A Phase 1b, Multicenter, Randomized, Double-blind, Placebo-controlled Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of PMG1015 in Idiopathic Pulmonary Fibrosis (IPF) Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 29
- 试验地点
- 7
- 主要终点
- The incidence of treatment-emergent adverse events (TEAEs)
研究概览
简要总结
This is a phase 1b randomized, double-blind, placebo-controlled, multiple ascending doses (MAD) study of PMG1015 in idiopathic pulmonary fibrosis (IPF) subjects. This study aims to evaluate the safety, tolerability, pharmacokinetics and immunogenicity of PMG1015 after MAD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 40 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of IPF as defined by current American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Association (ALAT) Clinical Practice Guidelines for IPF (2022) (Pathological examination refers to transbronchial lung cryobiopsy or surgical/pleuroscopic lung biopsy);
- •Forced vital capacity percent predicted (FVCpp) ≥45% at screening;
- •Diffusing capacity of the lung for carbon monoxide (DLCO; corrected for haemoglobin) from 30% to 90% of the predicted, inclusive at screening;
- •Subjects not receiving any approved IPF treatment (pirfenidone or nintedanib) within 1 month before enrollment for any reasons
排除标准
- •Patients with instable condition of IPF as assessed by the investigator at screening, and those with acute exacerbation of IPF during screening or within 3 months prior to randomization;
- •Patients who are likely to be lung transplant recipients within 6 months or expected to survive less than 1 year as assessed by the investigator at screening;
- •Patients accompanying with an interstitial lung disease other than IPF;
- •Patients accompanying with other types of respiratory disorders, which may affect the study results as assessed by the investigator;
- •Patients who received vasodilator therapy for pulmonary arterial hypertension (e.g. Bosentan) within 1 month prior to screening;
- •Patients accompanying with other uncontrolled underlying diseases, for which the patient is not considered suitable for the study as assessed by the investigator;
- •Patients who had active tuberculosis within 12 months prior to screening, or clinical symptoms of bacterial, viral, fungal or microbial infections requiring intervention within 4 weeks prior to randomization;
- •Patients who have known allergic reaction to the investigational product or its active pharmaceutical ingredients (APIs), or history of allergic reaction to human, humanized, chimeric, or murine monoclonal antibodies or any substances contained in the excipients;
- •Pregnant or lactating women; female subjects who plan to become pregnant during the study, or patients who are not willing to take contraceptive measures as required by the protocol during the study;
- •Other conditions that preclude the patient from participating in the study as assessed by the investigator.
研究组 & 干预措施
PMG1015
干预措施: PMG1015 (Drug)
Placebo Comparator
干预措施: PMG1015 placebo (Drug)
结局指标
主要结局
The incidence of treatment-emergent adverse events (TEAEs)
时间窗: Approximately 170 days.
An Adverse Event (AE) is any event, side-effect or any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAEs are AEs that occur following the start of treatment.
The severity of treatment-emergent adverse events (TEAEs)
时间窗: Approximately 170 days.
Severity of TEAEs (Grade 1 to 5) will be assessed based on NCI-CTCAE V5.0.
The incidence of serious adverse events (SAEs)
时间窗: Approximately 170 days.
A serious adverse event (SAE) is defined as an AE occurring during any study phase and at any dose of medicinal product that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, or results in congenital anomaly/birth defect.
The severity of serious adverse events (SAEs)
时间窗: Approximately 170 days.
A serious adverse event (SAE) is defined as an AE occurring during any study phase and at any dose of medicinal product that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, or results in congenital anomaly/birth defect.
Assessment of pulmonary function test results-forced vital capacity (FVC)
时间窗: Approximately 170 days.
Pulmonary function test is a test to explore the functional status of human respiratory system with the knowledge of exercise respiratory physiology and modern examination technology. Forced vital capacity (FVC) (mL) will be measured at Visits 1, 8, 14 and 16, to assess the changes in FVC from baseline to post-dose.
Assessment of pulmonary function test results-forced vital capacity percent predicted (FVCpp)
时间窗: Approximately 170 days.
Pulmonary function test is a test to explore the functional status of human respiratory system with the knowledge of exercise respiratory physiology and modern examination technology. Forced vital capacity percent predicted (FVCpp) (%) will be measured at Visits 1, 8, 14 and 16, to assess the changes in FVCpp from baseline to post-dose.
Assessment of pulmonary function test results-diffusing capacity of the lungs for carbon monoxide (DLCO)
时间窗: Approximately 170 days.
Pulmonary function test is a test to explore the functional status of human respiratory system with the knowledge of exercise respiratory physiology and modern examination technology. Diffusing capacity of the lungs for carbon monoxide (DLCO) (mL/min/mmHg) will be measured at Visits 1, 8, 14 and 16, to assess the changes in DLCO from baseline to post-dose.
Assessment of pulmonary function test results-diffusing capacity of the lungs for carbon monoxide percent predicted (DLCOpp)
时间窗: Approximately 170 days.
Pulmonary function test is a test to explore the functional status of human respiratory system with the knowledge of exercise respiratory physiology and modern examination technology. Diffusing capacity of the lungs for carbon monoxide percent predicted (DLCOpp) (DLCO%) will be measured at Visits 1, 8, 14 and 16, to assess the changes in DLCOpp from baseline to post-dose.
Assessment of pulmonary function test results-forced expiratory volume in 1 second (FEV1)
时间窗: Approximately 170 days.
Pulmonary function test is a test to explore the functional status of human respiratory system with the knowledge of exercise respiratory physiology and modern examination technology. Forced expiratory volume in 1 second (FEV1) (L) will be measured at Visits 1, 8, 14 and 16, to assess the changes in FEV1 from baseline to post-dose.
次要结局
- Evaluate the clearance rate (CL) of PMG1015.(Approximately 170 days.)
- Evaluate the area under the serum drug concentration-time curve from time zero to the last quantifiable time point (AUC0-t) of PMG1015.(Approximately 170 days.)
- Evaluate the area under the serum drug concentration-time curve from time zero to infinity (AUC0-∞) of PMG1015.(Approximately 170 days.)
- Evaluate the area under the concentration-time curve from time zero to the end of a dosing interval (AUC0-tau) of PMG1015.(Approximately 170 days.)
- Evaluate the maximum concentration (Cmax) of PMG1015.(Approximately 170 days.)
- Evaluate the time to reach the maximum concentration (Tmax) of PMG1015.(Approximately 170 days.)
- Evaluate the half-life (t1/2) of PMG1015.(Approximately 170 days.)
- Evaluate the distribution volume (Vz) of PMG1015.(Approximately 170 days.)
- Evaluate the elimination rate constant (λz) of PMG1015.(Approximately 170 days.)
- Correlation between the dose and exposure.(Approximately 170 days.)
- Incidence of PMG1015-induced and PMG1015-boosted ADAs.(Approximately 170 days.)