Bacteriophage Therapy in Spinal Cord Injury Patients With Bacteriuria

NCT06559618 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: H-54876 -202512122890593
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Bacteriuria; Spinal Cord Injuries; Asymptomatic Bacteriuria; Escherichia Coli

Keywords

Bacteriophage; Bacteriuria; Phage Therapy; Spinal Cord Injury; Intravesicular infusion; Neurogenic Bladder; Intermittent catheterization; Randomized clinical trial

Outcome Measures

Primary Outcomes (1)

• To 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.

  2 years

Secondary Outcomes (2)

• To evaluate the pharmacokinetics (PK) of investigational phage therapy

  2 years

• To evaluate of the pharmacodynamics (PD) of investigational phage therapy

  2 years

Other Outcomes (2)

• To explore the influence of phage therapy on the urinary tract microbiota

  2 years

• To explore the influence of phage therapy on the digestive tract microbiota

  2 years

Study Arms (2)

Phage Arm

EXPERIMENTAL

A sterile solution of one to three individual phages (cocktail) (3 x 10\^8 plaque forming units \[PFU\]) phage(s) will be administered intravesicularly (instilled into the participant's bladder via catheter) twice a day for 7 days. The name of the active treatment IP is TAILФR Phage Cocktail (TPC).

Drug: Phage Therapy

Placebo Arm

PLACEBO COMPARATOR

Sterile 0.9% saline solution will be instilled into the bladder via catheter twice a day for 7 days

Other: Placebo

Interventions

Placebo OTHER

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

Placebo Arm

Phage Therapy DRUG

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.

Also known as: Phage

Phage Arm

Eligibility Criteria

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

You may qualify if:

• Provision of signed and dated informed consent form.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Adult (\> age 18) with a diagnosis of Spinal Cord Injury/Disease (SCI/D) and neurogenic bladder. Eligible participants may include inpatients in the SCI care unit or outpatients receiving care at participating sites, regardless of the underlying cause of SCI (e.g., trauma, tumors or demyelinating).
• ASB with E. coli present in a quantity of ≥ 104 CFU/mL.
• Require an indwelling (transurethral or suprapubic) or intermittent catheterization for bladder drainage.
• 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.
• Participant will be hospitalized during the 7 days of treatment or will be willing to attend clinic visits either (a) daily for the 7 days of treatment, or (b) on Day 1 and Day 7 of dosing. On Day 1, the participant will receive in-person training on instillation of the IP into the bladder.

You may not qualify if:

• Unable to provide informed consent for themselves.
• Received a new antibiotic expected to kill the Gram-negative organisms in the urine between initial enrollment urine culture and the time of randomization.
• History of neutropenia, defined by ANC \< 1000 per µL within 6 months prior to screening.
• History of organ transplantation.
• Presence of a surgically modified bladder, except for a repaired ruptured bladder.
• HIV with a CD4 count \< 200 cells per µL.
• Unstable vital signs (e.g., fever, hypotension)
• Known urinary obstruction.
• Medical devices in the urinary tract (other than urinary catheters)
• Unless deemed acceptable by the sponsor-investigator, prescription drugs, OTC medications and supplements that acidify the urine are excluded.
• Stage 4 or greater chronic kidney disease
• Pregnant or breastfeeding female
• 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.
• 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.

Sponsors & Collaborators

• Barbara Trautner: lead

Study Sites (2)

Washington University in St Louis

St Louis, Missouri, 63110, United States

RECRUITING

Michael E. DeBakey VA Medical Center

Houston, Texas, 77030, United States

RECRUITING

Related Publications (4)

• Terwilliger A, Clark J, Karris M, Hernandez-Santos H, Green S, Aslam S, Maresso A. Phage Therapy Related Microbial Succession Associated with Successful Clinical Outcome for a Recurrent Urinary Tract Infection. Viruses. 2021 Oct 12;13(10):2049. doi: 10.3390/v13102049.

  PMID: 34696479 BACKGROUND

• Green SI, Kaelber JT, Ma L, Trautner BW, Ramig RF, Maresso AW. Bacteriophages from ExPEC Reservoirs Kill Pandemic Multidrug-Resistant Strains of Clonal Group ST131 in Animal Models of Bacteremia. Sci Rep. 2017 Apr 12;7:46151. doi: 10.1038/srep46151.

  PMID: 28401893 BACKGROUND

• Salazar KC, Ma L, Green SI, Zulk JJ, Trautner BW, Ramig RF, Clark JR, Terwilliger AL, Maresso AW. Antiviral Resistance and Phage Counter Adaptation to Antibiotic-Resistant Extraintestinal Pathogenic Escherichia coli. mBio. 2021 Apr 27;12(2):e00211-21. doi: 10.1128/mBio.00211-21.

  PMID: 33906920 BACKGROUND

• Green SI, Clark JR, Santos HH, Weesner KE, Salazar KC, Aslam S, Campbell JW, Doernberg SB, Blodget E, Morris MI, Suh GA, Obeid K, Silveira FP, Filippov AA, Whiteson KL, Trautner BW, Terwilliger AL, Maresso A. A Retrospective, Observational Study of 12 Cases of Expanded-Access Customized Phage Therapy: Production, Characteristics, and Clinical Outcomes. Clin Infect Dis. 2023 Oct 13;77(8):1079-1091. doi: 10.1093/cid/ciad335.

  PMID: 37279523 BACKGROUND

MeSH Terms

Conditions

Bacteriuria; Spinal Cord Injuries; Escherichia coli Infections; Urinary Bladder, Neurogenic

Interventions

Phage Therapy

Condition Hierarchy (Ancestors)

Urinary Tract Infections; Infections; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Neurologic Manifestations; Urinary Bladder Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Officials

• Barbara W Trautner, MD, PhD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Barbara W Trautner, MD, PhD

CONTACT

314 747 5258; trautner@wustl.edu

Rogelio Hernandez, MS

CONTACT

hrogelio@wustl.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind, placebo-controlled clinical trial
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: Phase 1b, single-center, randomized, double-blind, placebo-controlled study in adults with spinal cord injury with neurogenic bladders and bacteriuria who use indwelling catheters, or who require intermittent catheterization for bladder drainage

Study Record Dates

• First Submitted: July 21, 2024
• First Posted: August 19, 2024
• Study Start: February 3, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: May 5, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)