Study to Evaluate the Efficacy and Safety of TRL1068 for the Treatment of Prosthetic Joint Infection
Purpose
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 Hip
- Prosthetic Joint Infections of Knee
Eligibility
- Eligible Ages
- Between 18 Years and 85 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- 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
- 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 Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
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. |
|
|
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. |
|
Recruiting Locations
Gilbert 5295903, Arizona 5551752 85234
Little Rock 4119403, Arkansas 4099753 72205
Los Angeles 5368361, California 5332921 90024
Jacksonville 4160021, Florida 4155751 32224
Tamarac 4174738, Florida 4155751 33321
Baltimore 4347778, Maryland 4361885 21215
Boston 4930956, Massachusetts 6254926 02120
New York 5128581, New York 5128638 10003
Rochester 5134086, New York 5128638 14623
Wilmington 4499379, North Carolina 4482348 28412
Galveston 4692883, Texas 4736286 77555
Houston 4699066, Texas 4736286 77030
Houston 4699066, Texas 4736286 77030
Rockwall 4723406, Texas 4736286 75087
Salt Lake City 5780993, Utah 5549030 84112
More Details
- NCT ID
- NCT06621251
- Status
- Recruiting
- Sponsor
- Trellis Bioscience LLC
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.