A Phase Ib, Randomised, Double-blind, Placebo-controlled Study to Investigate the Safety, Tolerability, and Pharmacokinetics of an Intravenous Monoclonal Antibody (mAb) After Single Ascending Doses in Subjects Affected by Idiopathic Pulmonary Fibrosis.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 52
- 试验地点
- 9
- 主要终点
- 1_Subjects With Adverse Event (AE); Non-Serious AEs and Serious AEs
研究概览
简要总结
Assess the safety of CHF10067 (study drug) and any side effects that might be associated with it. The study also evaluated how much of the study drug gets into the bloodstream and how long the body takes to remove it. The body's immune response to the study drug was evaluated.
Chiesi conducted this study in patients affected by idiopathic pulmonary fibrosis (IPF, a progressive and chronic lung disease). Chiesi performed this study to establish the drug doses that would be suitable for future studies (a dose finding study).
详细描述
The principal aim of this study was to obtain safety and tolerability data when CHF10067 was administered intravenously as single ascending doses to subjects with IPF (a progressive and chronic lung disease). This information, together with the pharmacokinetic (PK) and immunogenicity data is part of a dose finding efforts, for future clinical studies. The effect of CHF10067 on transglutaminase 2 (TG2) levels was also investigated as an exploratory endpoint.
A sequential group, single ascending dose design has been chosen for safety reasons because CHF10067 is in the early stages of clinical development and no data in the IPF population has been collected so far. In addition, sentinel dosing was used so that in each cohort 2 subjects (1 CHF10067 and 1 placebo) was administered at least 24 hours, before the remaining 6 subjects.
The study was double-blind and placebo-controlled to avoid bias in the collection and evaluation of data during its conduct. Placebo was chosen as the comparison treatment to assess whether any observed effects are treatment-related or reflect the study conditions.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The Investigational Medicinal Product (IMP) was blinded for the participant, investigators, and the sponsor. At the study site an unblinded pharmacist (or designee) prepared the IMP and an unblinded clinical research associate checked the documents of the IMP preparation.
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject's written informed consent obtained prior to any study-related procedure.
- •Males or females, of any race, aged ≥ 40 years of age.
- •Body weight ≥ 45 kg.
- •Diagnosis of IPF as defined by current American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association guidelines. Diagnosis of IPF must be within the past 5 years prior to enrolment, and in the opinion of the Investigator, has been stable for at least 3 months.
- •Subjects not receiving any IPF treatment (including subjects with previous use of antifibrotic treatment that has been stopped for at least 2 weeks prior to screening) or receiving well-tolerated standard of care approved treatments at a stable dose for at least 8 weeks prior to screening (nintedanib or pirfenidone) and it is anticipated the dose will remain unchanged throughout the study.
- •Forced vital capacity (FVC) ≥ 50% of predicted and ratio of forced expiratory volume in the first second (FEV1)/FVC ≥ 0.7 at screening.
- •Diffusing capacity of the lung for carbon monoxide (DLCO; corrected for haemoglobin) ≥ 35% at screening.
- •Able to understand the study procedures and the risks involved.
- •Male and Female subjects following contraceptive requirements detailed in the study protocol.
排除标准
- •History of lower respiratory tract infection within 4 weeks prior to screening and up to Day 1 of the study.
- •History of acute exacerbation of IPF within 3 months prior to screening and up to Day 1 of the study
- •Active diagnosis of lung cancer or a history of lung cancer.
- •Active cancer or a history of cancer (other than lung cancer) with less than 5 years disease free survival time (whether or not there is evidence of local recurrence or metastases).
- •Infiltrative lung disease other than IPF
- •Subjects exhibiting unhealed wounds or foot ulcers or have known history of wound healing complications.
- •Chronic heart failure categorized as New York Heart Association Class II, III, or IV; clinical diagnosis of cor pulmonale requiring specific treatment; or severe pulmonary hypertension
- •Currently receiving, or have received, a systemic corticosteroid, immunosuppressant, cytotoxic therapy, vasodilator therapy for pulmonary hypertension, or unapproved or investigational treatment for IPF within 4 weeks prior to screening or prior to randomization.
- •Coronavirus disease-2019 (COVID-19) vaccine at least 7 days before dosing. Any systemic symptoms (e.g. myalgia, fever, chills, fatigue, etc.) after COVID-19 vaccine should subside at least 2 days before the Day 1 visit.
- •Documented COVID-19 diagnosis within the last 4 weeks or which has not resolved within 7 days prior to screening or before treatment.
- •Known intolerance and/or hypersensitivity to any of the excipients contained in the formulation or any other substance used in the study.
