Department of Pediatrics, Johns Hopkins University School of Medicine, 200 North Wolfe Street, Room 3149, Baltimore, MD, 21287, USA.
Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.
Trials. 2022 Dec 28;23(1):1057. 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.
噬菌体（phages）是治疗人类疾病的一种很有前途的抗感染选择。但人们对其潜在用途仍存在很大的理解差距。
这是一项在约 72 名来自美国 20 个以上地点的临床稳定的成年囊性纤维化志愿者中进行的随机、安慰剂对照、双盲研究，这些志愿者均患有铜绿假单胞菌气道定植。单次静脉注射噬菌体剂量由四种抗假单胞菌噬菌体组成的混合物组成。前 6 名参与者将进行序贯入组，在非盲 1 期按一个对数级递增噬菌体混合物剂量，起始剂量为 4×10 噬菌斑形成单位。如果没有与研究产品相关的严重不良事件，则试验将进入双盲 2 期。在 2a 期，32 名参与者将以 1:1:1:1 的比例随机分配到三种噬菌体剂量或安慰剂组之一。将进行中期分析以确定具有最佳安全性和微生物学活性特征的噬菌体剂量，为 2b 期提供噬菌体剂量信息。在 2b 期，多达 32 名额外的志愿者将 1:1 随机分配到噬菌体或安慰剂组。主要结局包括（1）2 级或更高级别的治疗后不良事件数量，（2）痰中铜绿假单胞菌总菌落计数的对数变化，以及（3）随机选择的接受噬菌体治疗与安慰剂治疗的受试者如果分配到噬菌体治疗组，其结果排名更有利的概率。探索性结局包括（1）痰和血清噬菌体药代动力学，（2）噬菌体对肺功能的影响，（3）研究产品给药前后对噬菌体混合物敏感的铜绿假单胞菌分离株的比例，以及（4）生活质量的变化。
本试验将研究噬菌体减少铜绿假单胞菌菌落计数的活性，并深入了解噬菌体治疗的安全性概况。
ClinicalTrials.gov NCT05453578。于 2022 年 7 月 12 日注册。
