TRL1068 for Prosthetic Joint Infection

Recruiting at 9 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

Trial Summary

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.

What data supports the effectiveness of the treatment TRL1068 for Prosthetic Joint Infection?

The research shows that a similar treatment approach, involving surgical cleaning and antibiotics, successfully eradicated infections in patients with prosthetic joint infections, allowing them to keep their joint implants. This suggests that TRL1068, when used with similar methods, might also be effective in treating these infections. ^{1 2 3 4 5}

What is the purpose of this trial?

TRL1068 is expected to eliminate the pathogen-protecting biofilm in the prosthetic joint and surrounding tissue, thus making pathogens substantially more susceptible to established antibiotic treatment regimens. This Phase 2 study is designed to assess efficacy and safety of TRL1068 in combination with a DAIR (debridement, antibiotics, and implant retention) procedure for chronic prosthetic joint infections of the knee and hip, specifically, eliminating the need for the standard of care 2-stage exchange surgery, so that the original prosthesis can be retained.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Prosthesis retention, serial debridement, and antibiotic bead use for the treatment of infection following total joint arthroplasty. [2013]

2. Italy pubmed.ncbi.nlm.nih.gov

Combined Diagnostic Tool for joint prosthesis infections. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Prosthetic joint infection diagnosed postoperatively by intraoperative culture. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Long-term suppression of infection in total joint arthroplasty. [2005]

5. France 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. [2023]