An early clinical trial evaluating bacteriophage therapy in adults with cystic fibrosis begins

An early clinical trial evaluating bacteriophage therapy in adults with cystic fibrosis begins

Recruitment has begun for an early clinical trial evaluating bacteriophage therapy in adults with cystic fibrosis (CF) who carry Pseudomonas aeruginosa (P. aeruginosa) in their lungs. The study will examine whether bacteriophage, or “phage,” therapy is safe and can reduce the amount of bacteria in the lungs of volunteers. The study is being conducted by the Antiicrobial Resistance Leadership Group (ARLG) and funded by the National Institute of Allergy and Infectious Diseases. The researchers' goal is to enroll up to 72 adults at 16 CF centers across the United States.

Phages are viruses that can kill or neutralize certain bacteria while leaving non-target bacteria and human cells unharmed. For more than a century, researchers have considered the potential use of phages as therapeutics, anticipating that mixtures of bacteriophages could be used alone or in conjunction with antibiotics to treat bacterial infections, particularly those resistant to antibiotics.

P. aeruginosa, a serious and sometimes fatal bacterium commonly acquired in healthcare settings, is the most common bacterial cause of cystic fibrosis exacerbations. P. aeruginosa can exploit the tissue damage caused by CF changes in mucus to infect and colonize the lungs. Infections with multidrug-resistant P. aeruginosa are becoming increasingly common and only a handful of new antibiotics have been approved for their treatment in recent years.

“The spread of antibiotic resistance is concerning, and the need for more effective therapeutics for vulnerable populations such as people with cystic fibrosis is particularly urgent,” said Dr. Anthony S. Fauci, Director of the NIAID. “Although research into bacteriophage therapy may still be in its infancy in the United States, we hope that this and similar studies could open the doors to a new type of therapy for difficult-to-treat bacterial infections.”

The experimental phage therapeutic WRAIR-PAM-CF1 is manufactured by Adaptive Phage Therapeutics, Gaithersburg, Maryland. It contains a cocktail of four species of bacteriophage that naturally infect P. aeruginosa and take over its cellular processes, killing the bacterium. The phages in the cocktail are highly specific and do not attack human cells. They were cultured, cleaned and examined in detail in the laboratory. Genetic analyzes of these phages have shown that they do not carry harmful genes that could be inadvertently transferred to the bacteria they infect, such as genes that could confer antibiotic resistance.

The study will involve CF patients who chronically harbor P. aeruginosa in their airways. Participants will receive the phage cocktail as a single intravenous infusion at one of three dosage levels. Researchers will collect data on safety and microbiological activity; how the phages work in the body; how the cocktail affects participants' lung function; whether therapy for P. aeruginosa works differently in different geographical regions; and whether the therapy changes participants' overall quality of life.

The study will begin as a Phase 1b study and expand to a Phase 2 study. Initially, two participants per dosage level will receive an open-label infusion of the therapeutic agent and will then be closely monitored for four days. If no serious safety issues are identified, researchers will begin recruiting additional participants who will be randomly assigned to receive a single infusion of the therapeutic at one of three dosage levels or a placebo infusion. This part of the study will be double-blind, so neither the participants nor the investigators will know who is receiving the placebo. An evaluation of the safety and microbiological effect of the therapeutic will be conducted after eight participants complete each dosing. The results of this assessment will determine what dosage is administered in the next phase of the trial. The phase 2 study will involve up to 50 participants who will be randomly assigned to receive either the selected dose of the phage cocktail or a placebo. Each volunteer will have multiple follow-up visits to monitor their health and response to the experimental therapeutic.

The ARLG is an NIAID-supported clinical research consortium committed to combating the antibacterial resistance crisis and improving patient care. ARLG's mission is to prioritize, design and conduct clinical research that impacts the prevention, diagnosis and treatment of infections caused by antibiotic-resistant bacteria. For more information about this study, visit ClinicalTrials.gov and search for identifiers NCT05453578.

Source:

National Institutes of Health

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