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

NCT07280598 | Not Yet Recruiting Phase 1 FDA Drug

• 2 other identifiers: 812895314645-00001
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

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.

Conditions

CF - Cystic Fibrosis; Klebsiella Pneumoniae Infection; E Coli Infections; Staphylococcus Aureus Infection; Achromobacter; Stenotrophomonas Maltophilia Infection

Keywords

cystic fibrosis; CF; Phage; bacteriophage

Outcome Measures

Primary Outcomes (1)

• 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)

  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 the study drug through the 28-day follow-up period.

  Baseline (Day -14 to Day 1) through Day 28 ± 5

Secondary Outcomes (4)

• Microbiological activity of combined IV antibiotic and bacteriophage therapy

  Baseline (Day -14 to Day 1) through Day 28 ± 5

• Microbiological Response: Sputum Bacterial Load (Quantitative Culture) measured by quantitative culture

  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).

  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)

  Baseline to Day 36

Study Arms (1)

Phase 1 Study of Combined IV Antibiotics and Bacteriophage Therapy for Antibiotic-Res

EXPERIMENTAL

This arm will evaluate the safety and microbiological activity of a combined intravenous (IV) antibiotic and bacteriophage therapy in adults with cystic fibrosis (CF) who are experiencing pulmonary exacerbations caused by antibiotic-resistant bacterial pathogens. Participants will receive a clinician-selected, standard IV antibiotic regimen for 7 days, administered twice daily. In parallel, participants will receive a matched, pathogen-specific bacteriophage cocktail via IV infusion, also administered twice daily for 7 days. The phage cocktails consist of four lytic bacteriophages targeting one of the following pathogens: Pseudomonas aeruginosa, Klebsiella spp., Stenotrophomonas maltophilia, Escherichia coli, Staphylococcus aureus, or Achromobacter xylosoxidans. The first three phage doses will be administered in a monitored clinic setting; remaining doses will be self-administered at home via PICC line. This is a Phase 1, open-label, multi-site pilot study focused on safety.

Drug: Intravenous Bacteriophage Cocktail plus Standard IV Antibiotics

Interventions

Intravenous Bacteriophage Cocktail plus Standard IV Antibiotics DRUG

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, Escherichia coli, Staphylococcus aureus, or Achromobacter xylosoxidans. Phage cocktails are administered IV twice daily at a concentration of 1x10⁹ PFU/mL, following antibiotic infusion. The first three doses are observed in clinic; remaining doses are self-administered at home via PICC line. All phages are produced under GMP conditions and screened to be lytic-only, free of known toxin, resistance, or lysogeny genes.

Phase 1 Study of Combined IV Antibiotics and Bacteriophage Therapy for Antibiotic-Res

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of California, San Diego: lead

MeSH Terms

Conditions

Cystic Fibrosis; Escherichia coli Infections; Staphylococcal Infections

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Gram-Positive Bacterial Infections

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of the Clinical Molecular Microbiology Laboratory

Study Record Dates

• First Submitted: November 20, 2025
• First Posted: December 12, 2025
• Study Start: December 31, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): January 30, 2027
• Last Updated: December 12, 2025

Record last verified: 2025-12