Safety of Combined Intravenous Antibiotic and Bacteriophage Therapy in Adults With Cystic Fibrosis and Antibiotic-Resistant Lung Infections

Официальное название

Taking Advantage of Phage Technologies (TAPT) to Facilitate Phage Therapy While Reducing the Use of Antibiotics in the Management of Cystic Fibrosis (CF)

Обзор

This is a Phase 1, open-label, multi-center pilot study evaluating the safety and microbiological activity of intravenous (IV) bacteriophage therapy in combination with standard IV antibiotics in adults with cystic fibrosis (CF) experiencing pulmonary exacerbations due to antibiotic-resistant bacterial infections. Eligible participants will receive a 7-day course of IV antibiotics, selected by their treating clinician, along with a phage cocktail specifically formulated to target their identified bacterial pathogen (Pseudomonas aeruginosa, Klebsiella spp., Stenotrophomonas maltophilia, Escherichia coli, Staphylococcus aureus, or Achromobacter xylosoxidans). The primary objective is to assess the safety and tolerability of this combined treatment approach. Secondary and exploratory outcomes include assessment of changes in sputum bacterial burden, lung function (spirometry and oscillometry), quality of life, and bacteriophage pharmacokinetics. Results from this study will inform the feasibility and design of future clinical trials using phage therapy in the CF population.

Подробное описание

Cystic fibrosis (CF) is a genetic disease characterized by chronic and recurrent pulmonary infections, often caused by antibiotic-resistant bacteria. These infections contribute significantly to lung function decline, reduced quality of life, and early mortality. Given the rising prevalence of antimicrobial resistance (AMR) and limited efficacy of conventional antibiotic therapies, there is an urgent need for novel therapeutic strategies. Bacteriophage (phage) therapy-using viruses that infect and lyse specific bacteria-has emerged as a promising, targeted approach for managing drug-resistant bacterial infections.

This is a Phase 1, open-label, multi-center pilot study designed to assess the safety, tolerability, and preliminary biological activity of intravenous (IV) bacteriophage therapy administered in combination with standard IV antibiotics in adults with CF experiencing a pulmonary exacerbation caused by antibiotic-resistant bacterial pathogens. Participants must have a confirmed diagnosis of CF and recent culture-proven infection with one of six target bacteria: Pseudomonas aeruginosa, Klebsiella spp., Stenotrophomonas maltophilia, Escherichia coli, Staphylococcus aureus, or Achromobacter xylosoxidans.

The study will enroll up to 30 participants across three U.S. clinical sites. Eligible subjects will receive a 7-day course of IV antibiotics prescribed by their clinical team, along with a pathogen-specific four-phage cocktail administered twice daily through a peripherally inserted central catheter (PICC). The phage cocktails are prepared under GMP conditions and have demonstrated lytic activity against clinical isolates of each target pathogen.

The primary endpoint is to evaluate the safety and tolerability of the combined phage-antibiotic therapy by monitoring adverse events (AEs), serious adverse events (SAEs), and events of special interest (ESIs). Secondary endpoints include changes in bacterial load in sputum (colony counts and qPCR), changes in lung function (spirometry and oscillometry), and patient-reported quality of life measures. An exploratory endpoint includes characterizing the pharmacokinetic profile of IV phage therapy in serum and sputum.

Initial doses of phage will be administered under direct clinical observation to monitor for immediate reactions. If well-tolerated, subsequent doses may be self-administered at home. Follow-up assessments will be conducted up to 28 days post-treatment, with additional safety monitoring extending up to 217 days. The trial is not designed to support regulatory approval but to generate essential safety and feasibility data to guide future efficacy trials in this high-need patient population.

Вмешательства

• Препарат Intravenous Bacteriophage Cocktail plus Standard IV Antibiotics
  Participants will receive a seven-day course of intravenous (IV) bacteriophage therapy in combination with standard IV antibiotics. The bacteriophage therapy consists of a pathogen-specific cocktail containing four purified, lytic bacteriophages selected based on pre-treatment sensitivity testing of the participant's bacterial isolate. Each phage cocktail targets one of the following antibiotic-resistant pathogens: Pseudomonas aeruginosa, Klebsiella spp., Stenotrophomonas maltophilia, Escherichi

Первичные конечные точки

• Safety and tolerability of combined IV antibiotic and bacteriophage therapy assessed by the number, type, severity, and relatedness of adverse events (AEs), serious adverse events (SAEs), and events of special interest (ESIs) [Срок оценки: Baseline (Day -14 to Day 1) through Day 28 ± 5]

Вторичные конечные точки (4)

• Microbiological activity of combined IV antibiotic and bacteriophage therapy [Срок оценки: Baseline (Day -14 to Day 1) through Day 28 ± 5]
• Microbiological Response: Sputum Bacterial Load (Quantitative Culture) measured by quantitative culture [Срок оценки: From the first dose through 28 days after the last dose of study treatment]
• Change in Lung Function (FEV₁ Percent Predicted) measured by percent predicted forced expiratory volume in one second (FEV₁ % predicted). [Срок оценки: Baseline to Day 36]
• Change in Respiratory Symptoms Using the Cystic Fibrosis Respiratory Symptom Diary - Chronic Respiratory Infection Symptom Score (Cystic Fibrosis Respiratory Symptom Diary-CRISS) [Срок оценки: Baseline to Day 36]

Критерии участия

Критерии включения

• Age ≥ 18 years.
• Confirmed diagnosis of cystic fibrosis.
• Sputum culture within 24 months and at screening showing at least one of the following: Pseudomonas aeruginosa, Klebsiella spp., Stenotrophomonas maltophilia, Escherichia coli, Staphylococcus aureus, or Achromobacter xylosoxidans.
• Percent predicted FEV₁ ≥ 40% (GLI).
• If ppFEV₁ > 40%, must have ≥ 1 pulmonary exacerbation per year requiring IV antibiotics or radiographic evidence of severe disease.
• Prior successful home IV antibiotic therapy within 5 years (may be waived by investigator).
• Available phage cocktail with lytic activity against the participant's pathogen.

Oxygen saturation > 88% on room air after rest. Able to provide written informed consent.

Критерии исключения

• Untreated or uncontrolled mycobacterial or fungal airway infection.
• History of Clostridioides difficile without a negative test within 3 months. Concerning exotoxin, virulence, or resistance genes in the bacterial isolate (per investigator).
• Mixed-species bacterial infection at screening.
• Participation in another interventional trial within 30 days.
• Allergy or hypersensitivity to study materials.
• Pregnancy, planned pregnancy, or breastfeeding.
• Any condition or abnormality that, in the investigator's judgment, makes participation unsafe or may interfere with study assessments.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07280598 · 812895 · 314645-00001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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