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

November 18, 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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
15

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • United States
    • 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
      • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Dose Level 1- 6mg/kg
Randomized 3:1 (TRL1068:placebo) via IV infusion
Drug: TRL1068, a human monoclonal antibody
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
Drug: TRL1068, a human monoclonal antibody
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
Drug: TRL1068, a human monoclonal antibody
A human IgG1κ (G1m1,17 (z,a); Km3 allotype) monoclonal antibody

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Trellis Bioscience LLC

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of California, Los Angeles
University of Alabama at Birmingham
University of Florida
University of Southern California
Wellcome Trust
University of Virginia
The Methodist Hospital Research Institute
Biomedical Advanced Research and Development Authority
Phoenix Clinical Research
Sinai Hospital of Baltimore
Gulfcoast Research Institute

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 8, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 13, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 13, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 12, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 18, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 21, 2021

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 21, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 18, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • TRL1068-101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

The study results have been published.

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

product manufactured in and exported from the U.S.

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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