A Randomized, Double-Blind, Placebo-Controlled Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Inhaled Doses of ICF004 in Healthy Chinese Participants
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 73
- 主要终点
- Number of Participants with Treatment-Emergent Adverse Events (TEAEs)
研究概览
简要总结
The goal of this clinical trial is to learn about the safety of an inhaled study drug called ICF004 in healthy adults. ICF004 is being created to treat progressive lung scarring in the future. It will also learn how the body handles the drug over time.
The main questions it aims to answer are:
What medical problems or side effects do participants have when taking ICF004? How does the body absorb and metabolize ICF004? Researchers will compare ICF004 to a placebo (a look-alike powder that contains no active drug) to see if ICF004 is safe and well-tolerated.
Participants will:
Breathe in a single dose or multiple doses of ICF004 or a placebo using a dry powder inhaler; Stay at or visit the study clinic for checkups and tests; Give blood samples so researchers can measure the amount of drug in their blood.
详细描述
This is a randomized, double-blind, placebo-controlled Phase 1 study of ICF004 dry powder for inhalation in healthy Chinese adult participants. The study will evaluate the safety, tolerability, and plasma pharmacokinetics (PK) of ICF004 after single and multiple inhaled doses.
ICF004 is being developed as a potential treatment for progressive fibrosing interstitial lung disease (PF-ILD). PF-ILD includes interstitial lung diseases in which lung fibrosis continues to worsen. This progression may lead to worsening respiratory symptoms, declining lung function, and increasing fibrosis on high-resolution computed tomography. Current treatment options remain limited.
Preclinical studies suggest that ICF004 may affect signaling pathways involved in fibrosis, including pathways related to transforming growth factor beta 1 (TGF-beta 1). These effects may lower the abnormal deposition of collagen and other extracellular matrix components in the lungs. Administration by inhalation is intended to deliver ICF004 directly to the lungs. This route may achieve higher local lung exposure with a lower administered dose while limiting systemic exposure.
The study consists of a single ascending dose (SAD) part and a multiple ascending dose (MAD) part. Approximately 73 healthy male and female participants will be enrolled. Eligible participants will be 18 to 50 years of age and able to use the dry powder inhalation device correctly.
In each part, participants will be randomly assigned to receive ICF004 or matching placebo. The matching placebo will be administered using the same type of dry powder inhalation device. Participants, investigators, and other applicable study personnel will remain blinded to treatment assignment.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Fully understand the study procedures and methods, volunteer to participate in this study, and sign the written informed consent form.
- •Healthy adult participants, male or female, aged 18 to 50 years (inclusive).
- •Body Mass Index (BMI) ≥ 18 and < 28 kg/m²; body weight ≥ 50.0 kg and < 90.0 kg for males, and ≥ 45.0 kg and < 90.0 kg for females.
- •Medically healthy as determined by the investigator, based on the absence of clinically significant abnormalities in physical examinations, laboratory tests, vital signs, chest X-ray, and electrocardiogram (ECG).
- •Able to use the inhalation device correctly and effectively.
- •Agree to use effective contraceptive measures throughout the study period. Female participants of childbearing potential must agree to use effective contraception from the screening period until 6 months after the last dose. During this period, female participants must agree to have no plans for pregnancy or egg donation/harvesting; male participants must agree to have no plans to father a child or donate sperm. Their male or female partners of childbearing potential must also agree to use effective contraceptive measures during this period.
排除标准
- •History of any clinically significant disease (including past and current history), including but not limited to respiratory, cardiovascular, gastrointestinal, hematological, endocrine, immunological, dermatological, malignant tumor, neuropsychiatric, ear/nose/throat (ENT), or metabolic diseases; or any other condition that, in the opinion of the investigator (or sub-investigator), makes the participant unsuitable for the study.
- •Major surgery within 6 months prior to dosing, planned surgery during the study, or previous surgery that may significantly affect the pharmacokinetics or safety evaluation of the study drug.
- •Current oral diseases that may affect the study, as judged by the investigator (e.g., oropharyngeal candidiasis, oral ulcers, oral mucosal lesions).
- •Fever (body temperature > 37.5°C) or symptomatic respiratory infection within 1 month prior to dosing; any infection requiring systemic antibiotics or antivirals within 3 months prior to screening; or a history of recurrent infections.
- •Positive test results for Human Immunodeficiency Virus (HIV), Hepatitis B surface antigen (HBsAg), Treponema pallidum (syphilis) antibody, or Hepatitis C Virus (HCV) antibody.
- •Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), or total bilirubin exceeding the upper limit of normal (ULN) at the screening or baseline visit.
- •Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) < 80% of the predicted value, or FEV1/FVC < 0.7, or arterial oxygen saturation < 95% at the screening or baseline visit.
- •Smoking (including e-cigarettes) within 6 months prior to dosing, or a positive smoking (nicotine/cotinine) test.
- •History of drug abuse within 3 months prior to screening, or a positive urine drug screen.
- •Participation in any drug or medical device clinical trial within 3 months prior to screening.
- •Blood donation or blood loss ≥ 400 mL within 3 months prior to dosing.
- •Difficulty in venous blood sampling, intolerance to venipuncture, or a history of needle or blood phobia (vasovagal syncope).
- •Known allergy to the study drug or any of its ingredients.
- •Female participants who are pregnant or lactating, or who plan to become pregnant from the time of the study through 6 months after the last dose.
- •Any condition that, in the opinion of the investigator, makes the participant unsuitable for participation in the study.
