- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04763759
Study to Evaluate Safety and Activity of TRL1068 in Prosthetic Joint Infections
April 8, 2024 updated by: Trellis Bioscience LLC
A Phase 1, Blinded, Single Ascending Dose Study to Evaluate Safety, Pharmacokinetics, and Activity of TRL1068 in Subjects With Prosthetic Joint Infection of the Knee or Hip, Undergoing Primary Two Stage Exchange Arthroplasty
TRL1068 is expected to eliminate the pathogen-protecting biofilm in the prosthetic joint and surrounding tissue, thus making these pathogens substantially more susceptible to established antibiotic treatment regimens.
This initial study is designed to assess overall safety and pharmacokinetics (PK) of TRL1068.
The overall goal of the development program is to demonstrate that TRL1068 can facilitate effectiveness of a single stage joint replacement or preservation of the original infected prosthetic joint in a substantial proportion of patients with PJI.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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 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 (Actual)
15
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Alabama
-
Birmingham, Alabama, United States, 35205
- University of Alabama
-
-
California
-
Los Angeles, California, United States, 90033
- USC
-
Santa Monica, California, United States, 90404
- UCLA
-
-
Florida
-
Gainesville, Florida, United States, 32611
- University of Florida
-
Sarasota, Florida, United States, 34232
- Gulfcoast Research Institute
-
Tamarac, Florida, United States, 33321
- Phoenix Clinical Research
-
-
Maryland
-
Baltimore, Maryland, United States, 21215
- Sinai Hospital of Baltimore
-
-
Texas
-
Houston, Texas, United States, 77030
- Houston Methodist Research Institute
-
-
Virginia
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Charlottesville, Virginia, United States, 22903
- University of Virginia
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 85 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Diagnosis of PJI of the knee or hip
- Identified pathogen(s) must be susceptible to antibiotic regimen
- Planned/scheduled for primary two-stage exchange arthroplasty
- BMI < 40 kg/m²
- 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 child bearing potential (WOCBP) must be willing to practice a highly effective method of contraception
Exclusion Criteria:
- Evidence of active infection other than bacterial PJI of the knee or hip
- Inability to receive or intolerant to pathogen-appropriate systemic or oral antibiotic therapy
- Chronic obstructive pulmonary disease (COPD)
- Child-Pugh score > 6
- Congestive heart failure
- Immunocompromised individuals, including those receiving immunosuppressive doses of corticosteroids
- Active malignancy, or history of malignancy or chemotherapy within the past 2 years
- Active or history of autoimmune disease
- Uncontrolled diabetes, defined as hemoglobin A1c > 7.4%
- Clinically significant abnormality on electrocardiogram (ECG) that would preclude subject from undergoing two-stage exchange arthroplasty
- Clinically significant serum chemistry or hematology abnormalities
- Any acute illness within 14 days of Day 1 that could confound the evaluation of safety evaluation
- Known or suspected intolerance or hypersensitivity to any biologic medication
- Received a therapeutic antibody or biologic within the 6 months prior to Screening
- Positive serum test for pregnancy, pregnant, or nursing women
- Positive reverse transcription polymerase chain reaction (RT -PCR) or alternative (antigen) test for acute respiratory syndrome coronavirus 2
- History of drug or alcohol abuse that, in the opinion of the Investigator, would interfere with the subject's ability to comply with the study requirements
