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RECRUITINGPhase 1INTERVENTIONAL

Bacteriophage Therapy in Spinal Cord Injury Patients With Bacteriuria

A Phase 1B Study to Assess Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Bacteriophage Therapy in Spinal Cord Injury Patients With Bacteriuria

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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.

Who May Be Eligible (Plain English)

Who May Qualify: 1. Provision of signed and dated willing to sign a consent form form. 2. Stated willingness to comply with all study procedures and availability for the duration of the study. 3. Adult (\> age 18) inpatients in the SCI care units with neurogenic bladders or outpatients in the SCI care clinics. 4. ASB with E. coli present in a quantity of ≥ 104 CFU/mL). 5. Require an indwelling (transurethral or suprapubic) or intermittent catheterization for bladder drainage. 6. Women of childbearing potential and men with female partners of childbearing potential must use two forms of effective contraception during the study and for two weeks afterwards. 7. Participant will be hospitalized during the 7 days of treatment or will be willing to come into clinic to receive the first dose of IP and training (of participant and/or caregiver) on how to instill the IP into the bladder. Who Should NOT Join This Trial: 1. Unable to provide willing to sign a consent form for themselves. 2. Received a new antibiotic expected to kill the Gram-negative organisms in the urine between initial enrollment urine culture and the time of randomization. 3. History of neutropenia, defined by ANC \< 1000 per µL within 6 months prior to screening. 4. History of organ transplantation. 5. Presence of a surgically-modified bladder, except for a repaired ruptured bladder. 6. HIV with a CD4 count \< 200 cells per µL. 7. Unstable vital signs (e.g., fever, hypotension) ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: 1. Provision of signed and dated informed consent form. 2. Stated willingness to comply with all study procedures and availability for the duration of the study. 3. Adult (\> age 18) inpatients in the SCI care units with neurogenic bladders or outpatients in the SCI care clinics. 4. ASB with E. coli present in a quantity of ≥ 104 CFU/mL). 5. Require an indwelling (transurethral or suprapubic) or intermittent catheterization for bladder drainage. 6. Women of childbearing potential and men with female partners of childbearing potential must use two forms of effective contraception during the study and for two weeks afterwards. 7. Participant will be hospitalized during the 7 days of treatment or will be willing to come into clinic to receive the first dose of IP and training (of participant and/or caregiver) on how to instill the IP into the bladder. Exclusion Criteria: 1. Unable to provide informed consent for themselves. 2. Received a new antibiotic expected to kill the Gram-negative organisms in the urine between initial enrollment urine culture and the time of randomization. 3. History of neutropenia, defined by ANC \< 1000 per µL within 6 months prior to screening. 4. History of organ transplantation. 5. Presence of a surgically-modified bladder, except for a repaired ruptured bladder. 6. HIV with a CD4 count \< 200 cells per µL. 7. Unstable vital signs (e.g., fever, hypotension) 8. Symptoms of active urinary tract infection defined as fever, autonomic dysreflexia, generalized increase in spasticity, bladder spasms, new sweating, increase or change in lower abdominal pain, increase in burning or pain when passing urine, increase in burning or pain during catheterization, blood in the urine, or an increased sensation of urinary urgency (MedStar Health, Urinary Symptom Questionnaires for Neurogenic Bladder \[USQNB\]) (Section 11.2). The presence of any one of these symptoms, unless explained by a non-urinary or non-infectious condition, will be an exclusion criterion. 9. Known urinary obstruction. 10. Medical devices in the urinary tract (other than urinary catheters) 11. Unless deemed acceptable by the sponsor-investigator, prescription drugs, OTC medications and supplements that acidify the urine are excluded. 12. Stage 4 or greater chronic kidney disease 13. Pregnant or breastfeeding female 14. Three or more episodes of autonomic dysreflexia in prior 30 days; defined as those patients who have a SCI and who have had a documented sudden increase in systolic blood pressure of greater than 40 mmHg due to an irritation or stimulation (including bladder or bowel irritation) below the level of the SCI. Autonomic dysreflexia can include findings of hypertensive crisis or emergency, clinically significant bradycardia/tachycardia, severe headache or other severe reaction requiring an acute intervention. The sponsor-investigator will evaluate if a history of severe autonomic dysreflexia is suspected but not clearly identified. 15. In the opinion of the sponsor-investigator, medical or psychiatric illness that would interfere with participation such as active, severe, progressive, or uncontrolled hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, or neurologic disease.

Treatments Being Tested

DRUG

Phage Therapy

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.

OTHER

Placebo

Sterile 0.9% saline solution also 20 mL, followed with a 10 mL flush of the same solution.

Locations (1)

Michael E. DeBakey VA Medical Center
Houston, Texas, United States