Phage Therapy for Recurrent UTIs in Kidney Transplant Recipients

NCT ID: NCT06409819

Last Updated: 2025-08-14

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-06-15
• Study Completion Date: 2027-03-01

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.

Detailed Description

The overarching hypothesis is that phage therapy directed against E. coli in female KTR is safe and associated with a reduction in UTI event rate via a targeted impact on the gut and urinary microbiome. This is a Phase 1/ 2 randomized, placebo-controlled clinical trial.

• A description of methods to be used to minimize bias Participants will be randomized to one of 2 arms - one active intervention phage therapy and the second is active intervention control arm (normal saline placebo). Participants will not be aware of study assignment and the medication delivered to them will look identical - clear 1mL solution in a plastic needless syringe.
• The number of study groups/arms and study intervention duration:

• Investigators plan to enroll participants that fulfill eligibility criteria until they reach their goal of 16 participants in each arm (total N= 32).

This clinical trial will evaluate the effect of phage only (without concomitant antibiotics) compared to placebo for UTI prevention in asymptomatic female KTR with a history of rUTI. There are no rigorous, published trials testing this approach, nor are there new therapeutics for rUTI in KTR on-market at this time. Most IND cases or trials compare phage plus antibiotic which limits the ability to isolate the contribution from phage to treatment success. The proposed research will utilize a phase I/II pilot trial designed to assess the safety, tolerability, and feasibility of therapy, compare potential efficacy, and assess changes to microbiome profiles in the female participants who will receive either phage or placebo. As the participants will be treated when they are asymptomatic, no active control is needed and so Investigators will use normal saline placebo.

Conditions

Urinary Tract Infection, Recurrent

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

Intervention phage therapy

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.

Group Type: ACTIVE_COMPARATOR

phage therapy

Intervention Type: 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.

Intervention control arm (normal saline placebo)

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.

Group Type: PLACEBO_COMPARATOR

control

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: DRUG

control

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

Intervention Type: DRUG

Other Intervention Names

targeted phage therapy; placebo

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

University of California, San Diego

OTHER

Sponsor Role: lead

Responsible Party

Saima Aslam

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of California, San Diego

La Jolla, California, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Saima Aslam, M.D.

Role: CONTACT

rUTIphagestudy@health.ucsd.edu

(619) 543-3108

Facility Contacts

Saima Aslam, MD

Role: primary

saslam@health.ucsd.edu

8586577643

Other Identifiers

809673

Identifier Type: -

Identifier Source: org_study_id