Research Summary

VPM1002 TB Vaccine Does Not Meet Noninferiority to BCG in Newborns

Edited by:
Ashton L. Stahl

Key Highlights

  • The phase 3 trial enrolled 6,950 newborns across 14 sites in sub-Saharan Africa.
  • QFT conversion occurred in 5.3% of infants assigned to VPM1002 and 4.3% assigned to BCG.
  • VPM1002 did not meet the prespecified noninferiority criterion compared with BCG.
  • Adverse event profiles were similar, with no vaccine-related serious adverse events reported.

VPM1002, a recombinant bacille Calmette-Guérin (BCG) vaccine, did not demonstrate noninferiority to BCG for preventing Mycobacterium tuberculosis infection among infants in sub-Saharan Africa. Investigators conducted the active-controlled trial at 10 main sites and 4 satellite sites across rural and urban settings in sub-Saharan Africa. Healthy newborns aged 0 to 14 days with a birthweight of at least 2.3 kg were randomly assigned in a 1:1 ratio to receive a single 0.05-mL intradermal dose of VPM1002 or BCG. The primary endpoint was incident QuantiFERON-TB Gold Plus (QFT) conversion, assessed every 6 months beginning at month 6. Noninferiority required the upper bound of the hazard ratio’s 95% CI to be less than 1.25.

Study Findings

Between November 9, 2020, and June 21, 2022, investigators enrolled 6,950 infants. After 10 withdrawals, 6,940 infants were randomly assigned, including 720 born to mothers living with HIV and 6,220 HIV-unexposed infants. The intention-to-treat population included 3,449 male and 3,491 female infants. Overall, 6,897 infants were vaccinated: 3,452 with VPM1002 and 3,445 with BCG.

During a median follow-up of 35 months, QFT conversion occurred in 184 of 3,471 infants (5.3%) assigned to VPM1002 and 150 of 3,469 infants (4.3%) assigned to BCG. The hazard ratio for VPM1002 versus BCG was 1.23 (95% CI, 0.99-1.53). Since the upper confidence limit exceeded the prespecified margin of 1.25, VPM1002 did not meet the noninferiority criterion.

Adverse event profiles, including serious adverse events and deaths, were similar between the groups. No vaccine-related serious adverse events were reported.

Clinical Implications

According to the study authors, the findings demonstrate the challenges of using interferon-γ release assay–defined infection endpoints in infant tuberculosis vaccine trials. Although VPM1002 did not demonstrate noninferiority for the primary endpoint, the investigators stated that the study lacked sufficient statistical certainty to definitively compare the vaccines.

The trial ended early in October 2024 since only 334 of the planned 632 infections occurred, despite extending follow-up to 48 months. The authors also identified discordance between QFT conversion and confirmed tuberculosis endpoints, approximately a 33% higher household tuberculosis exposure in the VPM1002 group, and a violation of the proportional hazards assumption when tuberculosis exposure was included as a covariate.

Expert Commentary

“These findings highlight challenges in using IGRA-defined infection endpoints in infant vaccine trials,” the researchers concluded.

Reference

Nduba V, Mathebula M, Nankabirwa V, et al; priMe Consortium. Comparison of VPM1002 with BCG in the prevention of tuberculosis in newborn infants: a multicentre, double-blind, randomised, phase 3, non-inferiority trial. Lancet Infect Dis. Published online August 18, 2026. doi:10.1016/S1473-3099(26)00374-9