Randomized, Double Blind, Placebo-controlled Study of the Safety, Tolerability and Pharmacokinetics After Single Ascending Doses or Multiple Ascending Doses of OSCN-, bLF or ALX-009 in Healthy Male and CF and Non-CF Bronchiectasis Patients
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Alaxia SAS
- 入组人数
- 92
- 试验地点
- 1
- 主要终点
- Safety and tolerability: number of subjects who experience serious adverse events, adverse events, potential clinically significant changes in ECG, 24-holter, vital signs, physical examinations, laboratory tests, spirometry, O2 saturation (Part III only)
研究概览
简要总结
This is a Phase 1, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability and pharmacokinetics of a single ascending doses (SAD) and multiple ascending doses (MAD) of Hypothiocyanite (OSCN-), bovine lactoferrin (bLF) and their combination (ALX-009) in healthy male volunteers and patients suffering from cystic fibrosis (CF) and non-CF bronchiectasis (NCFBE).
详细描述
Part I: SAD of OSCN- and bLF in healthy male volunteers (cohorts 1 to 3) - Part II: SAD and MAD of ALX-009 in healthy male volunteers (cohorts 4 and 5) - Part III: MAD of OSCN- and bLF in patients suffering from cystic fibrosis (cohort III-1) and in healthy volunteers (cohorts III-2 and III-3) - Part IV: MAD of ALX-009 in healthy volunteers (Part IVa - Cohorts IV-1a to IV-3a) and in patients (Part IVb - Cohorts IV-1b to IV-3b)
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
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male subject or
- •Patient suffering from cystic fibrosis defined as a positive sweat chloride test or CF-causing mutations, documented in the patient's medical record or patient suffering from non-CF and non COPD bronchiectasis with a diagnosis confirmed by a chest CT scan demonstrating bronchiectasis in 1 or more lobes documented in the patient's medical record
- •Aged between 18 and 50 years inclusive
- •Subject's Body Mass Index between 18 and 30 kg/m²
- •Subject with normal blood pressure, heart rate, ECG recording and laboratory parameters at the screening visit
- •Subject having given a written informed consent prior to selection
- •Subject covered by Health Insurance System and/ or in compliance with the recommendations of National Law in force relating to biomedical research
- •Specific Inclusion Criteria for patients:
- •FEV1 more than or equal to 60% of predicted normal value
- •Subject in a stable state (no exacerbation for 1 month or prescription of antibiotic by intravenous route)
- •Females of childbearing potential: commitment to consistently and correctly use an acceptable method of birth control for the duration of the trial and for 4 months after the last study drug administration / Female of non-childbearing potential: either surgically sterilized or at least 1 year postmenopausal
排除标准
- •Presence of cardiovascular, pulmonary, gastro-intestinal, hepatic, renal, metabolic, haematological, neurologic, psychiatric, systemic or infectious disease
- •Frequent headaches and/or migraines, recurrent nausea and/or vomiting
- •Symptomatic hypotension
- •Blood donation (including in the frame of a clinical trial) within 2 months before administration
- •General anaesthesia within 3 months before administration
- •Presence or history of drug hypersensitivity, or any allergic disease
- •Medical history of reactions to cow's milk proteins
- •Subject who can not be contacted in case of emergency
- •History or presence of drug or alcohol abuse
- •Positive Hepatitis B surface (HBs) antigen or anti Hepatitis C virus (HCV) antibody, or positive results for Human Immunodeficiency Virus (HIV) 1 or 2 tests
- •Subject who, in the judgement of the Investigator, is likely to be non-compliant or uncooperative during the study, or unable to cooperate because of a language problem, poor mental development.
- •Specific exclusion criteria for study Parts III and IV:
- •Known bronchial hyper-reactivity to drug inhalation
- •Known contra-indication to inhaled salbutamol
- •Subject with bronchial hyper-reactivity, defined by a positive response to bronchodilator with FEV1 increase ≥ 200 mL
- •Specific exclusion crtieria for patients:
- •Active allergic bronchopulmonary aspergillosis currently treated
- •Medical history of allergic bronchopulmonary aspergillosis in the past 2 years.
