This is a Phase 1b study to assess the safety, tolerability, PK, and PD of investigational phage therapy (IP) in adults with SCI and bladder colonization (ASB). It is a single-center, randomized, double-blind, placebo-controlled study in adults with SCI with neurogenic bladders and bacteriuria who use indwelling catheters, or who require intermittent catheterization for bladder drainage.
Approximately 30 participants will be randomized 1:1 to receive either investigational phage therapy (3 x 10\^8 PFU phage(s)) or inert placebo (sterile normal saline solution) will be administered intravesicularly (instilled into the participant's bladder via catheter) twice a day (BID) for 7 days; the investigational phage therapies are personalized for each participant per phage susceptibility testing to the predominant E. coli pathogen in the participant's bladder. A mixture of up to three phages in a sterile solution will comprise the investigational phage therapy. The study duration for participants will be up to 65 days, which includes up to 30 days for screening, 7 days of IP treatment, and post-treatment assessments at Days 14, 21, 28 and 35 (7, 14, 21 and 28 days after the End of Treatment \[EOT\] on Day 7, respectively). Day 35 is defined as the EOS. The investigators will strive to enroll participants who are receiving inpatient care in the Spinal Cord Injury units, but enrollment of outpatients with SCI is also possible. Study enrollment will continue for up to 30 evaluable participants. The study will consist of a Screening Period of up to 30 days. On Day -1, eligible participants will be randomized to investigational phage therapy or placebo. The Treatment Period (Days 1-7) is 7 days and participants will receive a total of 14 doses of IP. The EOT will be after IP dose 14 on Day 7. The Follow-up Period is 35 days starting the day after the EOT with study assessments on Days 14, 21, and Day 35 (EOS). Adverse event data will be collected throughout the study from Treatment Day 1 through the EOS.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
30
A 20 mL sterile solution containing one to three individual phage drug substances (TPC) with total strength (potency) 3 x 10\^8 plaque-forming units (PFU), will be administered intravesicularly twice a day (one instillation in the morning and one in the evening \[at least six hours apart\], respectively) for 7 days. The selection of individual phages to include in the TPC are personalized/customized for each participant per phage susceptibility testing to the participant's urinary E. coli (testing is conducted by TAILФR Service Center). Each dose of TPC will be followed with a 10 mL flush of sterile 0.9% saline solution.
Sterile 0.9% saline solution also 20 mL, followed with a 10 mL flush of the same solution.
Michael E. DeBakey VA Medical Center
Houston, Texas, United States
RECRUITINGTo evaluate the safety and tolerability of phage therapy in adults ≥18 years of age with spinal cord injury (SCI) and bacteriuria with Escherichia coli (E. coli)
Safety and tolerability analysis of Adverse Events. The urinary symptom questionnaires provided by MedStar Health, USQNB will be used as a daily study diary. Participant's charts for AEs while they are hospitalized, and during study visits on days 14, 21, and 35 if they have been discharged before Day 14. Blood samples will be collected for chemistry and hematology on days 1, 3, 7, 14, 21, and 35. Urine samples will be collected to detect and analyze markers of inflammation on Days 1, 2, 3, 5, 7, 14, 21, and 35.
Time frame: 2 years
To evaluate the pharmacokinetics (PK) of investigational phage therapy
Blood samples will be collected to quantify phage titers, which will be measured as PFU (plaque-forming units) per mL (milliliter) of blood. To quantify phage titers, we will perform PCR to measure copies/volume of phage titer compared to a standard control of purified phage.
Time frame: 2 years
To evaluate of the pharmacodynamics (PD) of investigational phage therapy
Urine samples will be collected to analyze 1 log reduction in the urinary E. coli on Days 1, 2, 3, 5, 7, 14, 21, and 35. Analysis of recurrence of urinary E. coli colonization, incidence of urinary tract infection based on clinical signs and symptoms. Microbiological cure, defined as \<10\^3 CFU/mL of E. coli in the urine on Day 7.
Time frame: 2 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.