- •History of allergic or anaphylactic reaction to human, humanised, chimeric, immunoglobulins (Igs), or murine monoclonal antibodies.
- •Clinically relevant abnormal laboratory values (clinical chemistry and haematology) at screening suggesting an unknown disease and requiring further clinical investigation or which may impact the safety of the subject or the evaluation of the study results according to Investigator judgement. .
- •Pregnant or lactating women.
研究组 & 干预措施
Test Treatment
A single intravenous (IV) dose of CHF10067
干预措施: CHF10067 starting dose -- 1000mg (Cohort A) (Biological)
Test Treatment
A single intravenous (IV) dose of CHF10067
干预措施: CHF10067 intermediate dose -- 2000mg (Cohort B) (Biological)
Test Treatment
A single intravenous (IV) dose of CHF10067
干预措施: CHF10067 high dose -- 3000mg (Cohort C) (Biological)
Reference treatment
A single dose of placebo (commercial source of 0.9% sodium chloride aqueous solution)
干预措施: Placebo (Drug)
结局指标
主要结局
1_Subjects With Adverse Event (AE); Non-Serious AEs and Serious AEs
时间窗: From pre-dose (baseline) up to day 84.
Evaluate reported adverse events (AEs) and serious adverse events (SAEs). The number of subjects affected by AEs or SAEs is presented below. Please note: comprehensive summaries of AEs and SAEs are presented in section 'Adverse Events'; these include the preferred term of the AE or SAE, the number of subjects affected, and the number of events for a each preferred term.
次要结局
- 2_Systemic Exposure [Area Under the Concentration-time Curve From Zero to Time (AUC0-t)](Pre-dose (within 75 min from start of infusion, baseline), at the end of infusion, 2, 4, 8, and 20 h after the end of infusion and 5, 7, 14, 28, 56, and 84 days post-dose.)
- 3_Area Under the Concentration-time Curve (AUC) From Zero to Infinity (AUC0-∞)(Pre-dose (within 75 min from start of infusion, baseline), at the end of infusion, 2, 4, 8, and 20 h after the end of infusion and 5, 7, 14, 28, 56, and 84 days post-dose.)
- 4_Pharmacokinetics -- Maximum Plasma Concentration (Cmax)(Pre-dose (within 75 min from start of infusion, baseline), at the end of infusion, 2, 4, 8, and 20 h after the end of infusion and 5, 7, 14, 28, 56, and 84 days post-dose.)
- 5_Pharmacokinetics -- Time to Maximum Observed Concentration (Tmax)(Pre-dose (within 75 min from start of infusion, baseline), at the end of infusion, 2, 4, 8, and 20 h after the end of infusion and 5, 7, 14, 28, 56, and 84 days post-dose.)
- 6_Pharmacokinetics -- Serum Concentration at the End of Infusion (Cinf)(Pre-dose (within 75 min from start of infusion, baseline), at the end of infusion (up to 6 hours from the start of infusion).)
- 7_Pharmacokinetics -- Time at the End of Infusion (Tinf)(Pre-dose (within 75 min from start of infusion, baseline), at the end of infusion (up to 6 hours from the start of infusion).)
- 8_Pharmacokinetics -- Clearance (CL)(Pre-dose (within 75 min from start of infusion, baseline), at the end of infusion, 2, 4, 8, and 20 h after the end of infusion and 5, 7, 14, 28, 56, and 84 days post-dose.)
- 9_Pharmacokinetics -- Volume of Distribution (Vz)(Pre-dose (within 75 min from start of infusion, baseline), at the end of infusion, 2, 4, 8, and 20 h after the end of infusion and 5, 7, 14, 28, 56, and 84 days post-dose.)
- 10_Pharmacokinetics -- Terminal Half-life (t1/2)(From pre-dose (baseline) up to day 84.)
- 11_Spirometry -- Forced Expiratory Volume in the First Second (FEV1) -- Percent Predicted -- Change From Baseline(Pre-dose (baseline), and on 7, 28, 56, and 84 day post-dose.)
- 12_Spirometry -- Forced Vital Capacity (FVC) -- Percent Predicted -- Change From Baseline(Text adjusted Pre-dose (baseline), and on 7, 28, 56, and 84 day post-dose.)
- 13_Vital Signs -- Abnormal Changes in Systolic and Diastolic Blood Pressure(From pre-dose (baseline) up to day 84.)
- 14_Immunogenicity Profile -- Anti-drug Antibody (ADA) and Neutralising Antibody (nAb).(Pre-dose (baseline), at day 14, 28, 56, 84, and in case of early termination.)