 8 (Visit 3; ±1 day) | Solicited local adverse events will be summarized by descriptive statistics using contingency tables (counts of events, number and proportion of participants with events). |
| 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. | Day 1 (vaccination day) to day 8 (Visit 3; ±1 day) | Solicited systemic adverse events will be summarized by descriptive statistics using contingency tables (counts of events, number and proportion of participants with events). |
| Proportion of participants with unsolicited treatment-emergent adverse events throughout the study | Day 1 (vaccination day) to month 6 (end of study visit, ±14 days) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Level of neutralizing antibody titers versus SARS CoV-2 (Wuhan wild type) at each post-booster vaccination assessment | 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) | 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. |
| Geometric mean fold rise (GMFR) of neutralizing antibodies (versus Wuhan wild type) from Baseline to each post-booster vaccination assessment | 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) | 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. |
| IgG antibody titer versus SARS-CoV-2 receptor-binding protein | 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) | 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. |
| Geometric mean titers (GMT) of receptor-binding protein-specific IgG antibodies | 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) | 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. |
| Geometric mean fold rise of receptor-binding protein-specific IgG antibodies from Baseline | 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) | 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. |
| Proportion of participants with adverse events of special interest throughout the study | Day 1 (vaccination day) to day 8 (Visit 3; ±1 day) | 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. |
Countries
Germany
Contacts
PRINCIPAL_INVESTIGATORMeral Esen, Dr.
University Hospital Tübingen, Institute of Tropical Medicine
Outcome results
None listed