- Design
- Phase 3, double-blind, randomised, active-controlled non-inferiority trial
- Population
- 6,940 newborns in sub-Saharan Africa, including 720 HIV-exposed
- Primary outcome
- M. tuberculosis infection by QuantiFERON conversion
- Effect
- 5.3% vs 4.3%, HR 1.23 (95% CI 0.99 to 1.53); non-inferiority not shown
A phase 3 double-blind trial randomised 6,940 newborns at sites across sub-Saharan Africa, including 720 born to mothers with HIV, to VPM1002 or standard BCG. The primary endpoint was tuberculosis infection, defined as QuantiFERON (IGRA) conversion.
Over a median 35 months, conversion occurred in 5.3% with VPM1002 and 4.3% with BCG (HR 1.23, 0.99 to 1.53), missing the non-inferiority margin of 1.25. Safety profiles were similar with no vaccine-related serious adverse events. The trial stopped early with 334 of 632 planned events, and household tuberculosis exposure was about a third higher in the VPM1002 group.
VPM1002 has been of particular interest in India, where it has been studied for other uses. This trial does not support replacing BCG at birth, but it is not a clean negative either. It also shows how hard infection endpoints are in infant vaccine trials.
- Continue routine BCG at birth
- Do not treat VPM1002 as a proven replacement for neonatal BCG
- Remember IGRA conversion is a surrogate, not disease
- Household exposure remains the dominant driver of infant infection; screen contacts
Why it matters
A leading candidate to improve on BCG failed its first phase 3 test in infants, leaving neonatal protection unchanged.
Don't overread it
The trial was underpowered and imbalanced for exposure; it does not show VPM1002 is worse than BCG.
The statistics, in plain English
Non-inferiority required the upper bound of the confidence interval to be below 1.25. It reached 1.53, so the trial could not rule out that VPM1002 is meaningfully worse. The lower bound of 0.99 also means it could not show it was worse. With only 53% of the planned events, the trial simply lacked precision.
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