A Phase 1/2 clinical trial, called CYPHY, to evaluate the phage therapy YPT-01 in treating chronic Pseudomonas aeruginosa infections in people with cystic fibrosis (CF) has been initiated at Yale University.
This double-blind, placebo-controlled study (NCT 04684641) aims to enroll 36 adult patients with these chronic infections. Additional information and trial contacts are available here.
P. aeruginosa is a bacteria that can cause serious lung infections in people with CF. While antibiotics can effectively treat some infections, many bacteria evolve resistance to commonly used antibiotics, which can make treatment difficult.
YPT-01 is an inhaled therapy that uses bacteriophages (phages for short) — viruses that can infect and kill bacteria. The specific viruses included in the therapy were selected based on their safety, efficacy against P. aeruginosa, and their ability to reduce virulence and antibiotic resistance.
The YPT-01 phages were also selected to drive evolutionary trade-offs, such that, in order for the bacteria to evolve resistance to the phages, they need to also evolve to be less virulent or less able to cause disease.
“We know that pathogens evolve resistance to any antibiotic or therapy we use, so our approach turns that to our advantage,” Paul Turner, PhD, a professor at Yale and co-inventor of YPT-01, said in a press release. “By targeting phage to mechanisms of virulence, we ensure that if pathogens evolve resistance to phage, they lose traits that make them effective pathogens, putting them in an evolutionary Catch-22.”
Turner is also the co-founder of Felix Biotechnology, which holds an exclusive license from Yale for YPT-01.
CYPHY (CYstic Fibrosis bacterioPHage Study at Yale) will test the safety and efficacy of YPT-01 at two dose levels compared with a placebo, plus standard antimicrobial therapy.
Its primary efficacy goal is a reduction in bacterial load as seen in sputum culture at 14 days after the start of treatment. Placebo-group patients may move to YPT-o1 as an add-on treatment following completion of the trial’s blinded portion.
Researchers will also assess whether the therapy can reduce virulence and antibiotic-resistance in P. aeruginosa bacteria.
Besides making it easier to treat infections in individual patients, reducing bacterial virulence and antibiotic-resistance may prove beneficial for the healthcare system as a whole, by creating evolutionary pressures that make bacteria in healthcare settings less of a danger to people.
“Phage therapies have been used for over a century but for various reasons clinical trials to demonstrate their efficacy have been unsuccessful. In designing CYPHY, we learned from those studies to develop best practices for a truly blinded, randomized, placebo-controlled phage therapy trial. But most importantly, this study aims to help patients,” said Ben Chan, PhD, a research scientist at Yale and co-inventor of YPT-01.
YPT-01 was previously given to 12 patients with chronic and multi-drug resistant infections via emergency authorization from the U.S. Food and Drug Administration.
“If the data from this trial reflect earlier human data showing safety and efficacy, we will focus on moving this asset into a larger commercial trial as soon as possible,” said Rob McBride, CEO of Felix Biotechnology.
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