研究组 & 干预措施
Part I, SAD
Single administration of OSCN- or bLF or Placebo in healthy male volunteers
干预措施: OSCN- (Drug)
Part I, SAD
Single administration of OSCN- or bLF or Placebo in healthy male volunteers
干预措施: bLF (Drug)
Part I, SAD
Single administration of OSCN- or bLF or Placebo in healthy male volunteers
干预措施: Placebo (Drug)
Part II, SAD and MAD
Single and multiple administrations of ALX-009 or Placebo in healthy male volunteers
干预措施: ALX-009 (Drug)
Part II, SAD and MAD
Single and multiple administrations of ALX-009 or Placebo in healthy male volunteers
干预措施: Placebo (Drug)
Part III, MAD
Multiple administrations of OSCN- or bLF or Placebo in CF patients in healthy volunteers
干预措施: OSCN- (Drug)
Part III, MAD
Multiple administrations of OSCN- or bLF or Placebo in CF patients in healthy volunteers
干预措施: bLF (Drug)
Part III, MAD
Multiple administrations of OSCN- or bLF or Placebo in CF patients in healthy volunteers
干预措施: Placebo (Drug)
Part IV, MAD
Multiple administrations of ALX-009 or Placebo in healthy volunteers and in patients (CF and NCFBE)
干预措施: ALX-009 (Drug)
Part IV, MAD
Multiple administrations of ALX-009 or Placebo in healthy volunteers and in patients (CF and NCFBE)
干预措施: Placebo (Drug)
结局指标
主要结局
Safety and tolerability: number of subjects who experience serious adverse events, adverse events, potential clinically significant changes in ECG, 24-holter, vital signs, physical examinations, laboratory tests, spirometry, O2 saturation (Part III only)
时间窗: Day (D) 8 post dosing for part I and D14 post dosing for parts II, III and IV
次要结局
- First time to reach Cmax (Tmax) of bLF and SCN- in plasma, sputum and urine (for SCN- only)(D8 post dosing for part I and D14 post dosing for parts II, III and IV)
- Concentration half life of bLF and SCN- in plasma, sputum and urine (for SCN- only)(D8 post dosing for part I and D14 post dosing for parts II, III and IV)
- Area under the curve (AUC) of bLF and SCN- in plasma, sputum and urine (for SCN- only)(D8 post dosing for part I and D14 post dosing for parts II, III and IV)
- Concentration of IL-6 in blood and sputum(D8 post dosing for part I and D14 post dosing for parts II, III and IV)
- Concentration of IL-8 in blood and sputum(D8 post dosing for part I and D14 post dosing for parts II, III and IV)
- Concentration of TNF-α in blood and sputum(D8 post dosing for part I and D14 post dosing for parts II, III and IV)
- Maximal concentration (Cmax) of bLF and SCN- in plasma, sputum and urine (for SCN- only)(D8 post dosing for part I and D14 post dosing for parts II, III and IV)
- Concentration of IL-1β in blood and sputum(D8 post dosing for part I and D14 post dosing for parts II, III and IV)
- Concentration of anti-bLF antibodies in blood and sputum(D8 post dosing for part I and D14 post dosing for parts II, III and IV)
- Concentration of IL-10 in blood and sputum(D8 post dosing for part I and D14 post dosing for parts II, III and IV)
- For patients only, quantitative assessment of different species in sputum(D7 post dosing)
- Concentration of SC5b-9 in blood(D8 post dosing for part I and D14 post dosing for parts II, III and IV)
- Concentration of total IgE in blood(D8 post dosing for part I and D14 post dosing for parts II, III and IV)
- For patients only, volume of sputum over 24hours period(D8 post dosing)