search
Back to results

Study to Evaluate Safety and Activity of TRL1068 in Prosthetic Joint Infections

Primary Purpose

Prosthetic Joint Infection

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
TRL1068, a human monoclonal antibody
Sponsored by
Trellis Bioscience LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prosthetic Joint Infection focused on measuring biofilm, antibiotic-resistant infections

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of AlabamaRecruiting
  • USCRecruiting
  • UCLARecruiting
  • University of FloridaRecruiting
  • Gulfcoast Research InstituteRecruiting
  • Phoenix Clinical ResearchRecruiting
  • Sinai Hospital of BaltimoreRecruiting
  • Houston Methodist Research InstituteRecruiting
  • University of VirginiaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Dose Level 1- 6mg/kg

Dose Level 2- 15mg/kg

Dose Level 3- 30 mg/kg

Arm Description

Randomized 3:1 (TRL1068:placebo) via IV infusion

Randomized 5:2 (TRL1068:placebo) via IV infusion

Randomized 5:2 (TRL1068:placebo) via IV infusion

Outcomes

Primary Outcome Measures

Incidence of Abnormal Physical Examination Findings
clinically significant abnormal physical exam findings will be reviewed
Incidence of Abnormal Serum Chemistries and Hematology
clinically significant abnormal laboratory results will be reviewed
Incidence of Abnormal Vital Signs (Temperature)
clinically significant abnormal temperatures will be reviewed
Incidence of Abnormal Vital Signs (Blood Pressure)
clinically significant abnormal blood pressures will be reviewed
Incidence of Abnormal Vital Signs (Heart Rate)
clinically significant abnormal heart rates will be reviewed
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
mortality and any other reported AEs and SAEs will be reviewed

Secondary Outcome Measures

Characterize the pharmacokinetics (PK) of a single IV infusion of TRL1068
Serum and synovial concentrations of TRL1068 will be determined by ELISA
Measure TRL1068 levels in synovial fluid on Day 8 and compare with plasma PK
Serum and synovial concentrations of TRL1068 will be determined by ELISA
Assess the pharmacodynamics (PD) of TRL1068 (Colony Forming Units (CFUs) prosthesis)
Number of CFUs from sonicated prosthetic device
Assess the pharmacodynamics (PD) of TRL1068 (CFUs spacer)
Number of CFUs from sonicated orthopedic spacer
Assess the pharmacodynamics (PD) of TRL1068 (CRP)
Inflammatory biomarker CRP
Assess the pharmacodynamics (PD) of TRL1068 (ESR)
Inflammatory biomarker ESR
Assess the pharmacodynamics (PD) of TRL1068 (IL-6)
Inflammatory biomarker IL-6
Assess the pharmacodynamics (PD) of TRL1068 (IL-10)
Inflammatory biomarker IL-10
Assess the pharmacodynamics (PD) of TRL1068 (reinfection)
Assessment for reinfection including need for further surgical interventions and overall outcome
Assess the immunogenicity of TRL1068 as measured by anti-drug antibodies (ADAs)
Anti-drug antibodies (ADA), i.e. anti-TRL1068 antibodies in serum will determined by electrochemiluminescence assay.

Full Information

First Posted
February 12, 2021
Last Updated
April 25, 2023
Sponsor
Trellis Bioscience LLC
Collaborators
University of California, Los Angeles, Biomedical Advanced Research and Development Authority, Wellcome Trust, Sinai Hospital of Baltimore, Gulfcoast Research Institute, Phoenix Clinical Research, University of Florida, University of Alabama at Birmingham, The Methodist Hospital Research Institute, University of Virginia, University of Southern California
search

1. Study Identification

Unique Protocol Identification Number
NCT04763759
Brief Title
Study to Evaluate Safety and Activity of TRL1068 in Prosthetic Joint Infections
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 8, 2021 (Actual)
Primary Completion Date
November 2023 (Anticipated)
Study Completion Date
February 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Trellis Bioscience LLC
Collaborators
University of California, Los Angeles, Biomedical Advanced Research and Development Authority, Wellcome Trust, Sinai Hospital of Baltimore, Gulfcoast Research Institute, Phoenix Clinical Research, University of Florida, University of Alabama at Birmingham, The Methodist Hospital Research Institute, University of Virginia, University of Southern California

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prosthetic Joint Infection
Keywords
biofilm, antibiotic-resistant infections

