An Immunogenicity and Safety Trial of MVA-BN in Adults Living With HIV for the Prevention of Mpox Infection, in Kinshasa, DRC

Phase 2RecruitingNCT06839989

Institute of Tropical Medicine, Belgium600 enrolled

Overview

This is an open-label, phase 2, immunogenicity and safety trial of the MVA-BN vaccine for the prevention of mpox in adults living with HIV with different level of CD4 counts in Kinshasa, DRC. The study team aims to investigate whether the administration of 2 standard subcutaneous doses of the Modified Vaccinia Ankara of Bavarian Nordic (MVA-BN) vaccine given 28 days apart, is immunogenic and safe when administered to People Living with HIV (PLHIV) with different levels of CD4 counts in the Democratic Republic of the Congo (DRC). Enrollment will be stratified according to three different subgroups based on CD4 counts assessed during visit 1A: \<200 cells/µL; 200 to 499 cells/µL; ≥ 500 cells/µL. A total of 600 participants will be included in the trial, with 200 participants per subgroup. All participants will be invited to 6 trial visits over a period of 7 months. This study will take place in cooperation with the National Programme for the Fight against AIDS (PNLS), the 'Programme Elargi de Vaccination (PEV)' and the 'Institut National de Santé Publique (INSP)'. As part of the response to the current mpox epidemic in DRC, a large cohort of about 10,000 individuals living in Kinshasa will be vaccinated in this program. Vaccination will take place in the Centre Hospitalier Kabinda (CHK) and the Pakadjuma Health Centre. All people living with HIV (PLHIV) with the intention to be vaccinated in the CHK, will be asked for their willingness to participate in the MBOTE-HIVAX clinical trial until the sample size of 600 participants needed for this clinical trial is reached.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

600

Conditions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 45 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age ≥ 18 years and ≤ 45 years at time of informed consent * Able and willing to provide written informed consent * Infected with HIV and receiving combination antiretroviral therapy (ART) for ≥ 8 weeks prior to study entry and vaccination * Preparedness to follow the study schedule * Willingness to use contraception for 1 month after each vaccination (only for women of childbearing potential) Exclusion Criteria: * A known history of mpox and/or smallpox * A known history of vaccination with 1st, 2nd or 3rd generation smallpox vaccines, or vaccine platforms that contain MVA as a vector * Planned MVA-based vaccination (other than study vaccination) during the trial * Close contact to a confirmed mpox case in the 3 weeks prior to study enrollment * Uncontrolled severe infection or other condition requiring hospitalization * Pregnancy * History of anaphylaxis or severe allergic reaction to any vaccine or known allergy to one of the components of the study vaccine

Outcomes

Primary Outcomes

Seroconversion rates for monkeypox virus (MPXV) neutralizing antibodies

Seroconversion two weeks after administration of two standard doses of MVA-BN, defined as either the appearance of an MPXV neutralizing antibody titre (NT50) greater than or equal to the detection limit for initially seronegative participants or more than doubling of the antibody titre compared to baseline for participants seropositive at baseline

Time frame: 2 weeks after the last vaccine dose

Secondary Outcomes

Safety and reactogenicity of the MVA-BN vaccine in PLHIV

Solicited local AEs (pain, redness, swelling, induration, and itch at the injection site) and systemic AEs (generalized myalgia, headache, fatigue, nausea and/or vomiting, chills and/or fever (≥ 38.0°C)) up to day 14 post vaccination Unsolicited AEs up to day 14 post vaccination SAEs until the end of participation

Time frame: Up to day 14 and until end of participation

Seroconversion rates for vaccinia virus (VACV) neutralizing antibodies

Seroconversion two weeks after administration of two standard doses of MVA-BN, defined as either the appearance of an VACV neutralizing antibody titre (NT50) greater than or equal to the detection limit for initially seronegative participants or more than doubling of the antibody titre compared to baseline for participants seropositive at baseline.

Time frame: 2 weeks after last vaccine dose

Waning of MPXV neutralizing antibodies in PLHIV

The ratio between neutralizing antibody titre against MPXV at 6 months (D28 + 6M) versus 14 days (D28 + 14 days) after administration of two standard doses of MVA-BN.

Time frame: On day 14 and month 6

Waning of VACV neutralizing antibodies in PLHIV

The ratio between neutralizing antibody titre against VACV at 6 months (D28 + 6M) versus 14 days (D28 + 14 days) after administration of two standard doses of MVA-BN.

Time frame: On day 14 and month 6

Seroconversion rates and IgG antibody titre dynamics against MPXV and VACV antigens in serum

The absolute IgG antibody titre against the following antigens: A35R, H3L, B2R, A5L, A27L, B6R, E8L and A29L from mpox, and A33R and B5 from vaccinia virus at D14, D28 (second dose), D28+14d, D28+6M after administration of two standard doses of MVA-BN, be defined as either the appearance of Median Fluorescent Values (MFI) greater than the detection limit for initially seronegative participants or more than doubling of the antibody titre compared to baseline for participants seropositive at baseline.

Time frame: day 0 (prior to first dose), Day14, Day 28, Day 28+14 days, Day 28+6Months