Use of Phage Therapy for Treatment of a Periprosthetic Joint Infection

NCT ID: NCT06827041

Last Updated: 2025-02-14

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-02-22
• Study Completion Date: 2025-02-28

Brief Summary

The goal of this clinical trial is to learn about the safety, tolerability and activity or efficacy of systemic intravenous and intraarticular administration of a mono-bacteriophage (phage) peparation in a patient with chronic-recalcitrant methicillin-resistant Staphylococcus epidermidis (MRSE) periprosthetic joint infection (PJI) and also to understand clinical changes pre- and post-therapy, as well as identifying adjunctive changes in biomarkers (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], and interleukin-6 [IL-6]) correlated with PJI.

Phage will be administered to the study participant with chronic PJI twice daily over a total duration of two weeks via two routes: a) intravenous (through vein) and b) intra-articular (through the affected joint). Phage therapy is given 4 hours after the patient receives their standard of care antibiotic therapy. The patient will remain in clinical follow-up for up to a year.1

Detailed Description

At The Ottawa Hospital (TOH), the orthopedic infectious diseases team is currently managing a very challenging case: a 78-year-old female with a severe, chronic-recalcitrant right hip PJI due to a multidrug resistant strain of S. epidermidis in which surgical source control with complete removal of implants cannot be achieved, and in whom there are no viable antibiotic treatment options for chronic suppressive therapy. This patient has undergone multiple surgical revisions with complex reconstructions and adjunctive flap coverage procedures and has received prolonged courses of antibiotic therapy. Unfortunately, this patient suffered multiple, severe antibiotic allergic reactions during initial treatment course which has precluded the use of any viable suppressive therapy - a treatment strategy which is critical to preventing relapse of infection and is at the crux of chronic PJI management.

In the absence of any viable adjunctive antimicrobial therapy, this patient is at very high risk of mortality. The Investigators have exhausted all surgical and medical management of PJI for our patient. Remaining on lower dose daptomycin and adjunctive oral rifampin, the patient continued to experience myalgias and neuropathy. It was anticipated that with eventual discontinuation of daptomycin (this patient cannot remain indefinitely on this therapy given her symptoms), her infection would again rapidly relapse with systemic symptoms. This infection is associated with a high risk of mortality without a viable suppressive antimicrobial treatment; a more aggressive surgical approach (high right leg amputation and hemipelvectomy) to reduce the burden of infection is not possible in this patient given her frailty, co-morbidity, resultant significant physical debility and risk of surgical complications. Given the above, phage therapy poses very low risk and is a remaining possible medical therapy that may eradicate her infection.

The primary objective of this study is to investigate the safety, tolerability and activity or efficacy of systemic (intravenous) and intra-articular administration of phage in our patient with chronic-recalcitrant methicillin-resistant S. epidermidis PJI.

Secondary objectives will be documenting clinical changes pre- and post-therapy, as well as identifying adjunctive changes in biomarkers (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], and interleukin-6 [IL-6]) correlated with PJI.

In this study, lytic phage prepared in injection-grade saline will be administered to the patient both intravenously and intraarticularly, twice a day for a duration of 14 days. In addition to phage therapy, the patient will receive standard of care antibiotic therapy.

The patient will remain in clinical follow-up for up to one year.

Conditions

Periprosthetic Joint Infection

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phage therapy

Lytic monophage prepared in injection-grade saline will be given via two routes: a) intravenously twice daily, and concomitantly, b) intra-articularly twice daily, for a total duration of 14 days. In addition to phage therapy, the patient will receive standard of care antibiotic therapy.

Group Type: EXPERIMENTAL

Phage (Cytophage Technologies)

Intervention Type: BIOLOGICAL

Our phage is a new type of investigational treatment for bacterial infections. Our lytic, monophage preparation was provided by Cytophage Technologies and underwent rigorous testing to ensure final product potency (7 x 10^9 PFU/dose), purity, fidelity, and safety; laboratory tests demonstrate phage in vitro efficacy against the S. epidermidis strain.

Phage prepared in injection-grade saline will be given via two routes: a) intravenously twice daily, and concomitantly, b) intraarticularly twice daily, for a total duration of 14 days.

Interventions

Phage (Cytophage Technologies)

Our phage is a new type of investigational treatment for bacterial infections. Our lytic, monophage preparation was provided by Cytophage Technologies and underwent rigorous testing to ensure final product potency (7 x 10^9 PFU/dose), purity, fidelity, and safety; laboratory tests demonstrate phage in vitro efficacy against the S. epidermidis strain.

Phage prepared in injection-grade saline will be given via two routes: a) intravenously twice daily, and concomitantly, b) intraarticularly twice daily, for a total duration of 14 days.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

This N-of-1 Phage therapy is designed for one patient who meet the following conditions.

• willingness to provide signed and dated informed consent form to participate in the clinical study.
• severe chronic periprosthetic joint infection due to a multidrug resistant strain of S. epidermidis in which surgical source control with complete removal of implants cannot be safely achieved
• have received multiple surgical revisions with complex reconstructions and adjunctive flap coverage procedures and prolonged courses of antibiotic therapy and suffered multiple, severe antibiotic allergic reactions during initial treatment course which has lead to the use of any viable suppressive therapy impossible
• complex burden of hardware
• poor bone quality and hip instability with high associated morbidity and mortality due to the S. epidermidis infection

Exclusion Criteria

• below age 18 years

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

Sponsors

Cytophage Technologies Inc.

UNKNOWN

Sponsor Role: collaborator

Ottawa Hospital Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Marisa Azad

Assistant Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Marisa A Azad, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Ottawa Hospital Research Institute

Locations

Ottawa Hospital Research Institute

Ottawa, Ontario, Canada

Countries

Canada

Other Identifiers

20231130

Identifier Type: -

Identifier Source: org_study_id