Study to Evaluate the Efficacy and Safety of TRL1068 for the Treatment of Prosthetic Joint Infection

NCT06621251 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: TRL1068-201
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 11

Brief Summary

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.

Conditions

Prosthetic Joint Infections of Knee; Prosthetic Joint Infections of Hip

Keywords

biofilm; antibiotic-resistant infections

Outcome Measures

Primary Outcomes (1)

• Efficacy of TRL1068 in eliminating the need for an SoC 2-stage exchange arthroplasty

  Incidence of resolved PJI, i.e., completion of planned surgical interventions for PJI (DAIR or 2-stage exchange arthroplasty), and not receiving systemic antibiotics for PJI or antibiotic suppression therapy for PJI or any other planned interventions to treat PJI by end of study.

  Day 365

Secondary Outcomes (9)

• Duration (days) with resolved PJI

  Day 365

• Incidence of recurrent PJI across treatment groups

  Day 365

• Incidence of PJI reinfection across treatment groups

  Day 365

• Incidence, duration and severity of AEs or SAEs of secondary infections

  Day 365

• Musculoskeletal Infection Society (MSIS) Scores

  Day 365

Other Outcomes (4)

• Immunogenicity of TRL1068 as measured by anti-drug antibodies (ADAs)

  Day 365

• Pharmacokinetics - serum and synovial concentrations of TRL1068

  Day 365

• Pharmacodynamics - inflammatory biomarkers - CRP

  Day 365

Study Arms (2)

TRL1068 + DAIR

EXPERIMENTAL

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.

Drug: TRL1068 (calpurbatug), a human monoclonal antibody; Procedure: DAIR

SoC

NO 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.

Interventions

TRL1068 (calpurbatug), a human monoclonal antibody DRUG

A human IgG1κ (G1m1,17 (z,a); Km3 allotype) monoclonal antibody

TRL1068 + DAIR

DAIR PROCEDURE

DAIR procedure will be performed between days 15-22

Also known as: debridement, antibiotics, and implant retention

TRL1068 + DAIR

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 85 years, inclusive
• Chronic PJI:
• Systemic Host Grade of A or B \[McPherson 2011\] (Appendix 3) and either
• First chronic PJI of the hip or knee, confirmed by synovial fluid aspirate culture or
• Recurrent chronic PJI of the hip or knee confirmed by synovial fluid aspirate culture
• Willing to be randomized to either:
• 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
• 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)
• 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)
• All identified pathogen(s) are susceptible to the planned antibiotic regimen
• Availability of radiology assessments of the affected joint without signs of loosening of the prosthesis or presence of osteomyelitis
• Willing and able to provide written informed consent
• Willing to perform and comply with all study procedures, including attending clinic visits as scheduled
• 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.

You may not qualify if:

• 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.
• More than one draining sinus and single draining sinus of \> 1 cm
• Less than 3 years life expectancy based on underlying morbidities
• Expected to receive chronic suppressive antibiotic therapy
• Congestive heart failure; New York Heart Association (NYHA) Functional Classification of Heart Failure Grade \> 3B
• Uncontrolled diabetes, defined as hemoglobin A1c \> 7.4%.
• BMI \> 45
• 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
• Receiving or recently received another investigational drug (within 30 days of Day 1, or 5 half-lives of the investigational drug, whichever is longer)
• Received any vaccine within 14 days prior to Day 1
• Positive serum pregnancy test for WOCBP, or nursing women
• 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
• 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.

Sponsors & Collaborators

• Trellis Bioscience LLC: lead

Study Sites (11)

OrthoArizona

Gilbert, Arizona, 85234, United States

Location

UCLA

Los Angeles, California, 90024, United States

Location

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

Location

Gulfcoast Research Institute

Sarasota, Florida, 34232, United States

Location

Phoenix Clinical Research

Tamarac, Florida, 33321, United States

Location

Sinai Hospital Baltimore

Baltimore, Maryland, 21215, United States

Location

New England Baptist Hospital

Boston, Massachusetts, 02120, United States

Location

University of Rochester

Rochester, New York, 14623, United States

Location

M3 Wake Research Associates

Wilmington, North Carolina, 28412, United States

Location

North Texas Medical Research Institute

Rockwall, Texas, 75087, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Related Publications (1)

• Conway J, Delanois RE, Mont MA, Stavrakis A, McPherson E, Stolarski E, Incavo S, Oakes D, Salvagno R, Adams JS, Kisch-Hancock A, Tenorio E, Leighton A, Ryser S, Kauvar LM, Bernthal NM. Phase 1 study of the pharmacokinetics and clinical proof-of-concept activity of a biofilm-disrupting human monoclonal antibody in patients with chronic prosthetic joint infection of the knee or hip. Antimicrob Agents Chemother. 2024 Aug 7;68(8):e0065524. doi: 10.1128/aac.00655-24. Epub 2024 Jul 16.

  PMID: 39012102 RESULT

MeSH Terms

Interventions

TRL1068; Debridement; Anti-Bacterial Agents

Intervention Hierarchy (Ancestors)

Surgical Procedures, Operative; Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2024
• First Posted: October 1, 2024
• Study Start: April 8, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: May 7, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)