A Randomized, Double-Blind, Placebo-Controlled, Phase 1b Clinical Study of the Safety, Tolerability, and Pharmacokinetics of MNKD-201 (Nintedanib Dry Powder Inhalation) in Patients With Idiopathic Pulmonary Fibrosis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 9
- 主要终点
- (Cohort 1) Events of Bronchospasm
研究概览
简要总结
MKC-NI-002 is a Phase 1b, randomized, double-blind, placebo-controlled study of nintedanib inhalation powder (MNKD-201) in patients with Idiopathic Pulmonary Fibrosis (IPF). The trial consists of Multiple Ascending Doses (MAD) with the primary objective to evaluate safety, tolerability and pharmacokinetics (PK) of MNKD-201 compared to placebo in patients with IPF.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 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
- •Is ≥40 to ≤85 years of age at the time of signing the informed consent form.
- •Diagnosis of IPF
- •Either treatment-naive or is currently on background pirfenidone or nerandomilast on a stable dose for at least 3 months prior to Screening.
- •Has FVC >45% of predicted of normal, as determined by the central spirometry reader, during Screening.
- •DLCO corrected for hemoglobin [Visit 1] ≥40% of predicted of normal, within 12 months of Screening. If no historical DLCO is available prior to Screening, this is to be done during Screening and read locally.
- •Has a body weight >40 kg (>88 lbs.) at Screening.
- •For female participants of childbearing potential, agreement to use acceptable birth control
- •For male participants who can father a child and are having intercourse with females of childbearing potential, agreement to use a protocol-recommended method of contraception
- •Is capable of performing spirometry, as required by the study procedures and ATS guidelines.
- •CT chest within 2 years of Screening, consistent with an IPF diagnosis, per investigator assessment.
排除标准
- •Known explanation for interstitial lung disease, including but not limited to radiation, sarcoidosis, hypersensitivity pneumonitis, and bronchiolitis obliterans organizing pneumonia.
- •Diagnosis of any connective tissue disease, including but not limited to scleroderma/systemic sclerosis, polymyositis/dermatomyositis, systemic lupus erythematosus, and rheumatoid arthritis, regardless of whether or not it is presumed to be related to their pulmonary fibrosis diagnosis.
- •Major extrapulmonary physiological restriction (e.g., chest wall abnormality, large pleural effusion), as determined by the investigator.
- •Significant Cardiovascular diseases
- •Recent systemic infection within 4 weeks before the Screening visit or symptomatic viral or bacterial infection at time of Screening.
- •Prior hospitalization for confirmed coronavirus disease 2019 (COVID-19), acute exacerbation of IPF or any lower respiratory tract infection within 3 months of Screening.
- •Has a history of asthma, with the exception of resolved childhood asthma.
- •Has known obstructive lung disease
- •Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin >1.5 times the upper limit of normal (ULN) during Screening.
- •Advanced liver and kidney function.
- •Current or recent (within 30 days of Screening) use of nintedanib.
- •Use of prednisone >10 mg/day within 1 month prior to Screening, or other significant immunosuppression
- •Active lung cancer (primary or metastatic) or any cancer requiring chemotherapy or radiation therapy within 3 years, except appropriately treated non-melanoma skin cancer, localized non-malignant prostate cancer, or in situ carcinoma of uterine cervix.
- •Has participated in another clinical study of a new chemical entity, new device, or a prescription medicine within the 1 month before Screening
- •Current alcohol, medication, or illicit drug abuse
- •Has lost more than 400 mL blood, e.g., as a blood donor, or donor of blood products, during the 3 months prior to Screening.
- •Has received a live vaccine within the 3 months prior to the first dose of study drug.
- •Smokes (any substance including electronic cigarettes and marijuana) within 3 months prior to Screening or is an ex-cigarette smoker who gave up <1 year ago.
- •Has oxygen requirement of > 6 liters/min at rest.
