NCT06844500

Phase 3 Maternal Safety & Immunogenicity Trial of MVA-BN® in DRC

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

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 359 (estimated)
• Sponsor: Jean-Pierre Van geertruyden · Academic / Other
• Sex: Female
• Age: 16 Years – 35 Years
• Healthy volunteers: Accepted

Summary

This Phase 3 open-label study aims to assess the safety and immune response of the MVA-BN mpox vaccine when administered subcutaneously to pregnant and postpartum women in the Democratic Republic of the Congo (DRC), a population at high risk of mpox infection. The study will be conducted in Boende, Tshuapa Province, DRC. A total of 359 maternal participants, aged 16 to 35 and in their second or third trimester of pregnancy, will be enrolled. Participants will be randomly assigned to receive two subcutaneous doses of the MVA-BN vaccine, given 28 days apart, either during pregnancy (Maternal Group 1) or within 72 hours after delivery (Maternal Group 2). Additionally, pregnant women in any trimester who have been recently exposed to a confirmed mpox case will be enrolled in the post-exposure prophylaxis (PEP) arm (Maternal Group 3), receiving the vaccine as soon as possible after exposure-ideally within four days but up to 14 days if they remain asymptomatic. The study will evaluate the safety, reactogenicity, and immune responses of vaccinated pregnant women compared to healthy adults in the POX-MVA-045 study (NCT06549530) through non-inferiority analyses. Participants will be monitored for immunogenicity and safety for 13 months post-delivery, while neonates will be observed for safety over the same period. The trial will also compare outcomes between women vaccinated during pregnancy and those vaccinated postpartum, assess the transfer of maternal immunity to neonates, and explore correlations between maternal antibody levels in serum and breast milk. This study seeks to provide strong evidence supporting the safety and immunogenicity of the MVA-BN mpox vaccine in pregnancy, contributing to global public health efforts to protect at-risk women and their infants in mpox-endemic regions.

