NCT05537025已完成1 期
A Phase 1/2a Study Evaluating the Effects of ARO-MMP7 Inhalation Solution in Healthy Subjects and Patients With Idiopathic Pulmonary Fibrosis
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 105
- 试验地点
- 24
- 主要终点
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Over Time
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of ARO-MMP7 in normal healthy volunteers (NHVs) and in participants with idiopathic pulmonary fibrosis (IPF). The study will initiate with NHVs receiving single ascending doses of ARO-MMP7. Following evaluation of safety and pharmacodynamic (PD) data, participants will receive multiple doses of ARO-MMP7.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Normal pulmonary function tests at Screening
- •Normal electrocardiogram (ECG) at Screening
- •Non-smoking
- •Female participants cannot be pregnant or lactating
- •Male and female participants of childbearing potential must agree to use highly effective contraception and must not donate eggs/sperm during the study and for at least 90 days following end of study or last dose of study drug, whichever is later.
- •Inclusion Criteria (IPF Participants):
- •Age ≥ 45 years at Screening
- •Clinical diagnosis consistent with IPF based upon established criteria confirmed by review of high-resolution computed tomography (HRCT) and surgical lung biopsy findings (if available)
- •Safely able to undergo bronchoscopy
- •Stable IPF disease at Screening with minimum life expectancy of ≥ 12 months from Screening
- •Female participants cannot be pregnant or lactating
- •Male and female participants of childbearing potential must agree to use highly effective contraception and must not donate eggs/sperm during the study and for at least 90 days following end of study or last dose of study drug, whichever is later.
排除标准
- •Acute lower respiratory infection within 30 days prior to first dose or acute upper respiratory infection within 7 days prior to first dose
- •Positive coronavirus disease (COVID-19) test during Screening window
- •Any history of chronic pulmonary disease or anaphylaxis
- •Human immunodeficiency virus (HIV) infection, seropositive for hepatitis B virus (HBV), seropositive for hepatitis C virus (HCV)
- •Uncontrolled hypertension
- •History of significant cardiac disease
- •History of major surgery within 12 weeks prior to first dose
- •Unwilling to limit alcohol consumption to within moderate limits for the duration of the study
- •Use of illicit drugs
- •Use of an investigational agent or device within 30 days prior to first dose
- •Exclusion Criteria (IPF Participants):
- •Interstitial lung disease (ILD) associated with known primary cause
- •Positive COVID-19 test during Screening window
- •IPF exacerbation within 6 weeks prior to first dose
- •Lower respiratory tract infection requiring antibiotics or antivirals within 30 days prior to first dose
- •Smoking cigarettes or e-cigarettes within 3 months prior to first dose
- •Use of systemic corticosteroid therapy within 30 days prior to first dose
- •Initiation or cessation of antifibrotic therapy or change of antifibrotic dose regimen within 10 weeks prior to first dose
- •Any history of lung transplant or plan to undergo transplant during the course of the study
- •Any concomitant pulmonary disease that could interfere with the evaluation of the study drug or interpretation of patient safety or study results
- •HIV infection, seropositive for HBV, seropositive for HCV
- •Uncontrolled hypertension
- •History of significant cardiac disease
- •History of major surgery within 12 weeks prior to first dose
- •Unwilling to limit alcohol consumption to within moderate limits for the duration of the study
- •Use of illicit drugs
- •Use of an investigational agent or device within 30 days prior to first dose
- •Note: additional inclusion/exclusion criteria may apply per protocol
研究组 & 干预措施
ARO-MMP7
Experimental
single or multiple doses of ARO-MMP7 by inhalation of nebulized solution
干预措施: ARO-MMP7 Inhalation Solution (Drug)
Placebo
Placebo Comparator
single or multiple doses of placebo by inhalation of nebulized solution
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Over Time
时间窗: From first dose of study drug through the end of study (EOS; up to 85 days, or until sputum MMP7 protein concentration is ≥ 70% of the baseline value, whichever is later)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
时间窗: Day 1 up to Day 85
An adverse event (AE) was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to study drug. TEAEs were defined as AEs with onset after administration of the study drug, or when a pre-existing medical condition increases in severity or frequency after study drug administration. A summary of all Serious Adverse Events (SAEs) and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
次要结局