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Model Description
Phase 1, Double-Blinded, Single Ascending Dose Study
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
The study is double-blind and placebo-controlled.
Allocation
Randomized
Enrollment
18 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Dose Level 1- 6mg/kg
Arm Type
Experimental
Arm Description
Randomized 3:1 (TRL1068:placebo) via IV infusion
Arm Title
Dose Level 2- 15mg/kg
Arm Type
Experimental
Arm Description
Randomized 5:2 (TRL1068:placebo) via IV infusion
Arm Title
Dose Level 3- 30 mg/kg
Arm Type
Experimental
Arm Description
Randomized 5:2 (TRL1068:placebo) via IV infusion
Intervention Type
Drug
Intervention Name(s)
TRL1068, a human monoclonal antibody
Intervention Description
A human IgG1κ (G1m1,17 (z,a); Km3 allotype) monoclonal antibody
Primary Outcome Measure Information:
Title
Incidence of Abnormal Physical Examination Findings
Description
clinically significant abnormal physical exam findings will be reviewed
Time Frame
16 weeks
Title
Incidence of Abnormal Serum Chemistries and Hematology
Description
clinically significant abnormal laboratory results will be reviewed
Time Frame
16 weeks
Title
Incidence of Abnormal Vital Signs (Temperature)
Description
clinically significant abnormal temperatures will be reviewed
Time Frame
16 weeks
Title
Incidence of Abnormal Vital Signs (Blood Pressure)
Description
clinically significant abnormal blood pressures will be reviewed
Time Frame
16 weeks
Title
Incidence of Abnormal Vital Signs (Heart Rate)
Description
clinically significant abnormal heart rates will be reviewed
Time Frame
16 weeks
Title
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
mortality and any other reported AEs and SAEs will be reviewed
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Characterize the pharmacokinetics (PK) of a single IV infusion of TRL1068
Description
Serum and synovial concentrations of TRL1068 will be determined by ELISA
Time Frame
16 weeks
Title
Measure TRL1068 levels in synovial fluid on Day 8 and compare with plasma PK
Description
Serum and synovial concentrations of TRL1068 will be determined by ELISA
Time Frame
1 week
Title
Assess the pharmacodynamics (PD) of TRL1068 (Colony Forming Units (CFUs) prosthesis)
Description
Number of CFUs from sonicated prosthetic device
Time Frame
1 week
Title
Assess the pharmacodynamics (PD) of TRL1068 (CFUs spacer)
Description
Number of CFUs from sonicated orthopedic spacer
Time Frame
12 weeks
Title
Assess the pharmacodynamics (PD) of TRL1068 (CRP)
Description
Inflammatory biomarker CRP
Time Frame
16 weeks
Title
Assess the pharmacodynamics (PD) of TRL1068 (ESR)
Description
Inflammatory biomarker ESR
Time Frame
16 weeks
Title
Assess the pharmacodynamics (PD) of TRL1068 (IL-6)
Description
Inflammatory biomarker IL-6
Time Frame
16 weeks
Title
Assess the pharmacodynamics (PD) of TRL1068 (IL-10)
Description
Inflammatory biomarker IL-10
Time Frame
16 weeks
Title
Assess the pharmacodynamics (PD) of TRL1068 (reinfection)
Description
Assessment for reinfection including need for further surgical interventions and overall outcome
Time Frame
24 weeks
Title
Assess the immunogenicity of TRL1068 as measured by anti-drug antibodies (ADAs)
Description
Anti-drug antibodies (ADA), i.e. anti-TRL1068 antibodies in serum will determined by electrochemiluminescence assay.
Time Frame
16 weeks
Other Pre-specified Outcome Measures:
Title
Exploratory outcome measure to determine CFUs
Description
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.
Time Frame
12 weeks
Title
Exploratory outcome measure to determine inflammation (CRP)
Description
The mean levels of C reactive protein (CRP) from placebo and TRL1068 treated groups will be compared.
Time Frame
16 weeks
Title
Exploratory outcome measure to determine inflammation (ESR)
Description
The mean levels of erythrocyte sedimentation rate (ESR) from placebo and TRL1068 treated groups will be compared.
Time Frame
16 weeks
Title
Exploratory outcome measure to determine inflammation (IL-6)
Description
The mean levels of Interleukin-6 (IL-6) from placebo and TRL1068 treated groups will be compared.
Time Frame
16 weeks
Title
Exploratory outcome measure to determine inflammation (IL-10)
Description
The mean levels of Interleukin-10 (IL-10) from placebo and TRL1068 treated groups will be compared.
Time Frame
16 weeks
Title
Exploratory outcome measure to determine infection in synovial fluid
Description
The number of subjects with CFUs/mL ≥ 1 from the synovial fluid from placebo and TRL1068 treated groups will be compared.
Time Frame
1 week
Title
Exploratory outcome measure inflammation in the synovial fluid
Description
The mean synovial fluid total leukocyte cell counts of the consolidated placebo and TRL1068 treated groups will be compared.