Detailed description

This open-label, Phase 3 study aims to evaluate the immunogenicity and safety of the MVA-BN standard regimen (1x10⁸ TCID50 Inf.U./0.5mL) administered subcutaneously in two doses, 28 days apart, to pregnant women and women in the immediate postpartum period (\<72 hours after delivery). As described in the study protocol, the main study consists of the vaccination and safety and immunogenicity follow-up of pregnant and postpartum women. A sub-study will evaluate the transmission of antibodies from mother to child either during pregnancy of via breast milk. The trial plans to enrol 359 participants, aged 16 to 35 years, with a gestational age between 13 and 32 weeks. Participants will be randomised into three groups: Maternal Group 1 (N=215), vaccinated during pregnancy; Maternal Group 2 (N=144), vaccinated within 72 hours postpartum; and Maternal Group 3 (N=convenience sampling), which includes pregnant women exposed to a confirmed mpox case within the past 14 days but who remain asymptomatic and will be offered post-exposure prophylaxis (PEP). The study will be conducted at the General Reference Hospital of Boende, located in Boende, Tshuapa Province, Democratic Republic of Congo (DRC), with two satellite sites (Motema Mosantu and Marie-Louise Health Centres) supporting maternal delivery, vaccination for Maternal Group 2, and immediate postpartum sample collection, where applicable. During the screening visit (SCR), interested participants will undergo an evaluation (test of understanding) to ensure understanding of the study and provide informed consent (or assent for minors). Demographics, vaccination history, and medical history will be recorded. Participants' general health will be evaluated through a physical examination, urine testing, and a gynaecological ultrasound to confirm gestational age. Blood samples will be collected for haematology, biochemistry, and infection screening for HIV, hepatitis B, syphilis, and malaria. After enrolling participants will be randomised to Maternal Group 1 or Maternal Group 2, unless they have been exposed to mpox in the past 14 days, then they will enrolled in Maternal group 3. All AEs, including serious adverse events (SAEs), medically attended adverse events (MAAEs), and adverse events of special interest (AESIs), will be monitored from enrolment until 13 months after delivery. The prenatal visits (PN) are scheduled according to gestational age: PN Visit 1 (15-18 weeks), PN Visit 2 (24-28 weeks), PN Visit 3 (28-32 weeks), and PN Visit 4 (36-38 weeks). The number of visits will depend on the participant's enrolment date. Where feasible and applicable, prenatal visits will be combined with screening and/or vaccination visits. At each visit, vital signs and anthropometric measurements (weight, height, and fundal height) will be recorded to monitor maternal health and foetal growth. Urinary tests for infections will be performed at each visit, and a glucose challenge test (GCT) at 24-28 weeks will screen for gestational diabetes. Ultrasounds will also be performed as needed to evaluate gestational health. All participants will receive Intermittent Preventive Treatment for malaria (IPTp) according to WHO guidelines, with doses spaced at least one month apart. On Day 0, participants' vital signs (blood pressure, heart rate, respiratory rate, and temperature) will be assessed. Blood samples will be collected from mothers to establish baseline immunogenicity, including neutralising antibodies (PRNTs), total binding antibodies (ELISA), and IgG binding antibodies (LUMINEX assay) against vaccinia and mpox viruses. To minimise inconvenience and where possible and applicable, samples for haematology and biochemistry will be collected simultaneously. Afterwards, participants will receive their first dose of the MVA-BN vaccine and a participant journal to record any solicited or unsolicited adverse events (AEs). Seven days after the first vaccine dose (Day 0), the participant will be asked to return with the journal to record data on solicited AEs and unsolicited AEs (UAEs). Ongoing solicited AEs at this visit will be followed up until resolution and UAEs will be followed up until 28 days post-vaccination and inquired about before the second vaccine dose. On Day 28, physical examinations of the mother will be conducted. Participants will receive the second MVA-BN vaccine dose, and blood samples will be collected from mothers to measure neutralising antibodies (PRNTs), total binding antibodies (ELISA), and IgG binding antibodies (LUMINEX assay). Participants will also receive a second participant journal to record any AEs. Seven days after the first vaccine dose (Day 35), the participant will be asked to return with the journal to record data on solicited AEs and unsolicited AEs (UAEs). Ongoing solicited AEs at this visit will be followed up until resolution and UAEs will be followed up until 28 days post-vaccination during a telephone or home visit on Day 56. On Day 42, blood samples will be collected from mothers to evaluate the persistence of vaccine-induced antibodies. On Day 56, ongoing solicited AEs will be followed up and any ongoing or new UAEs be assessed/followed up via telephone or home visit. On delivery day (Dd), a cord blood sample will be collected to measure neutralising antibodies (PRNTs), total binding antibodies (ELISA), and IgG binding antibodies (LUMINEX assay). Within 72 hours postpartum, colostrum (breast milk) samples will be collected to measure IgA antibody levels using the LUMINEX assay, reflecting maternal immunity transfer through breastfeeding. Physical examinations of both the mother and neonate will be conducted. Neonatal assessments will include APGAR scores at 1 and 5 minutes, general appearance, measurements (weight, length, and head circumference), and reflexes. Maternal assessments will focus on recovery and any postpartum complications. Maternal Group 2 will be vaccinated within 72 hours postpartum with the first MVA-BN dose, this will be Day 0 for this Group. All other visits from Day 0-Day 56 will take place for this group as described above. The Day 42 visit corresponds with the 6 week post-partum visit. Activities for both visits will be combined in to one visit. Post-delivery visits will occur at 6 weeks, 12 weeks, 6 months and 13 months post delivery for all participants. Mothers and neonates will undergo follow-up assessments, including physical examinations of neonates to evaluate growth and developmental milestones. Blood samples will be collected from mothers at each visit to monitor the durability of vaccine-induced antibodies. Additionally, breast milk samples will be collected on at 6 weeks, 12 weeks, 6 months and 13 months post delivery to evaluate IgA binding antibody levels. At 6 weeks and 12 weeks postpartum visits, IgG binding antibodies in breast milk will also be determined. Blood samples from neonates will be collected on at 6 weeks, 12 weeks and 6 months after birth to assess neutralising antibodies (PRNTs), total binding antibodies (ELISA), and IgG binding antibodies (LUMINEX assay).

Conditions

• Neonate
• Maternal Transmission
• Mpox
• Vaccination
• Immunogenicity
• Safety
• Pregnancy
• Postpartum

Interventions

Type	Name	Description
BIOLOGICAL	MVA-BN standard regimen	The MVA-BN vaccine, with the active ingredient: Modified Vaccinia Ankara-Bavarian Nordic, will be administered as a standard two-dose regimen at 1x10\^8 TCID50 Inf.U./0.5 mL. The doses will be given 28 days apart (±3 days) via subcutaneous injection into the deltoid muscle, preferably in the non-dominant arm.
BIOLOGICAL	MVA-BN standard regimen (Administered as PEP)	MVA-BN. Post Exposure Prophylaxis (PEP) The MVA-BN vaccine, with the active ingredient: Modified Vaccinia Ankara-Bavarian Nordic, will be administered as a standard two-dose regimen at 1x10\^8 TCID50 Inf.U./0.5 mL. The doses will be given 28 days apart (±3 days) via subcutaneous injection into the deltoid muscle, preferably in the non-dominant arm. For Maternal Group 3, MVA-Bn will be administered as PEP as soon as possible after exposure, preferably within 4 days after exposure. However, as per WHO guidelines, PEP will be offered up to 14 days after exposure if the pregnant woman has not yet developed symptoms.

Timeline

• Start date: 2025-06-23
• Primary completion: 2026-06-01
• Completion: 2027-05-01
• First posted: 2025-02-25
• Last updated: 2026-01-30

Locations

1 site across 1 country: Democratic Republic of the Congo