This double-blind, randomised, phase 3 non-inferiority trial (n=6,940) compared VPM1002 (recombinant BCG) vs. standard BCG vaccine in healthy newborns (0–14 days old) across 14 sites in sub-Saharan Africa, with up to 48 months of follow-up, to assess prevention of *M. tuberculosis* infection defined by QuantiFERON-TB Gold Plus (QFT) conversion.
VPM1002 did not demonstrate non-inferiority to BCG: QFT conversion occurred in 184/3,471 (5.3%) infants in the VPM1002 group vs. 150/3,469 (4.3%) in the BCG group (HR 1.23, 95% CI 0.99–1.53; non-inferiority threshold upper bound <1.25 not met). Serious adverse events and deaths were similar between groups, with no vaccine-related serious adverse events in either arm.
- The trial was underpowered: only 334 of 632 planned QFT conversion events accrued despite extending follow-up to 48 months, reducing statistical certainty. - The VPM1002 group had ~33% higher household TB exposure, introducing imbalance that could confound the primary endpoint. - The proportional hazards assumption was violated when TB exposure was included as a covariate, limiting reliability of the HR estimate.
VPM1002 cannot currently be recommended over standard BCG for TB prevention in newborns based on this trial. Clinicians and TB programmes should continue using BCG vaccination in neonates while awaiting further evidence on next-generation TB vaccines.
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