Today, the Infectious Disease Research Institute (IDRI) and Wellcome Trust announce the start of a Phase 2a trial in South Africa of IDRI's tuberculosis (TB) vaccine candidate, which has been shown to both prevent and treat TB in preclinical studies in animal models. The Wellcome Trust awarded IDRI a $5.8 million/ £3.8 million grant to clinically assess the ability of IDRI's vaccine candidate to reduce TB recurrence after treatment. Even after successfully completing an anti-TB treatment regimen, patients may succumb to TB again, thereby threatening TB control programs by promoting spread and drug resistance. Prior Phase 1 clinical trials have shown that IDRI's TB vaccine candidate boosts immune responses that may protect against TB recurrence.
Stephen Caddick, Ph.D., Director of Innovations at the Wellcome Trust, said: "TB is one of a number of serious infections that is becoming harder to treat as the bacteria evolve resistance to even our most effective drugs. We urgently need new ways of preventing and treating the infection in high-risk populations. The trial of this promising experimental vaccine is an important development, and one which could eventually give us a 21st century weapon against this centuries old disease." Funding from the Wellcome Trust will support an initial phase 2a safety and immunogenicity clinical trial involving 60 participants in South Africa, which has one of the highest burdens of TB in the world with almost 1 in 100 people developing active TB each year. A larger phase 2b efficacy trial, for which IDRI is seeking additional funding, is planned to start in 2017 with 900 participants.
"The Phase 2a trial will be the first dose-escalating TB vaccine trial conducted in persons who have previously had active TB and been successfully treated with a full course of antibiotic therapy," said Rhea Coler, Ph.D., Vice President of Preclinical Development for IDRI, who is serving as the Clinical Immunology Director for the trial. "This is an important study population as the incidence of TB can be higher in people recently cured of the disease." According to Coler, prior studies show that 5-8 percent of the population in the area where the clinical trial takes place relapse within one year, continuing the cycle of TB.
Mycobacterium tuberculosis, the bacteria that causes tuberculosis, lies dormant in one-third of the world's population, and activation results in one of the world's deadliest infectious diseases, killing 1.5 million and causing illness in 9 million during 2013 alone. The currently available TB vaccine, Bacille Calmette-Guérin (BCG), developed 90 years ago, reduces the risk of severe forms of TB in early childhood but is not effective once a person reaches adolescence or in any person with a positive tuberculin skin test. BCG also varies in effectiveness across the globe, particularly in developing countries where the burden is greatest. "The reason that BCG is ineffective in certain populations cannot be answered definitively, even after decades of research," Coler said. "The interaction between environmental mycobacteria and BCG vaccination has been considered as a possible cause for variations in protection, and there is a hypothesis that genetic or nutritional factors might influence the immune response or that immunity simply wanes over time. No matter the reason for BCG's lack of effectiveness, the issue remains the same: we need a new vaccine for TB."
Treating the disease has also proved challenging, with an increasing number of diagnosed multidrug-resistant cases making TB more difficult to control and multiplying the cost and time it takes to treat patients. The disease costs the global economy an estimated $1 billion every day.
IDRI's TB vaccine candidate has been designed by IDRI scientists to recognize both active TB (when a person has TB disease, is infectious and is suffering from symptoms of the disease, such as fever, coughing and weight loss), and latent TB (when a person is infected with M. tuberculosis but is not symptomatic and is not infectious).
The candidate, ID93 + GLA-SE, is composed of a recombinant fusion-protein antigen plus IDRI's proprietary adjuvant, GLA-SE, and has been previously tested in humans. Conducted in the U.S., the first phase 1 trial assessed the safety, tolerability and immunogenicity of the vaccine in 60 healthy adult volunteers with no prior exposure to BCG or M. tuberculosis. The second Phase 1 clinical trial was conducted in South Africa in 66 healthy volunteers, who were BCG vaccinated, with or without latent infection with M. tuberculosis. Both studies showed that ID93 + GLA-SE is safe and elicits a multi-functional immune response. The vaccine is intended to boost the immune response elicited by BCG, and could be used both to prevent TB infection and as a post-exposure vaccine.
IDRI's vaccine candidate has also shown additional potential advantages. "Our candidate shows efficacy against both drug-resistant and drug-sensitive strains of M. tuberculosis in animal studies and has also demonstrated efficacy in drug-shortening regimens," said Coler.
Funding for preclinical development and testing of ID93 + GLA-SE to this point has come from a variety of sources, including the National Institutes of Health, Paul G. Allen Family Foundation, the Bill & Melinda Gates Foundation and Aeras.
"TB is one of the most widespread, persistent and deadly global health problems in the world today," said Steve Reed, Ph.D., Founder, President and Chief Scientific Officer for IDRI. "We are very pleased to partner with the Wellcome Trust on this study to prevent disease recurrence, a particularly important issue with TB. And as we move this vaccine candidate along in development, we are at the same time transferring production technology to South Africa, where we can support development of Africa's biotechnology industry and manufacture products where they are needed most."
This project continues longstanding collaborations among seven South African research groups at the forefront of clinical and immunological TB research (with particular strengths in TB therapeutics, TB vaccinology and mycobacterial immunity); a leading European immunology group (Leids Universitair Medisch Centrum); IDRI, the vaccine developer; and the Wellcome Trust, which has invested in the development of IDRI's TB vaccine candidate through its Translation Fund. The South African Tuberculosis Vaccine Initiative and the Desmond Tutu HIV Center, both at the University of Cape Town, along with the TASK Research Centre in Cape Town, serve as sites for the study, with assistance from the Immunology Research Group at Stellenbosch University in South Africa.
About IDRI: As a nonprofit global health organization, IDRI (Infectious Disease Research Institute) takes a comprehensive approach to combat infectious diseases, combining the high-quality science of a research organization with the product development capabilities of a biotech company to create new diagnostics, drugs and vaccines. Founded in 1993, IDRI has 125 employees headquartered in Seattle with nearly 100 partners/collaborators around the world. http://www.idri.org
About the Wellcome Trust: The Wellcome Trust is a global charitable foundation dedicated to improving health. We provide more than £700 million a year to support bright minds in science, the humanities and the social sciences, as well as education, public engagement and the application of research to medicine.
Our £18 billion investment portfolio gives us the independence to support such transformative work as the sequencing and understanding of the human genome, research that established front-line drugs for malaria, and Wellcome Collection, our free venue for the incurably curious that explores medicine, life and art. http://www.wellcome.ac.uk