Safety and immune response of a COVID-19 booster vaccine in healthy adults

A Phase I/IIa, 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

This will test a single Prime-2-CoV_Beta booster injection to see if it is safe and increases immune responses in healthy adults aged 18–55 who have had previous COVID vaccination or infection.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 96 (estimated)
• Ages: 18 Years to 55 Years
• Sex: All
• Sponsor: University Hospital Tuebingen (Academic / other)
• Drugs / interventions: prednisone
• Locations: 2 sites (Tübingen, Baden-Wurttemberg and 1 other locations)
• Trial ID: NCT05389319 on ClinicalTrials.gov

What this trial studies

This open-label, first-in-human, dose-finding trial will give one intramuscular booster dose of Prime-2-CoV_Beta and monitor participants for safety and immune responses. Healthy adults meeting predefined prior vaccination or infection criteria will be followed with in-person visits on Days 4, 8, 15, 29 and Months 3 and 6, plus phone checks on Days 2 and 3. Dose escalation will explore doses from 3×10^4 PFU up to 1.2×10^8 PFU across up to seven cohorts, with a planned total of up to 96 participants after amendments. For the highest-dose cohort, additional testing will include evaluation of Orf virus shedding in urine, saliva, blood, and stool.

Who should consider this trial

Good fit: Healthy adults aged 18–55 with documented prior COVID-19 vaccination and/or prior SARS-CoV-2 infection who meet BMI and other inclusion criteria and can attend scheduled visits at the German sites are the intended participants.

Not a fit: People outside the 18–55 age range, those with significant medical conditions or immunosuppression, pregnant people, or anyone who received a COVID vaccine within 10 weeks are unlikely to be eligible or to benefit from participating.

Why it matters

Potential benefit: If successful, this booster could safely increase antibody and cellular immunity against SARS-CoV-2 and add a new option for COVID-19 boosting.

How similar studies have performed: While many booster studies have shown additional doses raise antibody levels, the Orf virus–based Prime-2-CoV_Beta booster is first-in-human and largely untested in people.

Eligibility criteria

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 exclusion criteria
23. 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
24. Prolonged exposure to sheep or goats (e.g., shepherds, sheep farmer)

Where this trial is running

Tübingen, Baden-Wurttemberg and 1 other locations

• University Hospital Tübingen, Institute of Tropical Medicine — Tübingen, Baden-Wurttemberg, Germany (Recruiting)
• Bernhard-Nocht-Institut für Tropenmedizin — Hamburg, Free and Hanseatic City of Hamburg, Germany (Recruiting)

Study contacts

• Principal investigator: Meral Esen, Dr. — University Hospital Tübingen, Institute of Tropical Medicine
• Study coordinator: University Hospital Tübingen

Conditions COVID-19; vaccine; Orf virus; SARS-CoV-2