Bacteriophage Therapy in Patients With Urinary Tract Infections

Study Overview
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Brief Summary
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This is a phase I/II trial designed to evaluate bacteriophage therapy in patients with urinary tract infections.

Detailed Description
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This study will evaluate the safety and efficacy of bacteriophage therapy in patients with urinary tract infection (UTI). Patients to be enrolled will have urinary tract infections due to E. coli and K. pneumoniae. This will include asymptomatic patients with neurogenic bladder and symptomatic patients with complicated urinary tract infections who are at risk of UTI recurrence. Patients will be followed for bacterial clearance or recurrence of urinary tract infection.

Official Title
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A Phase I/II Study of Bacteriophage Therapy to Evaluate Safety, Tolerability, and Efficacy of Targeted Personalized Bacteriophage Treatments in Patients With Bacterial Infection of the Urinary Tract

Conditions
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Urinary Tract Infection Bacterial

Intervention / Treatment
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* Biological: Bacteriophage Therapy


Participation Criteria
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Eligibility Criteria
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General Inclusion Criteria: Males or females ≥18 years of age. Female patients of childbearing potential. Male patients must agree not to donate sperm up for one month. English-speaking. General Exclusion Criteria: Stage 4 or greater chronic kidney disease (CKD). Abnormal liver function tests >3×upper limit of normal (ULN). Other conditions which could confound study results. Body mass index of > 40 or weight less than 50 kg. Known allergy to phage products. Pregnant and/or breastfeeding. Immunocompromised. Need for antiviral medication. History of severe autonomic dysreflexia.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Initially, patients with neurogenic bladder and urinary tract infections will be enrolled and followed for bacterial eradication. Results from this cohort will be used to confirm or modify the phage dosing regimen before proceeding to the patients with symptomatic infection at risk of recurrence. The trial will use pre-specified criteria to determine what phage regimens should be evaluated.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intravenous (IV)<br>Phage administered via the intravenous route. | Biological: Bacteriophage Therapy<br>* Bacteriophage therapy will be personalized for each patient dependent on phage susceptibility testing<br>|
| Experimental: Intravesical (IVS)<br>Phage administered via the intravesical route. | Biological: Bacteriophage Therapy<br>* Bacteriophage therapy will be personalized for each patient dependent on phage susceptibility testing<br>|
| Experimental: Subcohort A<br>Selected phage for E. coli administered via selected route based on previous Arms. | Biological: Bacteriophage Therapy<br>* Bacteriophage therapy will be personalized for each patient dependent on phage susceptibility testing<br>|
| Experimental: Subcohort B<br>Selected phage for Klebsiella pneumoniae administered via selected route based on previous Arms. | Biological: Bacteriophage Therapy<br>* Bacteriophage therapy will be personalized for each patient dependent on phage susceptibility testing<br>|
| Experimental: Subcohort C<br>Selected phage for E. coli administered via selected route based on previous Arms. | Biological: Bacteriophage Therapy<br>* Bacteriophage therapy will be personalized for each patient dependent on phage susceptibility testing<br>|
| Experimental: Subcohort D<br>Selected phage for Klebsiella pneumoniae administered via selected route based on previous arms. | Biological: Bacteriophage Therapy<br>* Bacteriophage therapy will be personalized for each patient dependent on phage susceptibility testing<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identify ideal bacteriophage treatment regimens based on improvements in disease control rates | Microbiological eradication of target pathogen identified at baseline | baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the safety of bacteriophage therapy | Safety will be measured by the number and percent of treatment related adverse events. | At least 56 days | 
| Assess the tolerability of bacteriophage therapy | Tolerability will be measured by the percentage of patients who discontinue treatment due to adverse events | At least 56 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antimicrobial Resistance, Bacteriophage, Urinary Tract Infections, Phage