Zambia launches phase 3 clinical trial for promising TB vaccine candidate

ZAMBIA has demonstrated its commitment to eradicating Tuberculosis (TB) by launching phase 3 clinical
trial for a promising TB vaccine candidate.
The first trial site in Zambia is in Lusaka. Screening of participants started on August 29 at selected sites
in Lusaka. There will be a total of four clinical trial sites in Zambia.
TB remains a significant public health challenge in Zambia, with approximately 59,000 people afflicted
by the disease each year.
The disease mainly affects those living in poverty and with limited access to healthcare.
The need for an effective vaccine has never been more urgent than now, especially for adolescents and
adults in the country and globally who are most at risk.
Zambia is the third country to start Phase 3 clinical trials for this vaccine candidate, following Kenya in
July and South Africa in March.
Monde Muyoyeta is the national principal investigator for the trial in Zambia.
“We are excited to participate in this clinical trial, and look forward to working with our community,”
said Dr Muyoyeta of the Centre for Infectious Diseases Research in Zambia (CIDRZ).
“So many people continue to be burdened by TB, including the silent epidemic of post TB lung disease.
Personally, I am very hopeful that this pivotal trial will confirm the findings from Phase 2 trials,” Dr
Muyoyeta says.
At full capacity, the trial will include up to 20,000 participants, including people living with HIV, at 60
trial sites in seven countries — South Africa, Zambia, Malawi, Mozambique, Kenya, Indonesia and
Vietnam.
Participants will receive either the investigational M72/AS01E vaccine or a placebo in what is known as a
double-blind trial, meaning neither the trial participant nor the clinical investigators will know who
receives vaccine or placebo.
This approach is considered the gold standard for evaluating the safety and efficacy of an investigational
vaccine.
If shown to be well-tolerated and effective, M72/AS01E could potentially become the first vaccine to
help prevent pulmonary TB in adolescents and adults, the most common form of the disease, and the
first new TB vaccine in over a century.
It is anticipated that it will take up to five years to complete the trial, followed by data analysis and then
preparation for submission of data to regulatory authorities.
Globally, according to the World Health Organisation, an estimated 10.6 million people fell ill with TB in
2022 and 1.3 million died — over 3,500 people per day.
The disease primarily affects people in low- and middle-income countries, and those at highest risk are
often living in poverty, with poor living and working conditions and undernutrition.

Almost half of TB-affected households face costs higher than 20 percent of their household income. In
Zambia alone, around 59,000 people develop TB each year.
While TB is one of the world’s deadliest infectious diseases — and the leading cause of death amongst
people living with HIV — the only available TB vaccine, the Bacillus Calmette–Guérin (BCG), dates back
to 1921.
It protects babies and young children against severe forms of TB, but it offers inadequate protection for
adolescents and adults against the pulmonary form of the disease, which is primarily responsible for
transmission of the TB bacterium.
The Gates MRI, a nonprofit organisation and subsidiary of the Bill & Melinda Gates Foundation, is
sponsoring the trial, which is supported by funding from the Gates Foundation and Wellcome.
GSK continues to provide technical assistance to the Gates MRI, supplies the adjuvant component of the
vaccine for the Phase 3 trial and will provide the adjuvant post licensure should the trial be successful.
An adjuvant is an ingredient used in some vaccines that can help create a stronger immune response.
“The launch of this Phase 3 trial for a TB vaccine candidate in Zambia is a major step, and we thank our
global and Zambian colleagues for making this important undertaking possible,” said Dr. Alemnew
Dagnew, who leads development of M72/AS01E at the Gates MRI.
“TB continues to be a tragic burden on our communities, but we are committed to helping to address
this public health challenge,” Dr. Dagnew says.
The M72/AS01E vaccine candidate has been in development since the early 2000s. It was originally
designed and clinically evaluated by the biopharma company GSK up to the proof-of-concept phase
(Phase 2b), in partnership with Aeras and the International AIDS Vaccine Initiative (IAVI) and was funded
by GSK and in part by the Bill & Melinda Gates Foundation. In 2020, GSK announced a partnership with
the Gates MRI for further development of M72/AS01E.
In GSK’s Phase 2b trial, M72/AS01E provided approximately 50 percent protection (13/1626 versus
26/1663) against progression to active pulmonary tuberculosis for three years in Mycobacterium
tuberculosis-infected HIV-negative adults, which was unprecedented in decades of TB vaccine research.
The World Health Organisation estimates that over a 25-year time span, that level of protection could
save 8.5 million lives, prevent 76 million new TB cases and save US$41.5 billion for TB affected
households.
Making vaccines accessible and affordable for communities in areas of high disease burden in the long-
term is a priority for all trial partners.
The Gates MRI has worked with a wide range of stakeholders, including communities around clinical trial
sites, to guide the TB candidate vaccine to Phase 3.
To this end, the Gates MRI, GSK, Wellcome and the Gates Foundation are working together to
understand the potential demand for the vaccine and build an end-to-end plan to ensure long-term
sustainable access, should the trial be successful; from supporting research and building an evidence-
base for the potential impact of the vaccine and community requirements for uptake, to collaborating
with multilateral, regional and country partners required to introduce the vaccine.
Additionally, the trial funders are planning to establish an international advisory group comprised of
representatives from all these groups to provide input on the overall programme.

Developing and ensuring access to global health products is a complex task. As such, global collaboration
and strong partnerships are a core component of planning for future access to the candidate vaccine.
In March 2024, the Bill & Melinda Gates Medical Research Institute (Gates MRI) announced that a Phase
3 clinical trial to assess the efficacy of the M72/AS01E tuberculosis vaccine candidate was underway,
with first doses given in South

By Benedict Tembo