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

Not Applicable

Not yet recruiting

• Conditions: Klebsiella Pneumoniae Infection; E Coli Infections; Achromobacter; Cystic Fibrosis (CF); Stenotrophomonas Maltophilia Infection; Staphylococcus Aureus Infection

• Registration Number: NCT07048704
• Lead Sponsor: University of California, San Diego

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Status Verified: 2025-06
• Study First Submitted: 2025-06-24
• Study First Submitted QC: 2025-06-24
• Last Update Submitted: 2025-06-24
• Study First Posted: 2025-07-02
• Last Update Posted: 2025-07-02
• Study Start: 2025-10-01
• Primary Completion: 2026-12-31
• Study Completion: 2027-01-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1. Diagnosis of CF confirmed by CFTR genetics analysis or elevated sweat chloride

2. Age> 18yo at screening

3. Percent predicted FEV1 between 20 and 40% (GLI reference equations between 20 and 40%, or >40% in those who experience frequent pulmonary exacerbations or have severe disease indicators).

4. SpO2 of > 88% on pulse oximetry at rest after breathing room air for 20 minutes

5. Previous demonstrated ability to successfully complete home iv therapy with the selected antibiotic in the past 5 years. Waiver of this criteria is possible at the discretion of the investigators and made in conjunction with the primary caring physician.

6. Previous participation in a phage therapy trial is allowed if the inclusion and exclusion criteria are met and at the discretion of the investigators.

7. Availability of a phage cocktail that meet the following criteria:

   1. Demonstrate lytic activity against the subject's major bacterial pathogen
   2. Can be prepared according to FDA specifications at a titer of 1.0 x 10^9 pfu/dose for 14 doses.

Subject Exclusion Criteria

1. Untreated mycobacterial or fungal airway infection defined by professional guidelines

   a. Note: currently treated mycobacterial disease, airway fungal infection, or fungal prophylaxis therapy may be allowed at the discretion of the clinical investigators.

2. History of active C. difficile colitis infection. Patients with a history of C. difficile colitis must have had one negative stool test within 3 months of screening.

3. Presence of concerning exotoxin, virulence factors or antibiotic resistance genes in the pretreatment sequences of the major isolate or sputum metagenome at the discretion of the investigators.

4. Participants who are pregnant, planning to become pregnant during the study period, or breastfeeding.

5. Known allergy to any of treating materials

6. Any significant historical, clinical, laboratory, information that, in the opinion of the investigator, would make it unsafe for the subject to participate in this study

7. Participation in an interventional/therapeutic trial within 30 days of screening.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Safety and tolerability of combined IV antibiotic and bacteriophage therapy	From first dose (Day 1) through end of follow-up (Day 28 ± 5)	Safety will be assessed by the number, type, severity, and relatedness of adverse events (AEs), serious adverse events (SAEs), and events of special interest (ESIs) during and following the 7-day treatment period, in accordance with CTCAE criteria. Monitoring will occur from the initiation of study drug through the 28-day follow-up period.

Secondary Outcome Measures

Name	Time	Method
Microbiological activity of combined IV antibiotic and bacteriophage therapy	Baseline (Day -14 to Day 1) through Day 28 ± 5	Assessed by changes in bacterial burden in expectorated sputum samples, measured by quantitative culture (CFU/mL) and qPCR for the target pathogen. A response is defined as a ≥0.5 log reduction in bacterial load from baseline.