PAN-TB consortium commences phase 2 clinical trial to evaluate two novel TB treatment regimes

SOUTH AFRICA — The Project to Accelerate New Treatments for Tuberculosis (PAN-TB), a global private-public partnership, has announced a phase 2b/c clinical trial, sponsored by the Bill & Melinda Gates Medical Research Institute (Gates MRI).

The trial will evaluate whether novel regimens that combine registered products and new chemical entities have the potential to effectively treat drug-sensitive TB (DS-TB) and inform the development of a “pan-TB” regimen capable of treating all forms of active pulmonary TB.

The regimens under evaluation are designed to explore shorter treatment durations compared to existing drug regimens, without the need for accompanying drug-resistance testing for individuals.

The goal is to identify a candidate regimen suitable for phase 3 development.

The trial has started in South Africa with 500 participants and subsequent trial sites are expected to launch in the Philippines in August and in Peru in 2024, pending national approvals.

The collaboration is evaluating two novel drug regimens comprising five antibacterial agents—bedaquiline, delamanid, pretomanid, quabodepistat, and sutezolid.

Specifically, the two different drug combos offer; the first is DBQS – delamanid, bedaquiline, quabodepistat and sutezolid, and the second PBQS – pretomanid, bedaquiline, quabodepistat and sutezolid.

In an interview, Charles Wells, head of therapeutics development at Gates MRI said, “With current treatment taking at least six months, it’s a particularly high burden for low- and middle-income countries where TB is very common.”

Wells added that if the consortium could come up with regimens that could do the job in half the time, what that would mean in these countries is huge.

Tuberculosis is one focus area for the Gates MRI, launched in Boston in 2018 to help kick-start new drugs, vaccines, and diagnostics for diseases that typically afflict the poorest countries and are often overlooked by drug companies.

The trial announcement comes exactly six weeks after the Gates Foundation and Wellcome committed US$550 million to fund a Phase III study of an experimental tuberculosis vaccine from GSK.

The shot could become the first new tuberculosis vaccine in over a century if the new 26,000-person study is successful.

PAN-TB phase 2b/c clinical trials specifications

The trial employs an innovative design that consists of two stages to assess the efficacy of the regimens and evaluate the potential to shorten treatment duration.

In the initial stage, the trial will enrol approximately 129 participants where the safety, tolerability, efficacy, and pharmacokinetics of the complete DBQS and PBQS regimens, with each drug administered daily for four months (17 weeks), will be evaluated in participants 18 to 65 years old with DS pulmonary TB.

Approximately 43 participants will receive the six-month (26 weeks) standard-of-care treatment for DS-TB in the countries where trial sites are located.

If successful, the second stage will enroll approximately 400 participants to test the selected regimen at shorter treatment durations, ranging from two to four months, across five arms.

An additional 30-40 participants will be enrolled in the standard-of-care arm for the second stage of this trial.

To support participants during their treatment, the trial integrates a Stop Treatment and Watch (STrAW) Concilium, a group made up of expert clinical consultants that will evaluate trial participants treatment response, blinded to the specific regimen they receive, and advise trial investigators on patient management.

The trial will utilize the best available tools including regular engagement with treatment support workers, direct observation of therapy with video technology, and medication reminder monitors.

A novel Biomarkers Strategy will inform promising new biomarkers with the aim of enabling faster access to data to monitor treatment outcomes for future trials.

The Project to Accelerate New Treatments for Tuberculosis

The Project to Accelerate New Treatments for Tuberculosis (PAN-TB) is a first-of-its-kind collaboration among philanthropic, non-profit and private sectors that aims to accelerate the development of an investigational drug regimen capable of treating all forms of tuberculosis.

The consortium members include the Gates MRI, the Bill & Melinda Gates Foundation, the nonprofit TB Alliance, and four pharmaceutical companies — Evotec, GSK, Johnson & Johnson, and Otsuka Pharmaceutical.

The PAN-TB collaboration plans to work closely and transparently with the European Regimen Accelerator for Tuberculosis (ERA4TB), which was launched in January 2020.

New molecular entities identified by ERA4TB that show promise in initial human studies could later be incorporated into the PAN-TB collaboration’s later-stage, clinical research.

Tuberculosis is the biggest infectious disease killer in the world, with roughly 10.6 million new cases and 1.6 million deaths reported in the most recent count in 2021.

The current treatment typically requires gruelling six-month courses of multiple antibiotics and has seen little change in nearly half a century.

The Bill & Melinda Gates Medical Research Institute is dedicated to advancing research and development in the field of global health. By sponsoring this clinical trial, they are taking an active role in finding innovative solutions to address the challenges posed by tuberculosis.

It is hoped that the findings from this trial will contribute to the development of new and improved treatment options for tuberculosis patients, ultimately leading to better health outcomes and a reduced global burden of the disease.

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