- Change From Baseline Over Time in Forced Vital Capacity (FVC)(Baseline through EOS (up to 85 days, or until serum MMP7 protein concentration is ≥ 70% of the baseline value, whichever is later))
- PK of ARO-MMP7: Renal Clearance (CLr) in NHVs(single dose phase: up to 168 hours post-dose; multiple dose phase: up to 6 hours post-dose on Days 1 and 15 or 29, 24 hours post-dose on Days 2 and 30)
- Change From Baseline Over Time in Forced Expiratory Volume (FEV1)(Baseline through EOS (up to 85 days, or until serum MMP7 protein concentration is ≥ 70% of the baseline value, whichever is later))
- Change From Baseline Over Time in Diffusing Capacity for Carbon Monoxide (DLCO)(Baseline through EOS (up to 85 days, or until serum MMP7 protein concentration is ≥ 70% of the baseline value, whichever is later))
- PK of ARO-MMP7: Maximum Observed Plasma Concentration (Cmax)(single dose phase: up to 168 hours post-dose; multiple dose phase: up to 6 hours post-dose on Days 1 and 15 or 29, 24 hours post-dose on Days 2 and 30, and (IPF only) Days 8, 22, and 36)
- PK of ARO-MMP7: Area Under the Plasma Concentration versus Time Curve from Zero to 24 Hours (AUC0-24)(single dose phase: up to 168 hours post-dose; multiple dose phase: up to 6 hours post-dose on Days 1 and 15 or 29, 24 hours post-dose on Days 2 and 30, and (IPF only) Days 8, 22, and 36)
- PK of ARO-MMP7: Terminal Elimination Half-Life (t1/2)(single dose phase: up to 168 hours post-dose; multiple dose phase: up to 6 hours post-dose on Days 1 and 15 or 29, 24 hours post-dose on Days 2 and 30, and (IPF only) Days 8, 22, and 36)
- PK of ARO-MMP7: Apparent Systemic Clearance (CL/F)(single dose phase: up to 168 hours post-dose; multiple dose phase: up to 6 hours post-dose on Days 1 and 15 or 29, 24 hours post-dose on Days 2 and 30, and (IPF only) Days 8, 22, and 36)
- PK of ARO-MMP7: Area Under the Plasma Concentration versus Time Curve from Zero to the Last Quantifiable Plasma Concentration (AUClast)(single dose phase: up to 168 hours post-dose; multiple dose phase: up to 6 hours post-dose on Days 1 and 15 or 29, 24 hours post-dose on Days 2 and 30, and (IPF only) Days 8, 22, and 36)
- PK of ARO-MMP7: Area Under the Plasma Concentration versus Time Curve from Zero to Infinity (AUCinf)(single dose phase: up to 168 hours post-dose; multiple dose phase: up to 6 hours post-dose on Days 1 and 15 or 29, 24 hours post-dose on Days 2 and 30, and (IPF only) Days 8, 22, and 36)
- PK of ARO-MMP7: Apparent Terminal Phase Volume of Distribution (VZ/F)(single dose phase: up to 168 hours post-dose; multiple dose phase: up to 6 hours post-dose on Days 1 and 15 or 29, 24 hours post-dose on Days 2 and 30, and (IPF only) Days 8, 22, and 36)
- PK of ARO-MMP7: Recovery of Unchanged Drug in Urine Over 0 to 24 Hours (Amount excreted; Ae) in NHVs(single dose phase: up to 168 hours post-dose; multiple dose phase: up to 6 hours post-dose on Days 1 and 15 or 29, 24 hours post-dose on Days 2 and 30)
- PK of ARO-MMP7: Percentage of Administered Drug Recovered in Urine Over 0 to 24 Hours in NHVs(single dose phase: up to 168 hours post-dose; multiple dose phase: up to 6 hours post-dose on Days 1 and 15 or 29, 24 hours post-dose on Days 2 and 30)
- IPF Cohorts: Tmax of ARO-MMP7(Pre-dose up to 6 hours post-dose on Days 1, 15, and 29)
- SAD Cohorts: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24) of ARO-MMP7(Pre-dose up to 24 hours post-dose (Day 2))
- MAD Cohorts: AUC0-24 of ARO-MMP7(Pre-dose up to 24 hours post-dose on Days 1, 15, and 29)
- IPF Cohorts: AUC0-24 of ARO-MMP7(Pre-dose up to 24 hours post-dose on Days 1, 15, and 29)
- SAD Cohorts: Time to Reach Cmax (Tmax) of ARO-MMP7(Pre-dose (Day 1) up to 168 hours post-dose (Day 8))
- MAD Cohorts: Tmax of ARO-MMP7(Pre-dose up to 6 hours post-dose on Days 1, 15, and 29)
- Change From Baseline to the End of Study (EOS) in Forced Expiratory Volume in One Second (FEV1)(Baseline, EOS (up to Day 85))
- Change From Baseline to the EOS in Forced Vital Capacity (FVC)(Baseline, EOS (up to Day 85))
- Change From Baseline to the EOS in Diffusing Capacity for Carbon Monoxide (DLCO)(Baseline, EOS (up to Day 85))
- SAD Cohorts: Maximum Observed Plasma Concentration (Cmax) of ARO-MMP7(Pre-dose (Day 1) up to 168 hours post-dose (Day 8))
- MAD Cohorts: Cmax of ARO-MMP7(Pre-dose up to 6 hours post-dose on Days 1, 15, and 29)
- IPF Cohorts: Cmax of ARO-MMP7(Pre-dose up to 6 hours post-dose on Days 1, 15, and 29)
- Urine PK of ARO-MMP7: Recovery of Unchanged Drug in Urine Over 0 to 24 Hours (Amount Excreted; Ae) in NHVs Enrolled in SAD Cohorts(Pre-dose up to 24 hours post-dose on Day 1)
- Urine PK of ARO-MMP7: Percentage of Administered Drug Recovered in Urine Over 0 to 24 Hours (Fraction Excreted; fe) in NHVs Enrolled in SAD Cohorts(Pre-dose up to 24 hours post-dose on Day 1)
- Urine PK of ARO-MMP7: Renal Clearance (CLr) in NHVs Enrolled in SAD Cohorts(Pre-dose up to 24 hours post-dose on Day 1)
研究者
研究点 (24)
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