结局指标
主要结局
Number of Participants with Treatment-Emergent Adverse Events (TEAEs)
时间窗: Day 1 through Day 7 for SAD and Day 1 through Day 14 for MAD
A treatment-emergent adverse event (TEAE) is an adverse event that begins or worsens after the first dose of ICF004 or placebo. Safety assessments include local irritation symptoms, clinical laboratory tests, 12-lead electrocardiograms, pulmonary function tests, vital signs, and physical examinations. Clinically significant abnormal findings may be recorded as adverse events, as determined by the investigator.
次要结局
- Cmax: Maximum Observed Plasma Concentration After a Single Dose(Predose; 5, 10, 20, 30, and 45 minutes; and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose.)
- Tmax: Time to Maximum Observed Plasma Concentration After a Single Dose(Predose; 5, 10, 20, 30, and 45 minutes; and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose.)
- AUC0-t: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Measurable Concentration After a Single Dose(Predose; 5, 10, 20, 30, and 45 minutes; and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose.)
- AUC0-♾️: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity After a Single Dose(Predose; 5, 10, 20, 30, and 45 minutes; and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose.)
- t1/2z: Terminal Elimination Half-Life After a Single Dose(Predose; 5, 10, 20, 30, and 45 minutes; and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose.)
- λz: Terminal Elimination Rate Constant After a Single Dose(Predose; 5, 10, 20, 30, and 45 minutes; and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose.)
- CLz/F: Apparent Total Clearance After a Single Dose(Predose; 5, 10, 20, 30, and 45 minutes; and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose.)
- Vd/F: Apparent Volume of Distribution During the Terminal Phase After a Single Dose(Predose; 5, 10, 20, 30, and 45 minutes; and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose.)
- MRT: Mean Residence Time After a Single Dose(Predose; 5, 10, 20, 30, and 45 minutes; and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose.)
- AUCE_%Extrap: Percentage of AUC0-♾️ Extrapolated From the Last Measurable Concentration to Infinity After a Single Dose(Predose; 5, 10, 20, 30, and 45 minutes; and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose.)
- Cmax: Maximum Observed Plasma Concentration After the First Dose(At 0 hour (within 1 hour predose); 5, 10, 20, 30, and 45 minutes; and 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours post-dose; additionally at 24 hours post-dose for the once-daily cohorts.)
- Tmax: Time to Maximum Observed Plasma Concentration After the First Dose(At 0 hour (within 1 hour predose); 5, 10, 20, 30, and 45 minutes; and 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours post-dose; additionally at 24 hours post-dose for the once-daily cohorts.)
- AUC0-t: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Measurable Concentration After the First Dose(At 0 hour (within 1 hour predose); 5, 10, 20, 30, and 45 minutes; and 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours post-dose; additionally at 24 hours post-dose for the once-daily cohorts.)
- Ctrough,ss: Trough Plasma Concentration at Steady State(At 0 hour (within 1 hour before the morning dose) on Days 3, 4, 5, 6, and 7.)
- Cmax,ss: Maximum Observed Plasma Concentration After the Last Dose(At 0 hour on Day 7 (within 1 hour predose); 5, 10, 20, 30, and 45 minutes; and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours after the last dose.)
- Tmax,ss: Time to Maximum Observed Plasma Concentration After the Last Dose(At 0 hour on Day 7 (within 1 hour predose); 5, 10, 20, 30, and 45 minutes; and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours after the last dose.)
- Cav,ss: Average Plasma Concentration at Steady State(At 0 hour on Day 7 (within 1 hour predose); 5, 10, 20, 30, and 45 minutes; and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours after the last dose.)
- AUC0-t,ss: Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Measurable Concentration After the Last Dose(At 0 hour on Day 7 (within 1 hour predose); 5, 10, 20, 30, and 45 minutes; and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours after the last dose.)
- AUC0-tau,ss: Area Under the Plasma Concentration-Time Curve Over a Dosing Interval at Steady State(At 0 hour on Day 7 (within 1 hour predose) through 24 hours after the last dose for the once-daily cohorts, and through 12 hours after the last dose for the twice-daily cohorts.)
- AUC0-♾️: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity After the Last Dose(At 0 hour on Day 7 (within 1 hour predose); 5, 10, 20, 30, and 45 minutes; and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours after the last dose.)
- t1/2: Terminal Elimination Half-Life After the Last Dose(At 0 hour on Day 7 (within 1 hour predose); 5, 10, 20, 30, and 45 minutes; and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours after the last dose.)
- λz: Terminal Elimination Rate Constant After the Last Dose(At 0 hour on Day 7 (within 1 hour predose); 5, 10, 20, 30, and 45 minutes; and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours after the last dose.)
- CLss/F: Apparent Clearance at Steady State(At 0 hour on Day 7 (within 1 hour predose); 5, 10, 20, 30, and 45 minutes; and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours after the last dose.)
- Vd/F: Apparent Volume of Distribution During the Terminal Phase After the Last Dose(At 0 hour on Day 7 (within 1 hour predose); 5, 10, 20, 30, and 45 minutes; and 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours after the last dose.)
- DF: Degree of Fluctuation at Steady State(At 0 hour on Day 7 (within 1 hour predose) through 24 hours after the last dose for the once-daily cohorts, and through 12 hours after the last dose for the twice-daily cohorts.)
- Swing: Peak-to-Trough Fluctuation at Steady State(At 0 hour on Day 7 (within 1 hour predose) through 24 hours after the last dose for the once-daily cohorts, and through 12 hours after the last dose for the twice-daily cohorts.)
- Rcmax: Accumulation Ratio Based on Maximum Plasma Concentration(From the first dose on Day 1 through 24 hours after the last dose on Day 7.)
- RAUC: Accumulation Ratio Based on Area Under the Plasma Concentration-Time Curve(From the first dose on Day 1 through 24 hours after the last dose on Day 7.)