Phase 1 Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of TRL1068 in Subjects With Acute Exacerbation of Chronic Rhinosinusitis
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 12
- 主要终点
- Characterize the pharmacokinetics (PK) of TRL1068 in serum (AUCLAST)
研究概览
简要总结
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.
详细描述
Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with significant morbidity and decreased quality of life. Defects in the epithelial cell barrier, increased exposure to pathogenic and colonized bacteria, and dysregulation of the host immune system are all thought to play prominent roles in disease pathogenesis. Colonization with S. aureus or P. aureus are associated with recalcitrant disease and biofilm formation, making eradication difficult.
Distribution of topical solutions in the unoperated sinuses has been observed to be less than 2% of the total irrigation volume, with almost no penetration in the frontal and sphenoid sinuses. For those patients with mucosal edema from infection and chronic inflammation, distribution is probably significantly less when applied topically. Intravenously administered TRL1068 is expected to achieve effective anti-biofilm levels throughout the sinonasal space for several weeks. TRL1068 is a monoclonal human antibody that rapidly eliminates biofilm at very low concentrations, thus making the targeted bacterial pathogens substantially more sensitive to standard of care antibiotic treatment regimen and greatly accelerating clinical improvement and potential for bacterial eradication.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
TRL1068
all subjects will receive a single intravenous dose of 15 mg/kg of TRL1068 on Day 1
干预措施: TRL1068 (Drug)
结局指标
主要结局
Characterize the pharmacokinetics (PK) of TRL1068 in serum (AUCLAST)
时间窗: 6 weeks
Individual subject TRL1068 AUCLAST in serum will be determined by ELISA and derived PK parameters will be summarized using descriptive statistics.
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: 7 weeks
reported AEs and SAEs will be reviewed
Characterize the pharmacokinetics (PK) of TRL1068 in intrasinal concentrations (Cmin)
时间窗: 6 weeks
Individual subject TRL1068 Cmin intrasinal will be determined by ELISA and derived PK parameters will be summarized using descriptive statistics.
Characterize the pharmacodynamics (PD) of TRL1068 (time to resolution of signs and symptoms of acute exacerbation)
时间窗: 6 weeks
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.
Incidence of abnormal physical exam findings
时间窗: 6 weeks
Clinically-significant abnormal physical exam findings will be reviewed
Incidence of abnormal vital signs (heart rate)
时间窗: 6 weeks
Clinically-significant abnormal heart rates will be reviewed
Characterize the pharmacokinetics (PK) of TRL1068 in serum (Cmax)
时间窗: 6 weeks
Individual subject TRL1068 Cmax in serum will be determined by ELISA and derived PK parameters will be summarized using descriptive statistics.
Incidence of abnormal vital signs (temperature)
时间窗: 6 weeks
Clinically-significant abnormal temperatures will be reviewed
Incidence of abnormal vital signs (blood pressure)
时间窗: 6 weeks
Clinically-significant abnormal blood pressures will be reviewed
Characterize the pharmacokinetics (PK) of TRL1068 in serum (AUCINF)
时间窗: 6 weeks
Individual subject TRL1068 AUCINF in serum will be determined by ELISA and derived PK parameters will be summarized using descriptive statistics.
Characterize the pharmacokinetics (PK) of TRL1068 in intrasinal concentrations (Cmax)
时间窗: 6 weeks
Individual subject TRL1068 Cmax intrasinal will be determined by ELISA and derived PK parameters will be summarized using descriptive statistics.
Characterize the pharmacokinetics (PK) of TRL1068 in intrasinal concentrations (Tmax)
时间窗: 6 weeks
Individual subject TRL1068 Tmax intrasinal will be determined by ELISA and derived PK parameters will be summarized using descriptive statistics.
Assess the immunogenicity of TRL1068 as measured by anti-drug antibodies (ADAs)
时间窗: 6 weeks
Anti-drug antibodies (ADA), i.e. anti-TRL1068 antibodies in serum will determined by electrochemiluminescence assay
Incidence of abnormal serum chemistries and hematology
时间窗: 6 weeks
Clinically-significant abnormal laboratory results will be reviewed
Characterize the pharmacokinetics (PK) of TRL1068 in serum (Cmin)
时间窗: 6 weeks
Individual subject TRL1068 Cmin in serum will be determined by ELISA and derived PK parameters will be summarized using descriptive statistics.
Characterize the pharmacokinetics (PK) of TRL1068 in serum (Tmax)
时间窗: 6 weeks
Individual subject TRL1068 Tmax in serum will be determined by ELISA and derived PK parameters will be summarized using descriptive statistics.
Characterize the pharmacokinetics (PK) of TRL1068 in intrasinal concentrations (AUCINF)
时间窗: 6 weeks
Individual subject TRL1068 AUCINF intrasinal will be determined by ELISA and derived PK parameters will be summarized using descriptive statistics.
Characterize the pharmacodynamics (PD) of TRL1068 (time to resolution of bacterial pathogen infection)
时间窗: 6 weeks
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.
Characterize the pharmacokinetics (PK) of TRL1068 in intrasinal concentrations (AUCLAST)
时间窗: 6 weeks
Individual subject TRL1068 AUCLAST intrasinal will be determined by ELISA and derived PK parameters will be summarized using descriptive statistics.
次要结局
- Assess time to improvement of baseline symptoms of CRS as compared with previous duration of acute exacerbations(7 weeks)
- Assess the incidence of improvement of baseline symptoms of chronic rhinosinusitis (CRS) after intravenous TRL1068(7 weeks)