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

NCT04763759 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: TRL1068-101
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 9

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.

Conditions

Prosthetic Joint Infection

Keywords

biofilm; antibiotic-resistant infections

Outcome Measures

Primary Outcomes (6)

• Incidence of Abnormal Physical Examination Findings

  clinically significant abnormal physical exam findings will be reviewed

  16 weeks

• Incidence of Abnormal Serum Chemistries and Hematology

  clinically significant abnormal laboratory results will be reviewed

  16 weeks

• Incidence of Abnormal Vital Signs (Temperature)

  clinically significant abnormal temperatures will be reviewed

  16 weeks

• Incidence of Abnormal Vital Signs (Blood Pressure)

  clinically significant abnormal blood pressures will be reviewed

  16 weeks

• Incidence of Abnormal Vital Signs (Heart Rate)

  clinically significant abnormal heart rates will be reviewed

  16 weeks

• Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)

  mortality and any other reported AEs and SAEs will be reviewed

  24 weeks

Secondary Outcomes (10)

• Characterize the pharmacokinetics (PK) of a single IV infusion of TRL1068

  16 weeks

• Measure TRL1068 levels in synovial fluid on Day 8 and compare with plasma PK

  1 week

• Assess the pharmacodynamics (PD) of TRL1068 (Colony Forming Units (CFUs) prosthesis)

  1 week

• Assess the pharmacodynamics (PD) of TRL1068 (CFUs spacer)

  12 weeks

• Assess the pharmacodynamics (PD) of TRL1068 (CRP)

  16 weeks

Other Outcomes (8)

• Exploratory outcome measure to determine CFUs

  12 weeks

• Exploratory outcome measure to determine inflammation (CRP)

  16 weeks

• Exploratory outcome measure to determine inflammation (ESR)

  16 weeks

Study Arms (3)

Dose Level 1- 6mg/kg

EXPERIMENTAL

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

Drug: TRL1068, a human monoclonal antibody

Dose Level 2- 15mg/kg

EXPERIMENTAL

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

Drug: TRL1068, a human monoclonal antibody

Dose Level 3- 30 mg/kg

EXPERIMENTAL

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

Drug: TRL1068, a human monoclonal antibody

Interventions

TRL1068, a human monoclonal antibody DRUG

A human IgG1κ (G1m1,17 (z,a); Km3 allotype) monoclonal antibody

Dose Level 1- 6mg/kg; Dose Level 2- 15mg/kg; Dose Level 3- 30 mg/kg

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Trellis Bioscience LLC: lead
• University of California, Los Angeles: collaborator
• Biomedical Advanced Research and Development Authority: collaborator
• Wellcome Trust: collaborator
• Sinai Hospital of Baltimore: collaborator
• Gulfcoast Research Institute: collaborator
• Phoenix Clinical Research: collaborator
• University of Florida: collaborator
• University of Alabama at Birmingham: collaborator
• The Methodist Hospital Research Institute: collaborator
• University of Virginia: collaborator
• University of Southern California: collaborator

Study Sites (9)

University of Alabama

Birmingham, Alabama, 35205, United States

Location

USC

Los Angeles, California, 90033, United States

Location

UCLA

Santa Monica, California, 90404, United States

Location

University of Florida

Gainesville, Florida, 32611, United States

Location

Gulfcoast Research Institute

Sarasota, Florida, 34232, United States

Location

Phoenix Clinical Research

Tamarac, Florida, 33321, United States

Location

Sinai Hospital of Baltimore

Baltimore, Maryland, 21215, United States

Location

Houston Methodist Research Institute

Houston, Texas, 77030, United States

Location

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

Related Publications (3)

• 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.

  PMID: 39012102 BACKGROUND

• 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.

  PMID: 26833157 BACKGROUND

• 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.

  PMID: 28717038 BACKGROUND

MeSH Terms

Interventions

TRL1068

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

• Sameer Naranje, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

• Stephen Incavo, MD

  The Methodist Hospital Research Institute

  PRINCIPAL INVESTIGATOR

• Ian Duensing, MD

  UVA

  PRINCIPAL INVESTIGATOR

• Daniel Oakes, MD

  University of Southern California

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The study is double-blind and placebo-controlled.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1, Double-Blinded, Single Ascending Dose Study

Study Record Dates

• First Submitted: February 12, 2021
• First Posted: February 21, 2021
• Study Start: February 8, 2021
• Primary Completion: March 13, 2024
• Study Completion: March 13, 2024
• Last Updated: November 21, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)