Evaluating TRL1068 for treating prosthetic joint infections

Phase 2 Study to Evaluate the Efficacy and Safety of TRL1068 for the Treatment of Chronic Prosthetic Joint Infection of the Knee or Hip Without Exchange Arthroplasty

This study is testing a new treatment called TRL1068 to see if it can help people with chronic infections in hip and knee joint replacements, making it easier to treat them without needing major surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years to 85 Years
• Sex: All
• Sponsor: Trellis Bioscience LLC (Industry-sponsored)
• Locations: 10 sites (Los Angeles, California and 9 other locations)
• Trial ID: NCT06621251 on ClinicalTrials.gov

What this trial studies

This Phase 2 study assesses the efficacy and safety of TRL1068, a human monoclonal antibody, in combination with a debridement, antibiotics, and implant retention (DAIR) procedure for chronic prosthetic joint infections (PJIs) of the hip and knee. The goal is to disrupt biofilm that protects pathogens, making them more susceptible to antibiotics, and potentially eliminate the need for the standard two-stage exchange surgery. Participants will be randomized to receive either TRL1068 with DAIR or standard care involving two-stage prosthetic joint replacement. The study aims to improve treatment outcomes for patients suffering from these difficult-to-treat infections.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 85 with chronic prosthetic joint infections of the hip or knee confirmed by bacterial culture.

Not a fit: Patients with fungal infections or those not willing to participate in randomization may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce the need for invasive surgeries and improve recovery times for patients with prosthetic joint infections.

How similar studies have performed: Previous studies have shown promise in targeting biofilms with similar approaches, but this specific treatment is novel.

Eligibility criteria

Inclusion Criteria:

1. Age 18 to 85 years, inclusive
2. Chronic PJI:

   1. Systemic Host Grade of A or B \[McPherson 2011\] (Appendix 3) and either
   2. First chronic PJI of the hip or knee, confirmed by synovial fluid aspirate culture or
   3. Recurrent chronic PJI of the hip or knee confirmed by synovial fluid aspirate culture
3. Willing to be randomized to either:

   1. Receive TRL1068 and to be scheduled for DAIR between Day 15 + 7 days (i.e., between days 15-22) and 10 weeks of targeted antibiotic treatment or
   2. Participate in an observational study arm that receives SoC (i.e., two-stage prosthetic joint replacement) and

   i. Sonication of the explanted prosthesis and performance of synovial fluid aspirates ii. Consents to conduct of stage 2 (implantation of new prosthesis)
4. At least 1 positive bacterial culture without concomitant fungal infection from the infected joint (a joint aspirate within 28 days prior to Screening is acceptable)
5. All identified pathogen(s) are susceptible to the planned antibiotic regimen
6. Availability of radiology assessments of the affected joint without signs of loosening of the prosthesis or presence of osteomyelitis
7. Willing and able to provide written informed consent
8. Willing to perform and comply with all study procedures, including attending clinic visits as scheduled
9. Men and women of childbearing potential (WOCBP) must be willing to practice a highly effective method of contraception that may include, but is not limited to, abstinence, sex only with persons of the same sex, monogamous relationship with vasectomized partner, vasectomy, hysterectomy, bilateral tubal ligation, licensed hormonal methods, intrauterine device (IUD), or use of spermicide combined with a barrier method (e.g., condom, diaphragm) through Day 365.

Exclusion Criteria:

1. PJI associated with presence of concomitant fungal infection or bacterial pathogens that, even when in planktonic form (i.e., when released from biofilm), cannot be adequately treated with available antibiotics.
2. More than one draining sinus and single draining sinus of \> 1 cm
3. Less than 3 years life expectancy based on underlying morbidities
4. Expected to receive chronic suppressive antibiotic therapy
5. Congestive heart failure; New York Heart Association (NYHA) Functional Classification of Heart Failure Grade \> 3B
6. Uncontrolled diabetes, defined as hemoglobin A1c \> 7.4%.
7. BMI \> 45
8. Any acute illness within 14 days of Day 1 that could confound the evaluation of safety evaluation of TRL1068, especially local or systemic fungal and other known or suspected bacterial infections
9. Receiving or recently received another investigational drug (within 30 days of Day 1, or 5 half-lives of the investigational drug, whichever is longer)
10. Received any vaccine within 14 days prior to Day 1
11. Positive serum pregnancy test for WOCBP, or nursing women
12. History of drug or alcohol abuse that, in the opinion of the Investigator, would interfere with the patient's ability to comply with all study requirements
13. Any other comorbidity or condition that, in the opinion of the Investigator would make the patient unsuitable for the study or unable to comply with the study requirements.

Where this trial is running

Los Angeles, California and 9 other locations

• UCLA — Los Angeles, California, United States (Not_yet_recruiting)
• Gulfcoast Research Institute — Sarasota, Florida, United States (Not_yet_recruiting)
• Phoenix Clinical Research — Tamarac, Florida, United States (Recruiting)
• Sinai Hospital Baltimore — Baltimore, Maryland, United States (Recruiting)
• NYU Langone Health — New York, New York, United States (Recruiting)
• University of Rochester — Rochester, New York, United States (Not_yet_recruiting)
• M3 Wake Research Associates — Wilmington, North Carolina, United States (Recruiting)
• University of Texas Medical Branch at Galveston — Galveston, Texas, United States (Not_yet_recruiting)
• Houston Methodist — Houston, Texas, United States (Not_yet_recruiting)
• University of Utah — Salt Lake City, Utah, United States (Not_yet_recruiting)

Study contacts

• Study coordinator: Anton Leighton, MD

Conditions Prosthetic Joint Infections of Hip; Prosthetic Joint Infections of Knee; biofilm; antibiotic-resistant infections