RECRUITINGPhase 1 / Phase 2INTERVENTIONAL

Phage Therapy for Recurrent UTIs in Kidney Transplant Recipients

Phase 1/ 2 Trial of Phage Therapy for Recurrent UTIs in Kidney Transplant Recipients

About This Trial

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.

Who May Be Eligible (Plain English)

Who May Qualify: 1. 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. 2. 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). 3. Ability to self-administer study drug (or a family member that will do so) and willing to adhere to the phage therapy regimen. 4. 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. 5. Provision of signed and dated willing to sign a consent form form 6. Stated willingness to comply with all study procedures and availability for the duration of the study. Who Should NOT Join This Trial: 1. Presents with hardware in the urinary tract (e.g. stent, percutaneous nephrostomy, chronic urinary catheter). 2. Recipient of \>1 kidney transplant. 3. Recipient of Ileal conduit. 4. Recipient of surgical neobladder. 5. Diagnosed with chronic urinary retention requiring self-catheterization. 6. Anatomic cause for rUTI such as ureteral stenosis. 7. Within the first 3 months of kidney transplant. 8. 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) 9. Diagnosed with active cytomegalovirus or BK virus infections. 10. Current pregnancy, actively trying to conceive, or lactating. 11. Known allergic reactions to phage products. ...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. 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. 2. 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). 3. Ability to self-administer study drug (or a family member that will do so) and willing to adhere to the phage therapy regimen. 4. 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. 5. Provision of signed and dated informed consent form 6. Stated willingness to comply with all study procedures and availability for the duration of the study. Exclusion Criteria: 1. Presents with hardware in the urinary tract (e.g. stent, percutaneous nephrostomy, chronic urinary catheter). 2. Recipient of \>1 kidney transplant. 3. Recipient of Ileal conduit. 4. Recipient of surgical neobladder. 5. Diagnosed with chronic urinary retention requiring self-catheterization. 6. Anatomic cause for rUTI such as ureteral stenosis. 7. Within the first 3 months of kidney transplant. 8. 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) 9. Diagnosed with active cytomegalovirus or BK virus infections. 10. Current pregnancy, actively trying to conceive, or lactating. 11. Known allergic reactions to phage products. 12. Prisoners or individuals without decisional capacity.

Treatments Being Tested

DRUG

phage therapy

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.

DRUG

control

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

Locations (1)

University of California, San Diego

La Jolla, California, United States