Abstract
SummaryBackgroundNew tuberculosis (TB) vaccines are being developed to combat the global epidemic. A phase IIb trial of a candidate vaccine, MVA85A, was conducted in a high burden setting in South Africa to evaluate proof-of-concept efficacy for prevention of TB in infants.ObjectiveTo describe the study design and implementation lessons from an infant TB vaccine efficacy trial.MethodsThis was a randomised, controlled, double-blind clinical trial comparing the safety and efficacy of MVA85A to Candin control administered to 4–6-month-old, BCG-vaccinated, HIV-negative infants at a rural site in South Africa. Infants were followed up for 15–39 months for incident TB disease based on pre-specified endpoints.Results2797 infants were enrolled over 22 months. Factors adversely affecting recruitment and the solutions that were implemented are discussed. Slow case accrual led to six months extension of trial follow up.ConclusionThe clinical, regulatory and research environment for modern efficacy trials of new TB vaccines are substantially different to that when BCG vaccine was first evaluated in infants. Future infant TB vaccine trials will need to allocate sufficient resources and optimise operational efficiency. A stringent TB case definition is necessary to maximize specificity, and TB case accrual must be monitored closely.
Highlights
New tuberculosis (TB) vaccines are being developed to combat the global epidemic
The secondary objectives were: 1) to evaluate the efficacy of the MVA85A vaccine compared to placebo control in the prevention of TB disease using three clinical endpoints, 2) the evaluation of the immunogenicity of MVA85A compared to controls and 3) the evaluation of the rate of Mycobacterium tuberculosis (Mtb) infection, as defined by QuantiFERON TB Gold (in-tube) test (QFT) conversion at final study assessment in MVA85A recipients compared to controls in infants without a diagnosis of TB disease during the trial
This increased the pool of staff available to conduct informed consent which led to an increase in enrolment rates
Summary
A phase IIb trial of a candidate vaccine, MVA85A, was conducted in a high burden setting in South Africa to evaluate proof-of-concept efficacy for prevention of TB in infants. Methods: This was a randomised, controlled, double-blind clinical trial comparing the safety and efficacy of MVA85A to Candin control administered to 4e6-month-old, BCG-vaccinated, HIV-negative infants at a rural site in South Africa. One of these novel vaccines, MVA85A, is a recombinant strain of Modified
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