Study to Evaluate Safety and Activity of TRL1068 in Chronic Rhinosinusitis

NCT05355207 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: TRL1068-104
• Study Type: interventional
• Target: 12
• Locations: 0 countries
• Sites: N/A

Brief Summary

TRL1068 is expected to eliminate the pathogen-protecting biofilm in Chronic Rhinosinusitis, thus making these bacteria substantially more susceptible to established antibiotic treatment regimens. This initial study is to assess overall safety and pharmacokinetics (PK) of TRL1068. The goal of the development program is to demonstrate effectiveness of TRL1068 in difficult to treat bacterial infections such as in CRS.

Conditions

Chronic Rhinosinusitis With Nasal Polyps

Keywords

biofilm; antibiotic-resistant infections

Outcome Measures

Primary Outcomes (19)

• Incidence of abnormal physical exam findings

  Clinically-significant abnormal physical exam findings will be reviewed

  6 weeks

• Incidence of abnormal serum chemistries and hematology

  Clinically-significant abnormal laboratory results will be reviewed

  6 weeks

• Incidence of abnormal vital signs (temperature)

  Clinically-significant abnormal temperatures will be reviewed

  6 weeks

• Incidence of abnormal vital signs (blood pressure)

  Clinically-significant abnormal blood pressures will be reviewed

  6 weeks

• Incidence of abnormal vital signs (heart rate)

  Clinically-significant abnormal heart rates will be reviewed

  6 weeks

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

  reported AEs and SAEs will be reviewed

  7 weeks

• Characterize the pharmacokinetics (PK) of TRL1068 in serum (Cmax)

  Individual subject TRL1068 Cmax in serum will be determined by ELISA and derived PK parameters will be summarized using descriptive statistics.

  6 weeks

• Characterize the pharmacokinetics (PK) of TRL1068 in serum (Cmin)

  Individual subject TRL1068 Cmin in serum will be determined by ELISA and derived PK parameters will be summarized using descriptive statistics.

  6 weeks

• Characterize the pharmacokinetics (PK) of TRL1068 in serum (Tmax)

  Individual subject TRL1068 Tmax in serum will be determined by ELISA and derived PK parameters will be summarized using descriptive statistics.

  6 weeks

• Characterize the pharmacokinetics (PK) of TRL1068 in serum (AUCLAST)

  Individual subject TRL1068 AUCLAST in serum will be determined by ELISA and derived PK parameters will be summarized using descriptive statistics.

  6 weeks

• Characterize the pharmacokinetics (PK) of TRL1068 in serum (AUCINF)

  Individual subject TRL1068 AUCINF in serum will be determined by ELISA and derived PK parameters will be summarized using descriptive statistics.

  6 weeks

• Characterize the pharmacokinetics (PK) of TRL1068 in intrasinal concentrations (Cmax)

  Individual subject TRL1068 Cmax intrasinal will be determined by ELISA and derived PK parameters will be summarized using descriptive statistics.

  6 weeks

• Characterize the pharmacokinetics (PK) of TRL1068 in intrasinal concentrations (Cmin)

  Individual subject TRL1068 Cmin intrasinal will be determined by ELISA and derived PK parameters will be summarized using descriptive statistics.

  6 weeks

• Characterize the pharmacokinetics (PK) of TRL1068 in intrasinal concentrations (Tmax)

  Individual subject TRL1068 Tmax intrasinal will be determined by ELISA and derived PK parameters will be summarized using descriptive statistics.

  6 weeks

• Characterize the pharmacokinetics (PK) of TRL1068 in intrasinal concentrations (AUCLAST)

  Individual subject TRL1068 AUCLAST intrasinal will be determined by ELISA and derived PK parameters will be summarized using descriptive statistics.

  6 weeks

• Characterize the pharmacokinetics (PK) of TRL1068 in intrasinal concentrations (AUCINF)

  Individual subject TRL1068 AUCINF intrasinal will be determined by ELISA and derived PK parameters will be summarized using descriptive statistics.

