Dose Ranging Trial to Assess Safety and Immunogenicity of V590 (COVID-19 Vaccine) in Healthy Adults (V590-001)
Condition: Coronavirus Disease (COVID-19)
MeSH terms: COVID-19
Intervention: V590; Placebo
Intervention description: Single dose of V590 administered via intramuscular (IM) injection with dosage levels of 5.00x10^5 pfu/mL (Panels A, E), 2.40x10^6 pfu/mL (Panels B,F), 1.15x10^7 pfu/mL (Panels C, G), 5.55x10^7 pfu/mL (Panels D, H, I).; Placebo administered via IM injection.
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: Double (Participant, Investigator)
Enrollment: 232.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The primary objective of this study is to evaluate the safety and tolerability of V590 versus
      placebo and to assess the immunogenicity of V590 on Day 28. The primary hypothesis is that at
      least one well-tolerated dose of V590 increases the geometric mean titers (GMTs) of
      anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike serum neutralizing
      antibody, as measured by plaque reduction neutralization test (PRNT), compared to placebo.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Is in overall good health based on medical history, physical examination, and vital
             sign (VS) measurements performed prior to randomization, as assessed by the
             investigator.

          -  Is in overall good health based on laboratory safety tests obtained at the screening
             visit.

          -  Has a body mass index (BMI) ≤30 kg/m2 inclusive (after rounding to the nearest whole
             number).

          -  Parts 1 and 2 (Panels A-H) only: Has negative testing for severe acute respiratory
             syndrome coronavirus 2 (SARS-CoV-2) based on both antibody and reverse transcription
             polymerase chain reaction (RT-PCR), at screening and upon start of domiciling.

          -  Part 3 (Panel I) only: Has positive serology (antibody) testing for SARS-CoV-2, also
             with negative SARS CoV-2 RT-PCR testing at screening and upon start of domiciling, and
             without symptoms of respiratory infection for at minimum 3 weeks preceding screening.

          -  Has been practicing social distancing for at least two weeks prior to planned start of
             domiciling and has had no close contacts with known active SARS-CoV-2 infection in
             that time period.

          -  Is male or female, from 18 years to 54 years of age inclusive (Parts 1 and 3 [Panels
             A-D, I]) or ≥ 55 years of age (Part 2 [Panels E-H]) at the time of signing the
             informed consent.

          -  Male participants are eligible to participate if they agree to the following during
             the intervention period and for at least 2 months after administration of study
             intervention: be abstinent from heterosexual intercourse as their preferred and usual
             lifestyle and agree to remain abstinent OR agree to use contraception unless confirmed
             to be azoospermic (vasectomized or secondary to medical cause).

          -  A female participant is eligible to participate if she is not pregnant or
             breastfeeding, and at least one of the following conditions applies: is not a woman of
             childbearing potential (WOCBP), or is a WOCBP and using an acceptable contraceptive
             method, or is abstinent from heterosexual intercourse as their preferred and usual
             lifestyle. A WOCBP must have a negative highly sensitive pregnancy test before the
             first dose of study intervention. If a urine test cannot be confirmed as negative, a
             serum pregnancy test is required.

        Exclusion Criteria:

          -  Has a known hypersensitivity to any component of V590 or placebo.

          -  Has any known or suspected active clinically significant autoimmune disease or
             immunosuppressive condition, acquired or congenital, as determined by medical history
             and/or physical examination.

          -  Has thrombocytopenia or other coagulation disorder contraindicating intramuscular
             vaccination or repeated venipuncture.

          -  Has history or current evidence of any condition, therapy, laboratory abnormality, or
             other circumstance that might expose the participant to risk by participating in the
             study, confound the results of the study or interfere with the participant's
             participation for the full duration of the study.

          -  Has a history of ongoing liver disease or, at the time of screening, has any one of
             the following: Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >
             1.5 × Upper Limit of Normal (ULN), alkaline phosphatase and direct bilirubin > ULN
             (total bilirubin may be up to 2 × ULN as long as direct bilirubin is equal to or below
             the ULN), or prothrombin time (PT) international normalized ratio (INR) > 1.25.

