TRL1068 for Prosthetic Joint Infection

Recruiting at 16 trial locations

Overseen By Adriane Kisch-Hancock

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Trellis Bioscience LLC

Must not be taking: Chronic suppressive antibiotics

Disqualifiers: Fungal infection, Heart failure, Uncontrolled diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 369

Duration: 6 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called TRL1068, designed to assist people with chronic infections in hip or knee replacements. The treatment aims to make bacteria more susceptible to antibiotics, allowing patients to retain their original joint implants instead of undergoing major replacement surgery. Participants must have a confirmed bacterial infection in their hip or knee joint and be open to trying a new procedure combined with antibiotics. This trial may suit those struggling with ongoing joint infections and seeking alternatives to extensive surgery. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group, offering a promising alternative to surgery.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants should not be on chronic suppressive antibiotic therapy and should not have received another investigational drug recently. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that TRL1068 in combination with DAIR is likely to be safe?

Research has shown that TRL1068 might be a safe option for treating infections in artificial joints. In an earlier study, researchers administered TRL1068 to individuals with long-term knee or hip infections. The treatment was generally well-tolerated, with mild side effects such as headaches and nausea. These side effects were not serious and resolved quickly. The study found no major safety issues, suggesting that TRL1068 is a promising safe treatment option for those facing these challenging joint infections. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for prosthetic joint infections (PJIs) involve a lengthy two-stage surgery process. However, TRL1068 offers a potentially game-changing approach by combining a drug with a DAIR (Debridement, Antibiotics, and Implant Retention) procedure. Administered intravenously, TRL1068 targets bacteria in a novel way, potentially reducing the need for extensive surgeries. Researchers are excited because this approach may significantly cut down recovery time and improve outcomes for patients suffering from PJIs.

What evidence suggests that TRL1068 might be an effective treatment for prosthetic joint infection?

Research has shown that TRL1068 can break down the protective layers, called biofilms, that bacteria create, which make it difficult for antibiotics to work. In this trial, participants in the experimental arm will receive TRL1068 alongside a DAIR procedure. In earlier studies, patients with deep joint infections treated with TRL1068 had their infections completely cleared without needing to replace their original joint implants. This suggests that TRL1068 can enhance antibiotic effectiveness, possibly reducing the need for more invasive surgeries. Overall, TRL1068 appears promising in treating long-lasting joint infections by boosting the effectiveness of current antibiotic treatments. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-85 with a first or recurrent chronic prosthetic joint infection in the knee or hip, confirmed by culture. Participants must have stable implants without osteomyelitis and be able to consent and comply with study procedures, including follow-up visits.

Inclusion Criteria

My overall health is rated as good or fair.

I have a first or recurrent infection in my hip or knee confirmed by a fluid test.

I agree to have my prosthesis examined and replaced around 3 months later.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

TRL1068 is administered at 15 mg/kg IV on Day 1 and subsequently at 7.5 mg/kg on Days 15, 29, and 43. A DAIR procedure is completed between Day 15-22.

6 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of adverse events and efficacy measures.

52 weeks

Regular assessments up to Day 365

What Are the Treatments Tested in This Trial?

Interventions

• DAIR
• TRL1068

Trial Overview TRL1068 (calpurbatug) combined with DAIR procedure is being tested to see if it can clear infections around prosthetic joints without needing to replace the implant. This Phase 2 study aims to make pathogens more vulnerable to antibiotics by removing their protective biofilm.

How Is the Trial Designed?

Group I: TRL1068 + DAIR Experimental Treatment 2 Interventions

TRL1068 will be administered at 15 mg/kg IV on Day 1 and subsequently at 7.5 mg/kg on Days 15, 29, and 43. Between Day 15-22, a DAIR procedure will be completed.

Group II: SoC Active Control 1 Intervention

Standard of Care arm, receiving 2-stage surgery as is SoC for PJI. Reduced assessments will be done at the same timepoints as the experimental arm.

Who Is Running the Clinical Trial?

Trellis Bioscience LLC

Lead Sponsor

Trials

4

Recruited

100+

Published Research Related to This Trial

In a study of patients with deep total joint infections treated using a prosthesis retaining protocol, all infections were successfully eradicated without the need for further surgery, with a mean follow-up of 37 months.

The treatment involved a combination of surgical debridement, antibiotic-impregnated beads, and intravenous antibiotics, proving effective for early postoperative or acute hematogenous infections in selected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prosthesis retention, serial debridement, and antibiotic bead use for the treatment of infection following total joint arthroplasty. Tintle, SM., Forsberg, JA., Potter, BK., et al.[2013]

In cases where surgical removal of an infected prosthesis is not feasible, long-term oral suppressive antibiotic therapy can maintain the function of the prosthesis in 86.2% of patients over an average follow-up of 5 years.

