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

NCT06844487 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: PIPVac-001 Infant Component
• Study Type: interventional
• Target: 344
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Mpox (Monkeypox); Vaccination; Safety; Infants; Children; Immunogenicity

Keywords

MVA-BN; Monkeypox virus; mpox; Infants; Children; Non-inferiority testing; Paediatric; Phase 3; Vaccine; Smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic; Randomised

Outcome Measures

Primary Outcomes (2)

• Immunogenicity of Full-Dose vs. Half-Dose MVA-BN Vaccine in Infants/Children.

  Compare the immunogenicity of full-dose and half-dose MVA-BN vaccine regimens in infants/children (4-24 months), with neutralising antibody responses measured by PRNT assays 14 days post-second dose, against the full-dose regimen in adults from the POX-MVA-045 study. 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.

  14 days after the second dose

• Safety and Reactogenicity of the MVA-BN Vaccine in Infants/Children Compared to Adults from the POX-MVA-045 Study

  Evaluate the safety and reactogenicity of the standard MVA-BN regimen administered subcutaneously to infants/children (4-24 months), compared to the standard regimen in adults from the POX-MVA-045 study. Safety endpoints include SAE, AESI, MAAE, and AE occurrences; reactogenicity endpoints include solicited local and systemic events.

  Throughout the trial period; from the first dose to one year after the second dose

Secondary Outcomes (6)

• Immunogenicity of Standard and Half-Dose Regimens in Infants/Children vs. Adults and Older Children.

  From baseline to one year after the second dose

• Total Binding Antibody Response in Infants/Children vaccinated with MVA-BN Vaccine standard regimen and adults and children of the POX-MVA-045 study

  From baseline to one year after the second dose

• Immunogenicity of Standard vs. Half-Dose Regimens in Infants/Children.

  From baseline to one year after the second dose

• Total Binding Antibody Response with Standard vs. Half-Dose Regimens in Infants/Children.

  From baseline to one year after the second dose

• Safety and Reactogenicity of Standard vs. Half-Dose MVA-BN Vaccine in Infants/Children.

  Throughout the trial period; from the first dose to one year after second dose

Other Outcomes (4)

• Impact of Demographic Variables on Neutralising Antibody Responses in Infants/ Children Vaccinated with Half-Dose Regimen

  From enrolment to one year after the second dose

• Impact of Demographic Variables on Total Binding Antibody Responses with Standard Regimen

  From enrolment to one year after the second dose

• Neutralising Antibody Response in Standard and Half-Dose Regimens in a Subset of Infants/Children.

  From baseline to one year after the second dose

Study Arms (3)

Child group 1

ACTIVE COMPARATOR

Male or Female infants/children aged 4-24 months will be administered each vaccine of the MVA-BN standard or half-dose regimen (depending on the randomisation group) by SC administration into the anterolateral thigh. For children closer to 24 months old, the deltoid of the upper arm can also be used (preferably the nondominant arm, if already known).

Biological: MVA-BN standard regimen

Child group 2

ACTIVE COMPARATOR

Male of female infants/children aged 4-24 months will be administered each vaccine of the MVA-BN standard or half-dose regimen (depending on the randomisation group) by SC administration into the anterolateral thigh. For children closer to 24 months old, the deltoid of the upper arm can also be used (preferably the nondominant arm, if already known).

Biological: MVA-BN half-dose regimen

Historical arm

OTHER

Historical data from healthy adults aged 18 to 50 years old, and children aged 2 to \<12 years old from the POX-MVA-045 study (NCT06549530), will be used for safety and immunogenicity comparisons. These participants will be vaccinated in the deltoid of the upper arm.

Biological: MVA-BN standard regimen

Interventions

MVA-BN standard regimen BIOLOGICAL

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.

