Ignite Creation Date:
2025-12-24 @ 3:05 PM
Ignite Modification Date:
2026-01-01 @ 5:37 PM
Study NCT ID:
NCT04763759
Status:
COMPLETED
Last Update Posted:
2024-11-21
First Post:
2021-02-12
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Study to Evaluate Safety and Activity of TRL1068 in Prosthetic Joint Infections
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'C000627168', 'term': 'TRL1068'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR'], 'maskingDescription': 'The study is double-blind and placebo-controlled.'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Phase 1, Double-Blinded, Single Ascending Dose Study'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 15}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2021-02-08', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-11', 'completionDateStruct': {'date': '2024-03-13', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2024-11-18', 'studyFirstSubmitDate': '2021-02-12', 'studyFirstSubmitQcDate': '2021-02-18', 'lastUpdatePostDateStruct': {'date': '2024-11-21', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2021-02-21', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2024-03-13', 'type': 'ACTUAL'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Exploratory outcome measure to determine CFUs', 'timeFrame': '12 weeks', '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.'}, {'measure': 'Exploratory outcome measure to determine inflammation (CRP)', 'timeFrame': '16 weeks', 'description': 'The mean levels of C reactive protein (CRP) from placebo and TRL1068 treated groups will be compared.'}, {'measure': 'Exploratory outcome measure to determine inflammation (ESR)', 'timeFrame': '16 weeks', 'description': 'The mean levels of erythrocyte sedimentation rate (ESR) from placebo and TRL1068 treated groups will be compared.'}, {'measure': 'Exploratory outcome measure to determine inflammation (IL-6)', 'timeFrame': '16 weeks', 'description': 'The mean levels of Interleukin-6 (IL-6) from placebo and TRL1068 treated groups will be compared.'}, {'measure': 'Exploratory outcome measure to determine inflammation (IL-10)', 'timeFrame': '16 weeks', 'description': 'The mean levels of Interleukin-10 (IL-10) from placebo and TRL1068 treated groups will be compared.'}, {'measure': 'Exploratory outcome measure to determine infection in synovial fluid', 'timeFrame': '1 week', 'description': 'The number of subjects with CFUs/mL ≥ 1 from the synovial fluid from placebo and TRL1068 treated groups will be compared.'}, {'measure': 'Exploratory outcome measure inflammation in the synovial fluid', 'timeFrame': '1 week', 'description': 'The mean synovial fluid total leukocyte cell counts of the consolidated placebo and TRL1068 treated groups will be compared.'}, {'measure': 'Exploratory outcome measure to assess quality of life', 'timeFrame': '24 weeks', '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.'}], 'primaryOutcomes': [{'measure': 'Incidence of Abnormal Physical Examination Findings', 'timeFrame': '16 weeks', 'description': 'clinically significant abnormal physical exam findings will be reviewed'}, {'measure': 'Incidence of Abnormal Serum Chemistries and Hematology', 'timeFrame': '16 weeks', 'description': 'clinically significant abnormal laboratory results will be reviewed'}, {'measure': 'Incidence of Abnormal Vital Signs (Temperature)', 'timeFrame': '16 weeks', 'description': 'clinically significant abnormal temperatures will be reviewed'}, {'measure': 'Incidence of Abnormal Vital Signs (Blood Pressure)', 'timeFrame': '16 weeks', 'description': 'clinically significant abnormal blood pressures will be reviewed'}, {'measure': 'Incidence of Abnormal Vital Signs (Heart Rate)', 'timeFrame': '16 weeks', 'description': 'clinically significant abnormal heart rates will be reviewed'}, {'measure': 'Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)', 'timeFrame': '24 weeks', 'description': 'mortality and any other reported AEs and SAEs will be reviewed'}], 'secondaryOutcomes': [{'measure': 'Characterize the pharmacokinetics (PK) of a single IV infusion of TRL1068', 'timeFrame': '16 weeks', 'description': 'Serum and synovial concentrations of TRL1068 will be determined by ELISA'}, {'measure': 'Measure TRL1068 levels in synovial fluid on Day 8 and compare with plasma PK', 'timeFrame': '1 week', 'description': 'Serum and