  6 weeks

• Characterize the pharmacodynamics (PD) of TRL1068 (time to resolution of bacterial pathogen infection)

  Cultures will be tested for bacterial pathogen presence by bacterial culture and/or PCR assessment. Time to resolution of bacterial pathogen infection is defined as the number of days from start of current acute exacerbation to the day when testing by bacterial culture and/or PCR assessment are reported as negative. Descriptive statistics will be performed including mean, median and confidence interval.

  6 weeks

• Characterize the pharmacodynamics (PD) of TRL1068 (time to resolution of signs and symptoms of acute exacerbation)

  Patients will be evaluated for signs and symptoms of acute exacerbation using SNOT-22 scoring. Time to resolution of signs and symptoms of acute exacerbation is defined as the day when the SNOT-22 score is back to pre-acute exacerbation score.

  6 weeks

• 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

  6 weeks

Secondary Outcomes (2)

• Assess the incidence of improvement of baseline symptoms of chronic rhinosinusitis (CRS) after intravenous TRL1068

  7 weeks

• Assess time to improvement of baseline symptoms of CRS as compared with previous duration of acute exacerbations

  7 weeks

Other Outcomes (1)

• Assess the effects of treatment on the intrasinal microbiome

  6 weeks

Study Arms (1)

TRL1068

EXPERIMENTAL

all subjects will receive a single intravenous dose of 15 mg/kg of TRL1068 on Day 1

Drug: TRL1068

Interventions

TRL1068 DRUG

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

TRL1068

Eligibility Criteria

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

You may qualify if:

• Age 18 to 85 years, inclusive
• Diagnosis of chronic rhinosinusitis with:
• Acute exacerbation of CRSwNP with increased sinonasal discharge OR
• Acute exacerbation post-functional endoscopic sinus surgery (FESS) with increased sinonasal discharge AND
• Sinonasal culture positive for SA or PA without concomitant fungal infection in culture or PCR
• Symptoms and culture results justify initiation of topical and/or systemic antibiotic treatment
• 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 that may include, but is not limited to, abstinence, sex only with persons of the same sex, monogamous relationship with vasectomized partner, vasectomy, hysterectomy, bilateral tubal ligation, licensed hormonal methods, intrauterine device (IUD), or use of spermicide combined with a barrier method (e.g., condom, diaphragm) for 28 days before receiving the investigational product (IP) and through Day 50.

You may not qualify if:

• Active malignancy, or history of malignancy or chemotherapy within the past 2 years other than history of localized or surgical removal of focal skin cancer, or cervical cancer in situ treated successfully in the past by local treatment (including but not limited to cryotherapy or laser therapy) or by hysterectomy
• Any chronic or acute bacterial infection other than acute exacerbation of CRS
• Concomitant intrasinal culture or 16S PCR indicative of concomitant fungal infection
• Allergic fungal rhinosinusitis, characterized by elevated antifungal IgE and eosinophilic mucus
• Receiving or recently received another investigational drug (within 30 days of Day 1, or 5 half-lives of the investigational drug, whichever is longer)
• Received a COVID-19 vaccine or booster within 14 days of planned Day 1 or planned COVID-19 vaccination within 14 days after Day 1
• Positive serum test for pregnancy, pregnant, or nursing women
• 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

Sponsors & Collaborators

• Trellis Bioscience LLC: lead

Related Publications (2)

• 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

Central Study Contacts

Anton (Tony) Leighton, MD

CONTACT

650-838-1400; Clinicalstudies@trellisbio.com

Adriane Kisch-Hancock

CONTACT

650-838-1400; akisch-hancock@trellisbio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: single group, all subjects will receive 15 mg/kg of TRL1068 on Day 1

Study Record Dates

• First Submitted: April 18, 2022
• First Posted: May 2, 2022
• Study Start: January 1, 2024
• Primary Completion: January 1, 2025
• Study Completion: January 1, 2025
• Last Updated: April 12, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Before trial recruitment is complete on Protocols.io (https://www.protocols.io/)
• Access Criteria: available