Safety and Tolerability of COVID-19 Vaccine (ABNCoV2)
Condition: Covid19; Severe Acute Respiratory Syndrome; SARS-CoV-2 Infection
MeSH terms: COVID-19; Severe Acute Respiratory Syndrome
Intervention: ABNCoV2 Vaccine
Intervention description: SARS-CoV-2 vaccine
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: ABNCoV2 is a virus-like particle vaccine. It will be administered as two intramuscular injections in groups of up to 9 volunteers. All subjects will receive a second vaccination with the same dose and formulation 4 weeks following the first vaccination. The pre-defined escalation schedule will start with 6 μg ABNCoV2, followed by 12, 25 and 50 μg with a maximum dose of 70 μg. MF59-adjuvanted and non-adjuvanted formulations will be tested in parallel to detect superiority or futility of the MF59-adjuvanted against the non-adjuvanted formulation at the 6, 12 and 25 μg dosage. Approval for further dose escalation and choice of adjuvant use will be provided by a safety monitoring committee (SMC), supported by pre-defined analyses of safety, tolerability and immunogenicity data at day 14 post-first-vaccination. Recruitment for the two best (safe, tolerable and most immunogenic) regimens will continue until 12 volunteers per regimen have been immunized.
Masking: None (Open Label)
Enrollment: 45.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      This phase 1 trial aims to assess the safety and tolerability of two doses of ABNCoV2,
      formulated with and without the adjuvant MF59, in healthy adult volunteers and to identify
      the dosage and formulation that optimizes the immunogenicity-tolerability ratio 14 days
      following first vaccination with ABNCoV2.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subject must sign written informed consent to participate in the trial.

          2. Subject is able to understand planned study procedures and demonstrate comprehension
             of the protocol procedures and knowledge of the study by passing a quiz (assessment of
             understanding). Subjects must score at least 80% correct on a multiple-choice quiz. If
             they do not score 80% on the initial quiz, the protocol information will be reviewed
             with them, and they will have the opportunity to retest.

          3. In the opinion of the investigator, the subject can and will comply with the
             requirements of the protocol.

          4. Subjects are available to attend all study visits and are reachable by phone
             throughout the entire study period from day -1 until 24 weeks following last
             vaccination (end of study).

          5. Subject is a male or non-pregnant and non-lactating female age ≥ 18 and ≤ 55 years and
             in good health at time of ABNCoV2 administration.

          6. Subject agrees to their general practitioner (GP) being informed about participation
             in the study and agrees to sign a form to request the release by their GP, and medical
             specialist when necessary, of any relevant medical information concerning possible
             contra-indications for participation in the study to the investigator(s).

          7. The subject agrees to refrain from blood donation to Sanquin or for other purposes
             throughout the study period according to current Sanquin guidelines.

          8. Female subjects of non-childbearing potential may be enrolled in the study.
             Non-childbearing potential is defined as pre-menarche, current bilateral tubal
             ligation or occlusion, hysterectomy, bilateral ovariectomy or post-menopause. All
             other female subjects must agree to use continuous adequate contraception2 for the
             duration of the study. Female subjects must have a negative pregnancy test at the
             inclusion visit.

        Exclusion Criteria:

        Any clinically significant abnormal finding on clinical examination or laboratory screening
        tests according to the US Food and Drug Administration (FDA) Toxicity Grading Scale for
        Healthy Adult and Adolescent Subjects Enrolled in Preventative Vaccine Clinical Trials
        [30].

        2. History of COVID-19 infection. 3. Chronic use of immunosuppressive drugs or other immune
        modifying drugs within six months prior to study onset (inhaled and topical corticosteroids
        and oral anti-histamines exempted) or expected use of such during the study period.

        4. Positive urine toxicology test for cannabis, cocaine or amphetamines at inclusion.

        5. Screening tests positive for SARS-CoV-2, SARS-CoV-2 antibodies, Human Immunodeficiency
        Virus (HIV), active Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV).

        6. Receipt of any investigational or non-registered product (drug or vaccine) other than
        the study product in the 30 days preceding enrolment or during the study period.

        7. Participation in any other clinical study in the 30 days prior to the start of the study
        or during the study period.

        8. Immunization with any vaccines within the past four weeks or planned receipt of a
        vaccine during the study period with the exception of a licensed SARS-CoV-2 vaccine, given
        within the framework of the national SARS-CoV-2 vaccination campaign. The time between last
        vaccination with ABNCoV2 and a SARS-CoV-2 vaccine provided by the campaign shall be at
        least 4 weeks.

        9. Known hypersensitivity to any of the vaccine components (adjuvant or protein).

        10. Administration of immunoglobulins and/or any blood products within the three months
        prior to the first dose of ABNCoV2 or planned administration during the study period.

        11. Previous participation in a COVID-19 vaccine study. 12. Body Mass Index (BMI) >35
        kg/m2. 13. Pregnancy, lactation or intention to become pregnant during the study period.

        14. History of drug or alcohol abuse interfering with normal functioning in the five years
        preceding enrolment.

        15. Being an employee or student of the department of Medical Microbiology of the
        Radboudumc, or a person otherwise related to the investigator other than a professional
        relationship for clinical trial purpose only.

        16. Any other condition or situation that would, in the opinion of the investigator, place
        the subject at an unacceptable risk of injury or render the subject unable to meet the
        requirements of the protocol.