Child group 1; Historical arm

MVA-BN half-dose regimen BIOLOGICAL

The MVA-BN vaccine, with the active ingredient: Modified Vaccinia Ankara-Bavarian Nordic, will be administered as two half doses of the standard regimen; meaning infants/children allocated to Child Group 2 will receive 0.25 mL of the 0.5 mL. 1x10\^8 TCID50 Inf.U./0.5 mL standard regimen. The doses will be given 28 days apart (±3 days) via subcutaneous injection into the deltoid muscle, preferably in the non-dominant arm. Only one vial will be used per infant/child.

Child group 2

Eligibility Criteria

• Age: 4 Months - 24 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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).

You may not qualify if:

• The child is excluded if their mother received the MVA-BN vaccine during her pregnancy with the child or during the immediate postpartum period while breastfeeding the child.
• Known history of cowpox, mpox or vaccinia infection.
• Close contact in the 2 weeks prior to signing the ICF with anyone known to have mpox.
• Having received any smallpox or licensed or investigational poxvirus-based (e.g. ACAM2000, MVA-BN based like MVA-BN-Filo) vaccine in the past.
• Must not have received another experimental or non-licensed vaccine within 4 weeks before receiving the MVA-BN vaccine and during the trial.
• Known allergy or history of anaphylaxis or other severe adverse reactions to vaccines or vaccine products (including any of the constituents of the study vaccines), including known allergy to egg, egg products and aminoglycosides.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, e.g., tris(hydroxymethyl)-amino methane, including a history of allergic asthma.
• Acute or chronic medical condition that, in the opinion of the investigator, would render the trial procedures unsafe or would interfere with the evaluation of responses, including but not limited to neurologic, cardiovascular, respiratory, hepatic, hematologic, rheumatologic, endocrine, gastrointestinal, renal, autoimmune, or immunosuppressive conditions.
• \- Note: Participants with minor acute illnesses such as mild diarrhoea or mild upper respiratory tract infection or temperature ≥38.0ºC at screening will be excluded from enrolment at that time but may be rescheduled for re-screening later if feasible.
• Presence of significant medical conditions or clinically significant findings at screening or vital signs for which, in the opinion of the gynaecologist, participation would not be in the best interest of the participant (e.g., compromise the safety or well-being) or that could prevent, limit, or confound the protocol-specified assessments.
• Note: Participants who have recently received treatment for acute, uncomplicated malaria are eligible for participation if at least 3 days have elapsed from the conclusion of a standard, recommended course of therapy for malaria; participants who are acutely ill with malaria at the time of screening should complete therapy and wait an additional 3 days after completion before screening for the study.
• Note: Participants with sickle cell trait can be included.
• History of malignancy (e.g., leukaemia, lymphoma).
• Chronic administration (defined as more than 14 days) of systemic high dose immune-suppressant drugs (2 mg/kg/day or more of prednisolone or its equivalent or 20 mg/day or more for children who weigh more than 10 kg) from 6 months prior to first trial vaccination to trial conclusion.
• Major surgery (per the investigator's judgment) within the 4 weeks before screening or planned major surgery during the study (from the start of screening onwards).

Sponsors & Collaborators

• European and Developing Countries Clinical Trials Partnership (EDCTP): collaborator
• Jean-Pierre Van geertruyden: lead
• Ace Africa: collaborator
• PENTA Foundation: collaborator
• Bavarian Nordic: collaborator
• University of Kinshasa: collaborator
• CEPI: collaborator

Study Sites (1)

Boende Hôpital Général de Référence, Boende

Boende, La Tshuapa, Democratic Republic of the Congo

Location

Related Publications (8)

• Lemey G, Lariviere Y, Zola TM, Maketa V, Matangila J, Mitashi P, Vermeiren P, Thys S, De Bie J, Muhindo HM, Ravinetto R, Van Damme P, Van Geertruyden JP. Algorithm for the support of non-related (serious) adverse events in an Ebola vaccine trial in the Democratic Republic of the Congo. BMJ Glob Health. 2021 Jun;6(6):e005726. doi: 10.1136/bmjgh-2021-005726.

