Bronchiectasis, Cystic Fibrosis
Conditions
Brief summary
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).
Detailed description
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)
Interventions
DRUGbLF
Solution for inhalation administered through nebulization
DRUGALX-009
Solution for inhalation administered through nebulization
DRUGOSCN-
Solution for inhalation administered through nebulization
DRUGPlacebo
Solution for inhalation administered through nebulization, Sodium Chloride 0.9%
Sponsors
Alaxia SAS
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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) | Day (D) 8 post dosing for part I and D14 post dosing for parts II, III and IV |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 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 | — |
| 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 | — |
| 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 | — |
| 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 | — |
| 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 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-10 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 | — |
| 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, quantitative assessment of different species in sputum | D7 post dosing | Staphylococcus aureus, Staphylococcus aureus MRSA, Pseudomonas aeruginosa, Pseudomonas aeruginosa MDR, Haemophilus influenzae, Stenotrophomonas maltophilia, Achromobacter xylosoxidans, Burkholderia cepacia complex, Aspergillus fumigatus and Aspergillus terreus |
| For patients only, volume of sputum over 24hours period | D8 post dosing | — |
| Concentration of IL-8 in blood and sputum | D8 post dosing for part I and D14 post dosing for parts II, III and IV | — |
Other
| Measure | Time frame |
|---|---|
| For patients only, characterization of sputum microbiota using genomic technologies | D14 post dosing |
Countries
France
Outcome results
None listed