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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Prosthetic Joint Infections of Hip; Prosthetic Joint Infections of Knee
• Intervention / Treatment: Drug: TRL1068 (calpurbatug), a human monoclonal antibody; Procedure: DAIR

Detailed Description

Approximately 75% of all clinically significant human infections are estimated to be biofilm-related. Prosthetic joint infections are a classical example of difficult to eradicate infections associated with biofilm. Most Prosthetic Joint Infection (PJI) cases are caused by staphylococcal species (~70%) with an increasing number being antibiotic-resistant (MRSA). In the US, two-stage revision is the standard of care for replacement of an infected prosthetic joint, and is associated with substantial costs and prolonged immobility. TRL1068 is a fully human antibody that has been shown in pre-clinical studies and in the first-in-human Phase 1 study TRL1068-101 to disrupt biofilm. TRL1068 targets a highly conserved epitope on the DNABII family of bacterial DNA binding proteins that includes histone-like (HU) and integration host factor (IHF) proteins of clinically relevant Gram-positive and Gram-negative bacteria. The DNABII epitope bound by TRL1068 has no homologs in the human proteome.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • OrthoArizona
  • California
    • Los Angeles, California, United States, 90024
      • UCLA
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Jacksonville
    • Sarasota, Florida, United States, 34232
      • Gulfcoast Research Institute
    • Tamarac, Florida, United States, 33321
      • Phoenix Clinical Research
  • Maryland
    • Baltimore, Maryland, United States, 21215
      • Sinai Hospital Baltimore
  • Massachusetts
    • Boston, Massachusetts, United States, 02120
      • New England Baptist Hospital
  • New York
    • Rochester, New York, United States, 14623
      • University of Rochester
  • North Carolina
    • Wilmington, North Carolina, United States, 28412
      • M3 Wake Research Associates
  • Texas
    • Rockwall, Texas, United States, 75087
      • North Texas Medical Research Institute
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TRL1068 + DAIR; 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; A human IgG1κ (G1m1,17 (z,a); Km3 allotype) monoclonal antibody; Procedure: DAIR; DAIR procedure will be performed between days 15-22; Other Names: debridement, antibiotics, and implant retention
No Intervention: SoC; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration (days) with resolved PJI	Days after completion of planned surgical interventions for PJI (DAIR or 2-stage exchange arthroplasty) without receiving systemic antibiotics for PJI or antibiotic suppression therapy of PJI or any other planned interventions to treat PJI by end of study.	Day 365
Incidence of recurrent PJI across treatment groups	Recurrent PJI will include PJI in which the causative pathogen of the recurrent PJI was not identified at baseline.	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	MSIS scores on Day 1, day of DAIR (Day 15 + 7 days) versus Day 1, day of first stage of SoC and EOS (Day 365) that are indicative of the presence of PJI. MSIS Minor Criteria score range is 0-12, above or equal to 6 is infected, 2-5 is possibly infected, 0-1 is not infected.	Day 365
Resource utilization: duration of hospitalization as a result of PJI, SoC or surgical wound infection		Day 365
Resource utilization: need to stay in a rehabilitation center or other institution, e.g., nursing home as a result of PJI, SoC or surgical wound infection		Day 365
Incidence, duration and severity of AEs and SAEs across treatment groups	abnormal vital signs and safety labs will be documented as adverse events.	Day 365
Quality of life PROMIS-PF Short Form 6b	Quality of life as measured by the Quality of Life (QoL) Questionnaire (PROMIS-PF Short Form 6b). Score range is 6-30, with higher scores indicating higher functioning.	Day 365

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamics - inflammatory biomarkers - CRP	CRP will be compared within and across groups	Day 365
Pharmacodynamics - inflammatory biomarkers - ESR	ESR will be compared within and across groups	Day 365
Immunogenicity of TRL1068 as measured by anti-drug antibodies (ADAs)	The exploratory objective is to assess the immunogenicity of TRL1068 as measured by anti-drug antibodies (ADAs).	Day 365
Pharmacokinetics - serum and synovial concentrations of TRL1068	Serum and synovial concentrations of TRL1068 will be determined by ELISA	Day 365

Collaborators and Investigators

• Sponsor: Trellis Bioscience LLC

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: September 26, 2024
• First Submitted That Met QC Criteria: September 27, 2024
• First Posted (Actual): October 1, 2024

Study Record Updates

• Last Update Posted (Actual): May 7, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: biofilm; antibiotic-resistant infections
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Pathologic Processes; Disease Attributes; Arthritis; Joint Diseases; Infections; Communicable Diseases; Arthritis, Infectious; Anti-Infective Agents; Surgical Procedures, Operative; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Anti-Bacterial Agents; TRL1068; Debridement
• Other Study ID Numbers: TRL1068-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The study results will be published after the study is completed.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No