- Any other comorbidity or condition that, in the opinion of the Investigator would make the subject unsuitable for the study or unable to comply with the study requirements
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Dose Level 1- 6mg/kg
Randomized 3:1 (TRL1068:placebo) via IV infusion
|
A human IgG1κ (G1m1,17 (z,a); Km3 allotype) monoclonal antibody
|
Experimental: Dose Level 2- 15mg/kg
Randomized 5:2 (TRL1068:placebo) via IV infusion
|
A human IgG1κ (G1m1,17 (z,a); Km3 allotype) monoclonal antibody
|
Experimental: Dose Level 3- 30 mg/kg
Randomized 5:2 (TRL1068:placebo) via IV infusion
|
A human IgG1κ (G1m1,17 (z,a); Km3 allotype) monoclonal antibody
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of Abnormal Physical Examination Findings
Time Frame: 16 weeks
|
clinically significant abnormal physical exam findings will be reviewed
|
16 weeks
|
Incidence of Abnormal Serum Chemistries and Hematology
Time Frame: 16 weeks
|
clinically significant abnormal laboratory results will be reviewed
|
16 weeks
|
Incidence of Abnormal Vital Signs (Temperature)
Time Frame: 16 weeks
|
clinically significant abnormal temperatures will be reviewed
|
16 weeks
|
Incidence of Abnormal Vital Signs (Blood Pressure)
Time Frame: 16 weeks
|
clinically significant abnormal blood pressures will be reviewed
|
16 weeks
|
Incidence of Abnormal Vital Signs (Heart Rate)
Time Frame: 16 weeks
|
clinically significant abnormal heart rates will be reviewed
|
16 weeks
|
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: 24 weeks
|
mortality and any other reported AEs and SAEs will be reviewed
|
24 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Characterize the pharmacokinetics (PK) of a single IV infusion of TRL1068
Time Frame: 16 weeks
|
Serum and synovial concentrations of TRL1068 will be determined by ELISA
|
16 weeks
|
Measure TRL1068 levels in synovial fluid on Day 8 and compare with plasma PK
Time Frame: 1 week
|
Serum and synovial concentrations of TRL1068 will be determined by ELISA
|
1 week
|
Assess the pharmacodynamics (PD) of TRL1068 (Colony Forming Units (CFUs) prosthesis)
Time Frame: 1 week
|
Number of CFUs from sonicated prosthetic device
|
1 week
|
Assess the pharmacodynamics (PD) of TRL1068 (CFUs spacer)
Time Frame: 12 weeks
|
Number of CFUs from sonicated orthopedic spacer
|
12 weeks
|
Assess the pharmacodynamics (PD) of TRL1068 (CRP)
Time Frame: 16 weeks
|
Inflammatory biomarker CRP
|
16 weeks
|
Assess the pharmacodynamics (PD) of TRL1068 (ESR)
Time Frame: 16 weeks
|
Inflammatory biomarker ESR
|
16 weeks
|
Assess the pharmacodynamics (PD) of TRL1068 (IL-6)
Time Frame: 16 weeks
|
Inflammatory biomarker IL-6
|
16 weeks
|
Assess the pharmacodynamics (PD) of TRL1068 (IL-10)
Time Frame: 16 weeks
|
Inflammatory biomarker IL-10
|
16 weeks
|
Assess the pharmacodynamics (PD) of TRL1068 (reinfection)
Time Frame: 24 weeks
|
Assessment for reinfection including need for further surgical interventions and overall outcome
|
24 weeks
|
Assess the immunogenicity of TRL1068 as measured by anti-drug antibodies (ADAs)
Time Frame: 16 weeks
|
Anti-drug antibodies (ADA), i.e. anti-TRL1068 antibodies in serum will determined by electrochemiluminescence assay.
|
16 weeks
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Exploratory outcome measure to determine CFUs
Time Frame: 12 weeks
|
The number of subjects with Colony Forming Units (CFUs) per mL ≥ 1 from sonicated prosthetic devices from placebo and TRL1068 treated groups will be compared.
|
12 weeks
|
Exploratory outcome measure to determine inflammation (CRP)
Time Frame: 16 weeks
|
The mean levels of C reactive protein (CRP) from placebo and TRL1068 treated groups will be compared.
|
16 weeks
|
Exploratory outcome measure to determine inflammation (ESR)
Time Frame: 16 weeks
|
The mean levels of erythrocyte sedimentation rate (ESR) from placebo and TRL1068 treated groups will be compared.