  PMID: 34183329 BACKGROUND

• Zola Matuvanga T, Lariviere Y, Lemey G, De Bie J, Milolo S, Meta R, Esanga E, Vermeiren PP, Thys S, Van Geertruyden JP, Van Damme P, Maketa V, Matangila J, Mitashi P, Muhindo-Mavoko H. Setting-up an Ebola vaccine trial in a remote area of the Democratic Republic of the Congo: Challenges, mitigations, and lessons learned. Vaccine. 2022 May 31;40(25):3470-3480. doi: 10.1016/j.vaccine.2022.04.094. Epub 2022 May 9.

  PMID: 35550847 BACKGROUND

• Puri A, Pollard AJ, Schmidt-Mutter C, Laine F, PrayGod G, Kibuuka H, Barry H, Nicolas JF, Lelievre JD, Sirima SB, Kamala B, Manno D, Watson-Jones D, Gaddah A, Keshinro B, Luhn K, Robinson C, Douoguih M; EBL4001 Study Group. Long-Term Clinical Safety of the Ad26.ZEBOV and MVA-BN-Filo Ebola Vaccines: A Prospective, Multi-Country, Observational Study. Vaccines (Basel). 2024 Feb 17;12(2):210. doi: 10.3390/vaccines12020210.

  PMID: 38400193 BACKGROUND

• Lariviere Y, Zola T, Stoppie E, Maketa V, Matangila J, Mitashi P, De Bie J, Muhindo-Mavoko H, Van Geertruyden JP, Van Damme P. Open-label, randomised, clinical trial to evaluate the immunogenicity and safety of a prophylactic vaccination of healthcare providers by administration of a heterologous vaccine regimen against Ebola in the Democratic Republic of the Congo: the study protocol. BMJ Open. 2021 Sep 28;11(9):e046835. doi: 10.1136/bmjopen-2020-046835.

  PMID: 34588237 BACKGROUND

• Poland GA, Kennedy RB, Tosh PK. Prevention of monkeypox with vaccines: a rapid review. Lancet Infect Dis. 2022 Dec;22(12):e349-e358. doi: 10.1016/S1473-3099(22)00574-6. Epub 2022 Sep 15.

  PMID: 36116460 BACKGROUND

• Beeson AM, Haston J, McCormick DW, Reynolds M, Chatham-Stephens K, McCollum AM, Godfred-Cato S. Mpox in Children and Adolescents: Epidemiology, Clinical Features, Diagnosis, and Management. Pediatrics. 2023 Feb 1;151(2):e2022060179. doi: 10.1542/peds.2022-060179.

  PMID: 36471498 BACKGROUND

• Sanchez Clemente N, Coles C, Paixao ES, Brickley EB, Whittaker E, Alfven T, Rulisa S, Agudelo Higuita N, Torpiano P, Agravat P, Thorley EV, Drysdale SB, Le Doare K, Muyembe Tamfum JJ. Paediatric, maternal, and congenital mpox: a systematic review and meta-analysis. Lancet Glob Health. 2024 Apr;12(4):e572-e588. doi: 10.1016/S2214-109X(23)00607-1. Epub 2024 Feb 21.

  PMID: 38401556 BACKGROUND

• Bunge EM, Hoet B, Chen L, Lienert F, Weidenthaler H, Baer LR, Steffen R. The changing epidemiology of human monkeypox-A potential threat? A systematic review. PLoS Negl Trop Dis. 2022 Feb 11;16(2):e0010141. doi: 10.1371/journal.pntd.0010141. eCollection 2022 Feb.

  PMID: 35148313 BACKGROUND

Related Links

• MVA-BN
• MVA-BN Product Characteristics

MeSH Terms

Conditions

Mpox, Monkeypox; Smallpox

Condition Hierarchy (Ancestors)

Poxviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Primate Diseases; Animal Diseases; Rodent Diseases

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr

Model Details: 344 male or female infants/children will be randomised (1:1) to receive the two doses of the standard MVA-BN vaccine, administered 28 days apart (N= 172), or two half doses of the standard MVA-BN vaccine, administered 28 days apart (N= 172).

Study Record Dates

• First Submitted: February 19, 2025
• First Posted: February 25, 2025
• Study Start: May 29, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): May 1, 2027
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)