Phage Therapy for Recurrent UTIs in Kidney Transplant Recipients

NCT06409819 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 809673
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This proposal will take an important first step in the study of phage therapy for treatment of recurrent urinary tract infection (rUTI) in female kidney transplant recipients (KTR); a common condition that is associated with increasing multidrug resistance, sickness, loss of kidney function and death. The investigators will conduct a randomized phase I/II pilot clinical trial of targeted phage therapy versus placebo in asymptomatic female KTR with a history of rUTI due to Escherichia coli to assess safety, tolerability, and feasibility of this approach, possible efficacy, and changes in the gut and urinary microbiome during the 180 days of the study. This highly innovative and impactful proposal will provide proof of concept data and also inform the design of a subsequent larger phase III clinical trial of phage therapy for rUTI treatment in KTR and will have broad downstream effects within the fields of infectious diseases and transplantation.

Conditions

Urinary Tract Infection, Recurrent

Outcome Measures

Primary Outcomes (4)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  Safety of phage administration will be assessed by the incidence of adverse events (AE) as assessed by CTCAE v4.0. As this is a phase 1/ 2 pilot clinical study, the primary outcome is safety and tolerability of the IP.

  180 days

• Enrollment Feasibility

  Enrollment feasibility of the trial protocol will be assessed by enrollment and randomization (goal is ≥75% of target N at year 1 of the award).

  180 days

• Proportion of participants with a phage match

  Proportion of participants with a phage match will be assessed by the number of enrolled participants with a phage match (goal is ≥70%).

  180 days

• Study Drug Adherence

  Adherence to study drug administration by the participants (goal is ≥90%),

  180 days

Secondary Outcomes (9)

• Treatment Efficacy

  180 days

• Desirability of Outcome Rankings (DOOR) Score

  180 days

• Proportion of Participants with UTI

  180 days

• Days to first symptomatic UTI from the original infecting pathogen

  180 days

• Microbiological Eradication of Asymptomatic Bacteriuria

  180 days

Study Arms (2)

Intervention phage therapy

ACTIVE COMPARATOR

Clear 1 milliliter (ml) solution in a plastic needless syringe. Phage therapy will consist of twice daily intravenous (IV) dose of previously selected phage combination of at least 109 plaque forming units (PFU)/ ml concentration per phage but not to exceed 5EU/Kg/hr of total lipopolysaccharide endotoxin for the entire dose as per FDA guidelines.

Drug: phage therapy

Intervention control arm (normal saline placebo)

PLACEBO COMPARATOR

Clear 1mL solution in a plastic needless syringe. Placebo will consist of IV normal saline administered in the same manner as the active comparator for 7 days.

Drug: control

Interventions

phage therapy DRUG

phage therapy will consist of a combination of three lytic phages that are active against the participant's E. coli isolates and will be administered intravenously twice daily for 7 days.

Also known as: targeted phage therapy

Intervention phage therapy

control DRUG

Participants assigned to the control arm will start a 7-day course of intravenous sterile normal saline (placebo) administered twice daily.

Also known as: placebo

Intervention control arm (normal saline placebo)

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Adult cis-gender female kidney transplant recipients (KTRs) aged \>18 years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female kidney transplant recipients, aged 18 and older with a confirmed diagnosis of a history of recurring UTI with E. coli as their typical uropathogen.
• Two urine culture proven UTIs in prior 6 months or three in prior 12 months due to E coli. UTI is defined as any change in symptoms from baseline urinary comfort (dysuria, hematuria, abdominal/flank pain, increased urinary frequency) or systemic signs of infection (fever, chills, systemic inflammatory reaction syndrome etc.) associated with a positive urine culture with bacterial growth of ≥104 colony forming units/mL).
• Ability to self-administer study drug (or a family member that will do so) and willing to adhere to the phage therapy regimen.
• For participants able to become pregnant: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 6 months after the end of phage therapy administration.
• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study.

You may not qualify if:

• Presents with hardware in the urinary tract (e.g. stent, percutaneous nephrostomy, chronic urinary catheter).
• Recipient of \>1 kidney transplant.
• Recipient of Ileal conduit.
• Recipient of surgical neobladder.
• Diagnosed with chronic urinary retention requiring self-catheterization.
• Anatomic cause for rUTI such as ureteral stenosis.
• Within the first 3 months of kidney transplant.
• Venous access sites or in whom an existing venous access site needs to be preserved for future need (as per the participant's transplant nephrologist/ surgeon)
• Diagnosed with active cytomegalovirus or BK virus infections.
• Current pregnancy, actively trying to conceive, or lactating.
• Known allergic reactions to phage products.
• Prisoners or individuals without decisional capacity.

Sponsors & Collaborators

• University of California, San Diego: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

University of California, San Diego

La Jolla, California, 92037, United States

RECRUITING

MeSH Terms

Conditions

Urinary Tract Infections

Interventions

Phage Therapy

Condition Hierarchy (Ancestors)

Infections; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Central Study Contacts

Saima Aslam, M.D.

CONTACT

(619) 543-3108; rUTIphagestudy@health.ucsd.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Both the phage preparation and placebo will be packaged as 1 ml clear solution in a plastic syringe. For safety, the pharmacy and research team will be aware of the assigned intervention. Only the participants will be blinded to study arm assignment. The effectiveness of the blinding process will be assessed by querying participants which intervention they think they received after the final participant has completed the 180-day study period by assessing the level of agreement between self-report and actual assignment. Study intervention will only be initiated while the participant is asymptomatic and does not have an active symptomatic UTI. Eligible participants will be randomized to phage therapy or placebo in a 2:1 fashion.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Model Details: Eligible participants will be randomized to phage therapy or placebo in a 2:1 fashion. Participants will be blinded to study assignment.

Study Record Dates

• First Submitted: April 23, 2024
• First Posted: May 10, 2024
• Study Start: June 15, 2025
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): March 1, 2027
• Last Updated: August 14, 2025

Record last verified: 2025-08

Locations

US (1)