Time Frame
1 week
Title
Exploratory outcome measure to assess quality of life
Description
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.
Time Frame
24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Anton (Tony) Leighton, MD
Phone
650-838-1400
Email
Clinicalstudies@trellisbio.com
First Name & Middle Initial & Last Name or Official Title & Degree
Adriane Kisch-Hancock
Phone
650-838-1400
Email
akisch-hancock@trellisbio.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nicholas Bernthal, MD
Organizational Affiliation
University of California, Los Angeles
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Janet Conway, MD
Organizational Affiliation
Sinai Hospital of Baltimore
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Edward Stolarski, MD
Organizational Affiliation
Gulfcoast Research Institute
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Richard Berkowitz, MD
Organizational Affiliation
Phoenix Clinical Research
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Luis Pulido, MD
Organizational Affiliation
University of Florida
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Sameer Naranje, MD
Organizational Affiliation
University of Alabama at Birmingham
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Stephen Incavo, MD
Organizational Affiliation
The Methodist Hospital Research Institute
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ian Duensing, MD
Organizational Affiliation
UVA
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Daniel Oakes, MD
Organizational Affiliation
University of Southern California
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35205
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Melanese Leonard-Warren
Phone
205-490-4179
Email
mnleonard@uabmc.edu
First Name & Middle Initial & Last Name & Degree
Sameer Naranje, MD
Facility Name
USC
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pui Yan, CCRP
Phone
714-470-0614
Email
puiyan@med.usc.edu
First Name & Middle Initial & Last Name & Degree
Daniel Oakes, MD
Facility Name
UCLA
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nicholas Bernthal, MD
First Name & Middle Initial & Last Name & Degree
Edward McPherson, MD
First Name & Middle Initial & Last Name & Degree
Erik Zeegen, MD
First Name & Middle Initial & Last Name & Degree
Adam Sassoon, MD
First Name & Middle Initial & Last Name & Degree
Alexandra Stavrakis, MD
First Name & Middle Initial & Last Name & Degree
Bert Thomas, MD
First Name & Middle Initial & Last Name & Degree
Claire Brown, MD
First Name & Middle Initial & Last Name & Degree
Noah Federman, MD
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32611
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Emilie Miley
Phone
352-273-7361
Email
mileyen@ortho.ufl.edu
First Name & Middle Initial & Last Name & Degree
Luis Pulido, MD
Facility Name
Gulfcoast Research Institute
City
Sarasota
State/Province
Florida
ZIP/Postal Code
34232
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jesse D'Alessio, CCRC
Phone
941-552-7875
Email
jdalessio@gulfcoast-research.com
First Name & Middle Initial & Last Name & Degree
Edward Stolarski, MD
Facility Name
Phoenix Clinical Research
City
Tamarac
State/Province
Florida
ZIP/Postal Code
33321
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Steffanie Littleton, ACRP-CP
Phone
561-715-8188
Email
s.littleton@phoenixclinical.com
First Name & Middle Initial & Last Name & Degree
Richard Berkowitz, MD
Facility Name
Sinai Hospital of Baltimore
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21215
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Janet Conway, MD
First Name & Middle Initial & Last Name & Degree
Ronald Delanois, MD
First Name & Middle Initial & Last Name & Degree
James Nace, DO
Facility Name
Houston Methodist Research Institute
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thomas Sullivan, CCRC
Phone
346-238-1603
Email
tsullivan@houstonmethodist.org
First Name & Middle Initial & Last Name & Degree
Stephen Incavo, MD
Facility Name
University of Virginia
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22903
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eric McVey
Phone
434-243-5382
Email
emcvey@virginia.edu
First Name & Middle Initial & Last Name & Degree
Ian Duensing, MD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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
Citations:
PubMed Identifier
26833157
Citation
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.
Results Reference
background
PubMed Identifier
28717038
Citation
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.
Results Reference
background

Learn more about this trial

Study to Evaluate Safety and Activity of TRL1068 in Prosthetic Joint Infections

We'll reach out to this number within 24 hrs