Phase 3, Randomised Maternal and Infant (From 4 to 24 Months of Age) Safety and Immunogenicity Trial of MVA-BN® Vaccine in the Democratic Republic of the Congo
This Phase 3 double-blinded, randomized study aims to evaluate the safety and immunogenicity of the two-dose MVA-BN mpox vaccine regimen, administered subcutaneously, in infants and children aged 4 to 24 months in the Democratic Republic of the Congo (DRC), a population at high risk of mpox infection and complications. The study will compare the safety and immunogenicity of a full-dose regimen versus a half-dose regimen in this population. A hierarchical testing strategy will be applied as follows: first, non-inferiority of the full-dose regimen in infants/children (4-24 months old) will be evaluated against the full-dose regimen in adults from the POX-MVA-045 study. If non-inferiority is demonstrated, the immunogenicity of the half dose in infants/children (4-24 months old) will subsequently be tested for non-inferiority vs the full dose in adult. The trial will be conducted in Boende, Tshuapa Province, DRC. The trial plans to enroll 344 male and female infants/children, who will be randomized to receive two doses of the MVA-BN vaccine administered 28 days apart. Participants in Child Group 1 (N=172) will receive the standard vaccine dose (0.5 mL), while those in Child Group 2 (N=172) will receive half the standard dose (0.25 mL), with both groups following the same dosing schedule. This study builds on positive safety and immunogenicity data from prior trials that support the use of the standard dose regimen in younger children. However, considering the developmental differences in the immune systems of infants and young children/adolescents, it aims to evaluate whether a half-dose regimen can provide similar immunogenicity while potentially reducing reactogenicity. The findings will offer valuable insights into the optimal dosing strategy for this age group, balancing safety and immunogenicity to inform future vaccination recommendations.
• The participant must be between 4 and 24 months old upon enrolment.
• The participant's parent or legal guardian must pass (≥9/10) the TOU after being advised of the risks and benefits of the trial in a language understood by the parent/guardian and before performing any trial-specific procedures.
• \- Note: If the participant's parent or guardian fails the TOU test on the first attempt, he/she must be retrained on the purpose of the study and must take the test again (2 repeats are allowed). If the participant's parent/guardian fails on the third attempt, the screening or consenting procedures should not continue.
• The participant's parent or guardian must sign and date the informed consent form after reading the form and being advised of the risks and benefits of the trial in a language understood by the participant and before performing any trial-specific procedures.
• The participant must live in the Boende health zone or its surrounding health zones in the Tshuapa province of the DRC.
• The participant must be generally healthy in the investigator's clinical judgment and on the basis of vital signs assessed at day 1 screening with no severe (chronic) conditions (as far as medically known) that might interfere with vaccine assessment.
• \- Note: HIV-positive subjects can be enrolled as long as their general condition is good, i.e., they are on antiretroviral treatment or have no signs or symptoms of immunosuppression, diagnosed on the basis of physical examination, medical history, and the investigator's clinical judgment.
• The participant's parent(s) or guardian(s) of the child must agree to follow the study protocol, including attending follow-up visits and reporting any adverse events.
• The participant must be available and his/her parent(s) or guardian(s) must be willing to have their child participate for the duration of the study.
⁃ The participant's parent(s) or guardian(s) must be willing to provide verifiable identification and have means to be contacted (phone number or address).