Trial to Evaluate the Immunogenicity of Dose Reduction Strategies of the MVA-BN Monkeypox Vaccine
Condition: Monkeypox
MeSH terms: Monkeypox
Intervention: JYNNEOS
Intervention description: JYNNEOS is FDA-approved and licensed as a smallpox and monkeypox vaccine in the United States. JYNNEOS is a live vaccine produced from the strain Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN), an attenuated, non-replicating orthopoxvirus. Each 0.5 mL dose is formulated to contain 0.5 x 10^8 to 3.95 x 10^8 infectious units of MVA-BN live virus in 10 mM Tris (tromethamine), 140 mM sodium chloride at pH 7.7. Subcutaneous is administered in the deltoid region, intradermal is administered in the volar aspect (inner side) of the forearm.
Intervention MeSH terms: Smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 229.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Dose Reduction; Immunogenicity; JYNNEOS; Monkeypox; MVA-BN; Open-Label; Randomized; Vaccine

Summary:

      This study is a Phase 2 randomized, open-label, non-placebo controlled, multi-site clinical
      trial that will evaluate two intradermal (ID) regimens for Modified Vaccinia Ankara-Bavarian
      Nordic (MVA-BN) vaccine compared to the standard subcutaneous (SC) regimen in healthy,
      vaccinia-naïve adults 18 to 50 years of age, inclusive. At least 210 participants will be
      enrolled and randomized to one of three study arms. The two dose sparing strategies include
      one-fifth (2 x 10^7) and one-tenth (1 x 10^7) of the standard dose of MVA-BN administered ID
      on Day 1 and 29 (Arm 1 and 2, respectively). The comparator arm (Arm 3) will be the 2-dose
      standard (1 x 10^8) MVA-BN SC regimen.

      The study will enroll a 1:1:1 randomization allocation. Participants will not be stratified
      by clinical trial site, demographic characteristics or human immunodeficiency virus (HIV)
      infection status; however, these data will be collected during screening and enrollment. Each
      participant may be screened either in a separate visit in the 7 days prior to Day 1 or on Day
      1.

      The primary hypothesis involves a two-step hierarchical process. The study will first test
      non-inferiority of the 2 x 10^7 ID regimen relative to 1 x 10^8 SC (standard dose regimen).
      If the 2 x 10^7 ID regimen is non-inferior to the standard dose regimen, hypothesis testing
      will proceed to test non-inferiority of the 1 x 10^7 ID regimen relative to the standard dose
      regimen.

      The primary objectives are: 1) to determine if peak humoral immune responses following an ID
      regimen of 2 x 10^7 50% Tissue Culture Infectious Dose (TCID50) MVA-BN are non-inferior to
      the licensed regimen of 1 x 10^8 MVA-BN administered SC; 2) to determine if peak humoral
      immune responses following an ID regimen of 1 x 10^7 TCID50 MVA-BN are non-inferior to the
      licensed regimen of 1 x 10^8 MVA-BN administered SC.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Individuals 18 - 50 years of age inclusive at the time of consent.

          2. Able to read the written informed consent, states willingness to comply with all study
             procedures, and is anticipated to be available for all study visits.

          3. Agreement to adhere to Lifestyle Considerations during the study.

          4. Females of reproductive potential who have sexual intercourse with males must agree to
             use highly effective contraception for at least 1 month prior to signing ICF and
             through Day 57.

          5. In good general health as evidenced by medical history, physical examination, and
             clinical judgement of the investigator to be in stable state of health.

             *Participants with pre-existing stable chronic medical conditions defined as
             conditions not requiring significant change in therapy or hospitalization for
             worsening disease in the 4 weeks prior to enrollment can be included at the discretion
             of the investigator. This includes stable, well-controlled HIV positive individuals.

          6. If HIV infected individual, they must be on suppressive Antiretroviral therapy (ART)
             for at least 6 months, report a cluster of differentiation 4 (CD4) count of greater
             than 350 cells/uL and no Acquired Immune Deficiency Syndrome (AIDS)-defining illness
             in the last year.

        Exclusion Criteria:

          1. Ever received a licensed or an investigational smallpox or monkeypox vaccine.

             *This includes Dryvax, Acam2000, LC 16 m8, Modified Vaccinia Ankara (MVA)-based
             vaccine candidate or licensed vaccines, and Jynneos, Imvamune or Imvanex).

          2. Any history of monkeypox, cowpox, or vaccinia infection.

          3. Close contact of anyone known to have monkeypox in the 3 weeks prior to signing
             Informed Consent Form (ICF).

          4. Immunocompromised as determined by the investigator.

          5. Recent or current use of any immunosuppressing medications in the 4 weeks prior to
             signing ICF.

             **Topical, ophthalmic, inhaled, intranasal and intraarticular corticosteroids are
             acceptable, but receipt of >/= 20 mg/day of prednisone or equivalent for >/= 14
             consecutive days in the 4 weeks prior to signing ICF is exclusionary.

          6. Pregnant or breast feeding.

          7. Received or plans to receive a live vaccine in the 4 weeks prior to signing ICF and 4
             weeks after each vaccination.

          8. Received or plans to receive any other vaccine in the 2 weeks prior to signing ICF
             through Day 43.

          9. Received experimental therapeutic agent or vaccine in the 3 months prior to signing
             ICF.

         10. Has known allergy or history of anaphylaxis or other serious adverse reaction to a
             vaccine or vaccine products.

             ***This includes individuals with history of severe allergic reaction to gentamicin,
             ciprofloxacin, chicken or egg protein.

         11. Has tattoos, scars, or other marks which would, in the opinion of the investigator,
             interfere with assessment of the vaccination site.

         12. Has any medical disease or condition that, in the opinion of the participating site
             Principal Investigator (PI) or appropriate sub-investigator, precludes study
             participation.

               -  This includes acute, subacute, intermittent, or chronic medical disease or
                  condition that would place the participant at an unacceptable risk of injury,
                  render the participant unable to meet the requirements of the protocol, or may
                  interfere with the evaluation of responses or the participant's successful
                  completion of this trial.