synovial concentrations of TRL1068 will be determined by ELISA'}, {'measure': 'Assess the pharmacodynamics (PD) of TRL1068 (Colony Forming Units (CFUs) prosthesis)', 'timeFrame': '1 week', 'description': 'Number of CFUs from sonicated prosthetic device'}, {'measure': 'Assess the pharmacodynamics (PD) of TRL1068 (CFUs spacer)', 'timeFrame': '12 weeks', 'description': 'Number of CFUs from sonicated orthopedic spacer'}, {'measure': 'Assess the pharmacodynamics (PD) of TRL1068 (CRP)', 'timeFrame': '16 weeks', 'description': 'Inflammatory biomarker CRP'}, {'measure': 'Assess the pharmacodynamics (PD) of TRL1068 (ESR)', 'timeFrame': '16 weeks', 'description': 'Inflammatory biomarker ESR'}, {'measure': 'Assess the pharmacodynamics (PD) of TRL1068 (IL-6)', 'timeFrame': '16 weeks', 'description': 'Inflammatory biomarker IL-6'}, {'measure': 'Assess the pharmacodynamics (PD) of TRL1068 (IL-10)', 'timeFrame': '16 weeks', 'description': 'Inflammatory biomarker IL-10'}, {'measure': 'Assess the pharmacodynamics (PD) of TRL1068 (reinfection)', 'timeFrame': '24 weeks', 'description': 'Assessment for reinfection including need for further surgical interventions and overall outcome'}, {'measure': 'Assess the immunogenicity of TRL1068 as measured by anti-drug antibodies (ADAs)', 'timeFrame': '16 weeks', 'description': 'Anti-drug antibodies (ADA), i.e. anti-TRL1068 antibodies in serum will determined by electrochemiluminescence assay.'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['biofilm', 'antibiotic-resistant infections'], 'conditions': ['Prosthetic Joint Infection']}, 'referencesModule': {'references': [{'pmid': '39012102', 'type': 'BACKGROUND', 'citation': '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': '26833157', 'type': 'BACKGROUND', '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.'}, {'pmid': '28717038', 'type': 'BACKGROUND', '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.'}]}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': '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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '85 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Diagnosis of PJI of the knee or hip\n* Identified pathogen(s) must be susceptible to antibiotic regimen\n* Planned/scheduled for primary two-stage exchange arthroplasty\n* BMI \\< 40 kg/m²\n* Willing and able to provide written informed consent\n* Willing to perform and comply with all study procedures including attending clinic visits as scheduled.\n* Men and women of child bearing potential (WOCBP) must be willing to practice a highly effective method of contraception\n\nExclusion Criteria:\n\n* Evidence of active infection other than bacterial PJI of the knee or hip\n* Inability to receive or intolerant to pathogen-appropriate systemic or oral antibiotic therapy\n* Chronic obstructive pulmonary disease (COPD)\n* Child-Pugh score \\> 6\n* Congestive heart failure\n* Immunocompromised individuals, including those receiving immunosuppressive doses of corticosteroids\n* Active malignancy, or history of malignancy or chemotherapy within the past 2 years\n* Active or history of autoimmune disease\n* Uncontrolled diabetes, defined as hemoglobin A1c \\> 7.4%\n* Clinically significant abnormality on electrocardiogram (ECG) that would preclude subject from undergoing two-stage exchange arthroplasty\n* Clinically significant serum chemistry or hematology abnormalities\n* Any acute illness within 14 days of Day 1 that could confound the evaluation of safety evaluation\n* Known or suspected intolerance or hypersensitivity to any biologic medication\n* Received a therapeutic antibody or biologic within the 6 months prior to Screening\n* Positive serum test for pregnancy, pregnant, or nursing women\n* Positive reverse transcription polymerase chain reaction (RT -PCR) or alternative (antigen) test for acute respiratory syndrome coronavirus 2\n* 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\n* 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"}, 'identificationModule': {'nctId': 'NCT04763759', 'briefTitle': 'Study to Evaluate Safety and Activity of TRL1068 in Prosthetic Joint Infections', 'organization': {'class': 'INDUSTRY', 'fullName': 'Trellis Bioscience LLC'}, 'officialTitle': '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', 'orgStudyIdInfo': {'id': 