研究组 & 干预措施
Placebo
Participants will receive matching placebo across both cohorts of the study
干预措施: Placebo (Drug)
Cohort 1: MNKD-201 Target Dose or placebo
Participants will receive a target dose of MNKD-201 (Nintedanib DPI) or placebo, administered via oral inhalation three times daily for 7 days
干预措施: MNKD-201(Nintedanib DPI) (Drug)
Cohort 2: MNKD-201 High Dose or placebo
Participants will receive a high dose of MNKD-201 (Nintedanib DPI) or placebo, administered via oral inhalation twice daily for 7 days
干预措施: MNKD-201(Nintedanib DPI) (Drug)
结局指标
主要结局
(Cohort 1) Events of Bronchospasm
时间窗: Up to Day 7
The within-treatment number and proportion of participants with events of bronchospasm (e.g., treatment emergent adverse events \[TEAE\] immediately after inhalation of wheezing or chest tightness)
(Cohort 2) Events of Bronchospasm
时间窗: Up to Day 7
The within-treatment number and proportion of participants with events of bronchospasm (e.g., treatment emergent adverse events \[TEAE\] immediately after inhalation of wheezing or chest tightness)
(Cohort 1) Changes in FEV1 (mL) from pre-dose to post-dose
时间窗: Up to Day 7
The within-treatment number and proportion of participants with changes in FEV1 from pre-dose to any time post-dose
(Cohort 2) Changes in FEV1 (mL) from pre-dose to post-dose
时间窗: Up to Day 7
The within-treatment number and proportion of participants with changes in FEV1 from pre-dose to any time post-dose
(Cohort 1) Changes in FEV1 / FVC ratio from pre-dose to post-dose
时间窗: Up to Day 7
The within-treatment number and proportion of participants with changes in FEV1/FVC ratio from pre-dose to any time post-dose
(Cohort 2) Changes in FEV1 / FVC ratio from pre-dose to post-dose
时间窗: Up to Day 7
The within-treatment number and proportion of participants with changes in FEV1/FVC ratio from pre-dose to any time post-dose
(Cohort 1) Rate of Study Drug Discontinuations
时间窗: Up to Day 7
The within-treatment number and proportion of participants with study drug dose discontinuations
(Cohort 2) Rate of Study Drug Discontinuations
时间窗: Up to Day 7
The within-treatment number and proportion of participants with study drug dose discontinuations
(Cohort 1) Rate of Study Drug Dose Reductions
时间窗: Up to Day 7
The within-treatment number and proportion of participants with study drug dose reductions
(Cohort 2) Rate of Study Drug Dose Reductions
时间窗: Up to Day 7
The within-treatment number and proportion of participants with study drug dose reductions
(Cohort 1) Rate of Treatment Emergent Adverse Events (TEAEs)
时间窗: Up to Day 7
The within-treatment number and proportion of participants with TEAEs overall and by severity, relationship to study drug, and outcome
(Cohort 2) Rate of Treatment Emergent Adverse Events (TEAEs)
时间窗: Up to Day 7
The within-treatment number and proportion of participants with TEAEs overall and by severity, relationship to study drug, and outcome
(Cohort 1) Rate of Treatment Related Adverse Events (TRAEs)
时间窗: Up to Day 7
The within-treatment number and proportion of participants with TRAEs overall and by severity and outcome
(Cohort 2) Rate of Treatment Related Adverse Events (TRAEs)
时间窗: Up to Day 7
The within-treatment number and proportion of participants with TRAEs overall and by severity and outcome
(Cohort 1) Rate of Serious Adverse Events (SAEs)
时间窗: Up to Day 7
The within-treatment number and proportion of participants with SAEs overall and by severity, relationship to study drug, and outcome
(Cohort 2) Rate of Serious Adverse Events (SAEs)
时间窗: Up to Day 7
The within-treatment number and proportion of participants with SAEs overall and by severity, relationship to study drug, and outcome
次要结局
- Determine the maximum tolerated dose (MTD) of MKND-201 in patients with IPF(Up to Day 7)