Phase 3 TB vaccine trial gets under way
The Bill & Melinda Gates Medical Research Institute (Gates MRI) has launched the final stage of clinical trials to test a potentially game-changing tuberculosis (TB) vaccine that scientists hope will be the first new shot against the disease in more than a century.
SA’s high TB burden and strong clinical trial infrastructure has positioned it to play a key role in the phase 3 trial, which aims to enrol 20,000 volunteers. The trial begins in SA, with volunteers to follow in Zambia, Malawi, Mozambique, Kenya, Indonesia and Vietnam.
The study will test the efficacy of the M72/AS01E candidate vaccine originally developed by pharmaceutical giant GlaxoSmithKline. A phase 2b trial of the jab found it offered 50% protection against pulmonary TB in HIV-negative people who already had latent disease. The phase 3 trial will include people living with HIV.
“If those figures can be replicated, the implications would be absolutely huge. [It] would be a game changer,” said the study’s principal investigator for SA, Lee Fairleigh, the director of maternal and child health at the Wits Reproductive Health and HIV Institute (Wits RHI). There was strong interest in volunteering for the trial from communities hard-hit by TB as many people had direct experience of the devastating effects of the disease, she said.
TB is SA’s leading cause of death with about 280,000 new cases diagnosed each year. Two thirds of SA adults are estimated to have latent TB, which can convert to active infection at a later stage. A TB vaccine that provided 50% protection could save 8.5-million lives, prevent 76-million new TB cases and save $41.5bn for TB-affected households, according to the World Health Organisation.
Trial participants will receive two doses one month apart of either the investigational vaccine or a placebo, with neither they nor the clinical trial researchers knowing which shot they got. This “double-blind” approach is considered the gold standard for evaluating the safety and efficacy of candidate vaccines. The candidate vaccine contains the M72 recombinant fusion protein, derived from two Mycobacterium tuberculosis antigens, combined with Glaxo’s proprietary adjuvant system, AS01E.
The Bacille Calmette Guérin (BCG) vaccine routinely given to babies worldwide to protect them from TB was launched in 1921. It contains weakened, live Mycobacterium bovis, which causes TB in animals and provides limited protection against TB that wanes by adolescence.
Glaxo halted its work on M72/AS01E more than 10 years ago, saying it did not see a viable market. It subsequently passed the licence on to the Gates MRI, a nonprofit spin-off from the Bill & Melinda Gates Foundation, which partnered with global charity Wellcome to continue work on the shot. The phase 3 trial is expected to last five years but work is already under way to ensure high-burden countries have access to the vaccine should it prove successful, said Gates MRI CEO Emilio Emini.
“We cannot find ourselves in a situation, as has been the case in the past, where we demonstrate efficaciousness of a vaccine and then we find have to wait years to make the investments in manufacturing to make it available” he said.
The director of infectious disease at Wellcome, Alex Pym, said: “While it is a long journey to results, the start of this trial in SA brings us a critical step closer to having an effective vaccine to protect those most at risk of TB. Global collaboration with regulators, in-country decision makers and communities affected is crucial if those who need it most are to benefit from this vaccine, should the trial be successful.”