'TRL1068-101'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Dose Level 1- 6mg/kg', 'description': 'Randomized 3:1 (TRL1068:placebo) via IV infusion', 'interventionNames': ['Drug: TRL1068, a human monoclonal antibody']}, {'type': 'EXPERIMENTAL', 'label': 'Dose Level 2- 15mg/kg', 'description': 'Randomized 5:2 (TRL1068:placebo) via IV infusion', 'interventionNames': ['Drug: TRL1068, a human monoclonal antibody']}, {'type': 'EXPERIMENTAL', 'label': 'Dose Level 3- 30 mg/kg', 'description': 'Randomized 5:2 (TRL1068:placebo) via IV infusion', 'interventionNames': ['Drug: TRL1068, a human monoclonal antibody']}], 'interventions': [{'name': 'TRL1068, a human monoclonal antibody', 'type': 'DRUG', 'description': 'A human IgG1κ (G1m1,17 (z,a); Km3 allotype) monoclonal antibody', 'armGroupLabels': ['Dose Level 1- 6mg/kg', 'Dose Level 2- 15mg/kg', 'Dose Level 3- 30 mg/kg']}]}, 'contactsLocationsModule': {'locations': [{'zip': '35205', 'city': 'Birmingham', 'state': 'Alabama', 'country': 'United States', 'facility': 'University of Alabama', 'geoPoint': {'lat': 33.52066, 'lon': -86.80249}}, {'zip': '90033', 'city': 'Los Angeles', 'state': 'California', 'country': 'United States', 'facility': 'USC', 'geoPoint': {'lat': 34.05223, 'lon': -118.24368}}, {'zip': '90404', 'city': 'Santa Monica', 'state': 'California', 'country': 'United States', 'facility': 'UCLA', 'geoPoint': {'lat': 34.01949, 'lon': -118.49138}}, {'zip': '32611', 'city': 'Gainesville', 'state': 'Florida', 'country': 'United States', 'facility': 'University of Florida', 'geoPoint': {'lat': 29.65163, 'lon': -82.32483}}, {'zip': '34232', 'city': 'Sarasota', 'state': 'Florida', 'country': 'United States', 'facility': 'Gulfcoast Research Institute', 'geoPoint': {'lat': 27.33643, 'lon': -82.53065}}, {'zip': '33321', 'city': 'Tamarac', 'state': 'Florida', 'country': 'United States', 'facility': 'Phoenix Clinical Research', 'geoPoint': {'lat': 26.21286, 'lon': -80.24977}}, {'zip': '21215', 'city': 'Baltimore', 'state': 'Maryland', 'country': 'United States', 'facility': 'Sinai Hospital of Baltimore', 'geoPoint': {'lat': 39.29038, 'lon': -76.61219}}, {'zip': '77030', 'city': 'Houston', 'state': 'Texas', 'country': 'United States', 'facility': 'Houston Methodist Research Institute', 'geoPoint': {'lat': 29.76328, 'lon': -95.36327}}, {'zip': '22903', 'city': 'Charlottesville', 'state': 'Virginia', 'country': 'United States', 'facility': 'University of Virginia', 'geoPoint': {'lat': 38.02931, 'lon': -78.47668}}], 'overallOfficials': [{'name': 'Nicholas Bernthal, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of California, Los Angeles'}, {'name': 'Janet Conway, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Sinai Hospital of Baltimore'}, {'name': 'Edward Stolarski, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Gulfcoast Research Institute'}, {'name': 'Richard Berkowitz, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Phoenix Clinical Research'}, {'name': 'Luis Pulido, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Florida'}, {'name': 'Sameer Naranje, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Alabama at Birmingham'}, {'name': 'Stephen Incavo, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'The Methodist Hospital Research Institute'}, {'name': 'Ian Duensing, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'UVA'}, {'name': 'Daniel Oakes, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Southern California'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO', 'description': 'The study results have been published.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Trellis Bioscience LLC', 'class': 'INDUSTRY'}, 'collaborators': [{'name': 'University of California, Los Angeles', 'class': 'OTHER'}, {'name': 'Biomedical Advanced Research and Development Authority', 'class': 'FED'}, {'name': 'Wellcome Trust', 'class': 'OTHER'}, {'name': 'Sinai Hospital of Baltimore', 'class': 'OTHER'}, {'name': 'Gulfcoast Research Institute', 'class': 'UNKNOWN'}, {'name': 'Phoenix Clinical Research', 'class': 'OTHER'}, {'name': 'University of Florida', 'class': 'OTHER'}, {'name': 'University of Alabama at Birmingham', 'class': 'OTHER'}, {'name': 'The Methodist Hospital Research Institute', 'class': 'OTHER'}, {'name': 'University of Virginia', 'class': 'OTHER'}, {'name': 'University of Southern California', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR'}}}}