The study found a 69% success rate for treating Staphylococcus aureus infections in prosthetic joints, indicating that while outcomes can be favorable, further research is needed to determine the best oral antibiotic regimens and treatment durations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term suppression of infection in total joint arthroplasty. Rao, N., Crossett, LS., Sinha, RK., et al.[2005]

In a review of 21 studies involving 1338 total knee arthroplasties (TKAs) in patients with hemophilia, the 5-year implant survivorship was 94%, but it declined to 76% by 15 years, indicating that while initial outcomes are good, long-term survivorship is a concern.

The infection rate in patients with hemophilia after TKA was found to be 5%, significantly higher than the 0.5-1% rate reported in the general population, although higher HIV prevalence did not correlate with increased infection rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of HIV prevalence, CD4 counts and disease severity on the outcome of total knee arthroplasty for haemophilic arthropathy: a systematic review and meta-analysis. Fu, H., Peacock, C., Wang, C., et al.[2023]

In a study of 16 patients with prosthetic joint infections diagnosed through positive intraoperative cultures, a median of 28 days of intravenous antimicrobial therapy led to an impressive 89% survival rate free of treatment failure over 5 years.

The study indicates that infections caused by low virulence pathogens can be effectively managed with shorter courses of intravenous antibiotics, suggesting that less than 6 weeks of treatment may be sufficient for certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prosthetic joint infection diagnosed postoperatively by intraoperative culture. Marculescu, CE., Berbari, EF., Hanssen, AD., et al.[2019]

The Combined Diagnostic Tool, which calculates the Combined Tests Index (CTI), effectively predicts the likelihood of joint prosthesis infection, with a significant difference in CTI values between infected (CTI >1) and non-infected patients (CTI <1).

In a study of 36 patients, all 21 with confirmed infections had a CTI above 1, while all 15 without infections had a CTI below 1, demonstrating the tool's potential as a reliable diagnostic indicator.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined Diagnostic Tool for joint prosthesis infections. Romano, CL., Romanò, D., Bonora, C., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04763759

Study to Evaluate Safety and Activity of TRL1068 in ... TRL1068 is expected to eliminate the pathogen-protecting biofilm in the prosthetic joint and surrounding tissue, thus making these pathogens substantially ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11304715/

Phase 1 study of the pharmacokinetics and clinical proof-of ... We report the results of a first-in-human phase 1 clinical study to evaluate TRL1068, a native human monoclonal antibody that disrupts bacterial ...

3. prnewswire.com prnewswire.com/news-releases/trellis-bioscience-announces-positive-interim-phase-1-results-for-trl1068-a-novel-native-human-monoclonal-antibody-which-reduces-bacterial-biofilm-burden-in-chronic-prosthetic-joint-infections-301815854.html

Trellis Bioscience Announces Positive Interim Phase 1 ... TRL1068 has the potential to disrupt bacterial biofilm and thereby enable difficult-to-treat bacterial infections to be treated with standard antibiotics.

4. withpower.com withpower.com/trial/phase-2-prosthetic-joint-infections-of-hip-2025-0c22e

TRL1068 for Prosthetic Joint Infection In a study of patients with deep total joint infections treated using a prosthesis retaining protocol, all infections were successfully eradicated without the ...

5. journals.asm.org journals.asm.org/doi/abs/10.1128/aac.00338-25?af=R

Advancing the management of 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 ...

6. journals.asm.org journals.asm.org/doi/10.1128/aac.00655-24

Phase 1 study of the pharmacokinetics and clinical proof-of ... This first-in-human study of TRL1068 was conducted in volunteers who had a chronic bacterial periprosthetic joint infection of the knee or hip.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12486824/

Advancing the management of prosthetic joint infections We extracted data regarding trial design, intervention characteristics, primary and secondary outcomes, current status, and preliminary or final ...

8. uclahealth.org uclahealth.org/clinical-trials/study-evaluate-efficacy-and-safety-trl1068-treatment

Study to Evaluate the Efficacy and Safety of TRL1068 for ... This Phase 2 study is designed to assess efficacy and safety of TRL1068 in combination with a DAIR (debridement, antibiotics, and implant retention) procedure ...

9. app.trialscreen.org app.trialscreen.org/trials/phase-2-to-evaluate-efficacy-safety-trl1068-treatment-prosthetic-joint-trial-nct06621251

Study to Evaluate the Efficacy and Safety of TRL1068 for ... A study evaluating the effectiveness and safety of TRL1068 in treating prosthetic joint infections and avoiding the need for joint replacement surgery ... Are the ...