Safety and microbiological activity of phage therapy in persons with cystic fibrosis colonized with Pseudomonas aeruginosa: study protocol for a phase 1b/2, multicenter, randomized, double-blind, placebo-controlled trial

• Published in: Current controlled trials in cardiovascular medicine 2022-12, Vol.23 (1), p.1057-12, Article 1057
• Main Authors: Tamma, Pranita D, Souli, Maria, Billard, Michael, Campbell, Joseph, Conrad, Douglas, Ellison, Damon W, Evans, Beth, Evans, Scott R, Greenwood-Quaintance, Kerryl E, Filippov, Andrey A, Geres, Holly S, Hamasaki, Toshimitsu, Komarow, Lauren, Nikolich, Mikeljon P, Lodise, Thomas P, Nayak, Seema U, Norice-Tra, Carmelle, Patel, Robin, Pride, David, Russell, Janie, Van Tyne, Daria, Chambers, Henry F, FowlerJr, Vance G, Schooley, Robert T
• Format: Article
• Language: English
• Subjects: Adult; Anti-Bacterial Agents; Antibiotics; Bacteria; Bacterial infections; Care and treatment; Clinical trials; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Complications and side effects; Cystic fibrosis; Cystic Fibrosis - therapy; Development and progression; Double-Blind Method; Double-blind studies; Drug dosages; Drug resistance; Enrollments; Humans; Infections; Informed consent; Multicenter Studies as Topic; Multidrug-resistant; Pathogens; Phage; Phage Therapy; Phages; Pseudomonas aeruginosa; Pseudomonas aeruginosa infections; Quality of Life; Randomized Controlled Trials as Topic; Risk factors; Study Protocol; Testing
• ISSN: 1745-6215; 1745-6215
• DOI: 10.1186/s13063-022-07047-5

Bacteriophages (phages) are a promising anti-infective option for human disease. Major gaps remain in understanding their potential utility. This is a randomized, placebo-controlled, double-blind study of a single dose of intravenous phage in approximately 72 clinically stable adult cystic fibrosis volunteers recruited from up to 20 US sites with Pseudomonas aeruginosa airway colonization. The single dose of phage consists of a mixture of four anti-pseudomonal phages. Six sentinel participants will be sequentially enrolled with dose escalation of the phage mixture by one log beginning with 4 × 10 plaque-forming units in an unblinded stage 1. If no serious adverse events related to the study product are identified, the trial will proceed to a double-blinded stage 2. In stage 2a, 32 participants will be randomly assigned to one of three phage dosages or placebo in a 1:1:1:1 allocation. An interim analysis will be performed to determine the phage dosage with the most favorable safety and microbiological activity profile to inform phage dosing in stage 2b. During stage 2b, up to 32 additional volunteers will be randomized 1:1 to the phage or placebo arm. Primary outcomes include (1) the number of grade 2 or higher treatment-emergent adverse events, (2) change in log P. aeruginosa total colony counts in sputum, and (3) the probability of a randomly selected subject having a more favorable outcome ranking if assigned to receive phage therapy versus placebo. Exploratory outcomes include (1) sputum and serum phage pharmacokinetics, (2) the impact of phage on lung function, (3) the proportion of P. aeruginosa isolates susceptible to the phage mixture before and after study product administration, and (4) changes in quality of life. This trial will investigate the activity of phages in reducing P. aeruginosa colony counts and provide insights into the safety profile of phage therapy. ClinicalTrials.gov NCT05453578. Registered on 12 July 2022.