          -  Has a history of asthma or allergic asthma that required systemic corticosteroids in
             the previous year.

          -  Has a history of Guillain-Barré syndrome.

          -  Has a history of diabetes mellitus, requiring medication at the time of assessment, OR
             has a hemoglobin A1c ≥ 6.5.

          -  Has a history of any medical condition that would put the participant at risk for
             severe SARS-CoV-2 disease as judged by the investigator.

          -  Has any ongoing, symptomatic, acute or chronic illness requiring medical or surgical
             care or any condition that is immunosuppressive.

          -  Is mentally or legally incapacitated, has significant emotional problems at the time
             of screening visit or expected during the conduct of the study or has a history of
             clinically significant psychiatric disorder of the last 5 years.

          -  Has a history of cancer (malignancy).

          -  Participant has an estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m^2.

          -  Has a history of significant multiple and/or severe allergies or has had an
             anaphylactic reaction or significant intolerability to a vaccine or prescription or
             non-prescription drugs or food as judged by the investigator.

          -  Is positive for hepatitis B surface antigen, hepatitis C antibodies or human
             immunodeficiency virus (HIV)-1 or 2 antibodies. Individuals with antibodies to
             hepatitis C may be enrolled if hepatitis C viral load is negative and there is no
             evidence of or history of liver disease.

          -  Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4
             weeks prior to the pre-study (screening) visit.

          -  A WOCBP who has a positive urine or serum pregnancy test before vaccination.

          -  A WOCBP who is breastfeeding.

          -  Has any unstable chronic medical condition, including one that has resulted in change
             in therapy (medication or other) in the 30 days prior to randomization or
             hospitalization in the previous year or might be predicted to result in
             hospitalization in the year after enrollment.

          -  Has received or is expected to receive any SARS-CoV-2 vaccine or other coronavirus
             vaccine during the study (except V590), is using investigational agents for
             prophylaxis of SARS-CoV-2 or is taking any systemic antiviral medications.

          -  Has received any intra-articular steroid injections within the 3 months prior to study
             vaccination or is expected to require intra-articular steroid injection during the
             study.

          -  Is receiving immunosuppressive therapy or has received immunosuppressive therapy
             within 6 months of enrollment.

          -  Has received a blood transfusion or blood products, including immunoglobulin, in the 3
             months before anticipated study vaccination.

          -  Is expected to be receiving or is currently receiving antipyretic or analgesic
             medication on a daily or every other day basis from randomization through Day 7

          -  Has ever participated in an investigational study of a SARS-CoV-2 vaccine, a
             coronavirus vaccine, or an antiviral or other biologic product intended for the
             treatment of COVID-19.

          -  Has participated in another vaccine study within 3 months prior to screening or has
             participated in an investigational study within 4 weeks prior to the screening visit.

          -  Has ever received a vaccine based on vesicular stomatitis virus (VSV).

          -  Has a Fridericia's corrected time from Q wave to T wave (QTcF) interval >470 msec
             (male) or >480 msec (female), has a history of risk factors for Torsades de Pointes,
             or has uncorrected hypokalemia or hypomagnesemia.

          -  Is under the age of legal consent.

          -  Is smoking or vaping and/or has a history of chronic smoking or vaping within
             approximately six months prior to planned vaccination.

          -  Does not agree to follow the alcohol restrictions

          -  Has a tattoo, scar, or other physical finding at the area of the vaccination site that
             would interfere with intramuscular injection or a local tolerability assessment.

          -  Is a regular user of any illicit drugs or has a history of drug (including alcohol)
             abuse within approximately 1 year.

          -  Presents any concern by the investigator regarding safe participation in the study or
             for any other reason the investigator considers the participant inappropriate for
             participation in the study.

          -  Lives in a nursing home or long-term care facility.

          -  Is currently working in an occupation with high risk of exposure to SARS-CoV-2 (e.g.,
             health care worker with direct patient contact, emergency response personnel).