|
16 weeks
|
Exploratory outcome measure to determine inflammation (IL-6)
Time Frame: 16 weeks
|
The mean levels of Interleukin-6 (IL-6) from placebo and TRL1068 treated groups will be compared.
|
16 weeks
|
Exploratory outcome measure to determine inflammation (IL-10)
Time Frame: 16 weeks
|
The mean levels of Interleukin-10 (IL-10) from placebo and TRL1068 treated groups will be compared.
|
16 weeks
|
Exploratory outcome measure to determine infection in synovial fluid
Time Frame: 1 week
|
The number of subjects with CFUs/mL ≥ 1 from the synovial fluid from placebo and TRL1068 treated groups will be compared.
|
1 week
|
Exploratory outcome measure inflammation in the synovial fluid
Time Frame: 1 week
|
The mean synovial fluid total leukocyte cell counts of the consolidated placebo and TRL1068 treated groups will be compared.
|
1 week
|
Exploratory outcome measure to assess quality of life
Time Frame: 24 weeks
|
Patient-Reported Outcomes Measurement Information System - Physical Function (PROMIS-PF) Short Form 6b from placebo and TRL1068 treated groups will be compared.
This questionnaire has a score range from 6-30, with higher scores indicating higher functioning than lower scores.
|
24 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Stephen Incavo, MD, The Methodist Hospital Research Institute
- Principal Investigator: Sameer Naranje, MD, University of Alabama at Birmingham
- Principal Investigator: Ian Duensing, MD, UVA
- Principal Investigator: Daniel Oakes, MD, University of Southern California
- Principal Investigator: Nicholas Bernthal, MD, University of California, Los Angeles
- Principal Investigator: Janet Conway, MD, Sinai Hospital of Baltimore
- Principal Investigator: Edward Stolarski, MD, Gulfcoast Research Institute
- Principal Investigator: Richard Berkowitz, MD, Phoenix Clinical Research
- Principal Investigator: Luis Pulido, MD, University of Florida
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Estelles A, Woischnig AK, Liu K, Stephenson R, Lomongsod E, Nguyen D, Zhang J, Heidecker M, Yang Y, Simon RJ, Tenorio E, Ellsworth S, Leighton A, Ryser S, Gremmelmaier NK, Kauvar LM. A High-Affinity Native Human Antibody Disrupts Biofilm from Staphylococcus aureus Bacteria and Potentiates Antibiotic Efficacy in a Mouse Implant Infection Model. Antimicrob Agents Chemother. 2016 Mar 25;60(4):2292-301. doi: 10.1128/AAC.02588-15. Print 2016 Apr.
- Xiong YQ, Estelles A, Li L, Abdelhady W, Gonzales R, Bayer AS, Tenorio E, Leighton A, Ryser S, Kauvar LM. A Human Biofilm-Disrupting Monoclonal Antibody Potentiates Antibiotic Efficacy in Rodent Models of both Staphylococcus aureus and Acinetobacter baumannii Infections. Antimicrob Agents Chemother. 2017 Sep 22;61(10):e00904-17. doi: 10.1128/AAC.00904-17. Print 2017 Oct.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
February 8, 2021
Primary Completion (Actual)
March 13, 2024
Study Completion (Actual)
March 13, 2024
Study Registration Dates
First Submitted
February 12, 2021
First Submitted That Met QC Criteria
February 18, 2021
First Posted (Actual)
February 21, 2021
Study Record Updates
Last Update Posted (Actual)
April 10, 2024
Last Update Submitted That Met QC Criteria
April 8, 2024
Last Verified
April 1, 2024
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- TRL1068-101
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
We plan to make the Clinical Protocol and SAP available on Protocols.io
(https://www.protocols.io/)
before trial recruitment is complete.
IPD Sharing Time Frame
Before trial recruitment is complete on Protocols.io
(https://www.protocols.io/)
IPD Sharing Access Criteria
available
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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