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Dose Escalation Study of ALX-009 in Healthy Men and Cystic Fibrosis (CF) and Non-CF Bronchiectasis Patients

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ClinicalTrials.gov Identifier: NCT02598999
Recruitment Status : Recruiting
First Posted : November 6, 2015
Last Update Posted : May 1, 2019
Sponsor:
Information provided by (Responsible Party):
Alaxia SAS

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).

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Bronchiectasis Drug: ALX-009 Drug: OSCN- Drug: bLF Drug: Placebo Phase 1

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)

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 103 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : November 2015
Estimated Primary Completion Date : February 2020
Estimated Study Completion Date : February 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cystic Fibrosis

Arm Intervention/treatment
Experimental: Part I, SAD
Single administration of OSCN- or bLF or Placebo in healthy male volunteers
Drug: OSCN-
Solution for inhalation administered through nebulization
Other Name: Hypothiocyanite

Drug: bLF
Solution for inhalation administered through nebulization
Other Name: bovine Lactoferrin

Drug: Placebo
Solution for inhalation administered through nebulization, Sodium Chloride 0.9%

Experimental: Part II, SAD and MAD
Single and multiple administrations of ALX-009 or Placebo in healthy male volunteers
Drug: ALX-009
Solution for inhalation administered through nebulization
Other Name: Association of OSCN- and bLF

Drug: Placebo
Solution for inhalation administered through nebulization, Sodium Chloride 0.9%

Experimental: Part III, MAD
Multiple administrations of OSCN- or bLF or Placebo in CF patients in healthy volunteers
Drug: OSCN-
Solution for inhalation administered through nebulization
Other Name: Hypothiocyanite

Drug: bLF
Solution for inhalation administered through nebulization
Other Name: bovine Lactoferrin

Drug: Placebo
Solution for inhalation administered through nebulization, Sodium Chloride 0.9%

Experimental: Part IV, MAD
Multiple administrations of ALX-009 or Placebo in healthy volunteers and in patients (CF and NCFBE)
Drug: ALX-009
Solution for inhalation administered through nebulization
Other Name: Association of OSCN- and bLF

Drug: Placebo
Solution for inhalation administered through nebulization, Sodium Chloride 0.9%




Primary Outcome Measures :
  1. 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) [ Time Frame: Day (D) 8 post dosing for part I and D14 post dosing for parts II, III and IV ]

Secondary Outcome Measures :
  1. Maximal concentration (Cmax) of bLF and SCN- in plasma, sputum and urine (for SCN- only) [ Time Frame: D8 post dosing for part I and D14 post dosing for parts II, III and IV ]
  2. Area under the curve (AUC) of bLF and SCN- in plasma, sputum and urine (for SCN- only) [ Time Frame: D8 post dosing for part I and D14 post dosing for parts II, III and IV ]
  3. First time to reach Cmax (Tmax) of bLF and SCN- in plasma, sputum and urine (for SCN- only) [ Time Frame: D8 post dosing for part I and D14 post dosing for parts II, III and IV ]
  4. Concentration half life of bLF and SCN- in plasma, sputum and urine (for SCN- only) [ Time Frame: D8 post dosing for part I and D14 post dosing for parts II, III and IV ]
  5. Concentration of anti-bLF antibodies in blood and sputum [ Time Frame: D8 post dosing for part I and D14 post dosing for parts II, III and IV ]
  6. Concentration of IL-1β in blood and sputum [ Time Frame: D8 post dosing for part I and D14 post dosing for parts II, III and IV ]
  7. Concentration of IL-6 in blood and sputum [ Time Frame: D8 post dosing for part I and D14 post dosing for parts II, III and IV ]
  8. Concentration of IL-8 in blood and sputum [ Time Frame: D8 post dosing for part I and D14 post dosing for parts II, III and IV ]
  9. Concentration of IL-10 in blood and sputum [ Time Frame: D8 post dosing for part I and D14 post dosing for parts II, III and IV ]
  10. Concentration of TNF-α in blood and sputum [ Time Frame: D8 post dosing for part I and D14 post dosing for parts II, III and IV ]
  11. Concentration of SC5b-9 in blood [ Time Frame: D8 post dosing for part I and D14 post dosing for parts II, III and IV ]
  12. Concentration of total IgE in blood [ Time Frame: D8 post dosing for part I and D14 post dosing for parts II, III and IV ]
  13. For patients only, quantitative assessment of different species in sputum [ Time Frame: 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

  14. For patients only, volume of sputum over 24hours period [ Time Frame: D8 post dosing ]

Other Outcome Measures:
  1. For patients only, characterization of sputum microbiota using genomic technologies [ Time Frame: D14 post dosing ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02598999


Contacts
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Contact: Annie-Claude BENICHOU, MD +33 478 42 95 26

Locations
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France
Eurofins Optimed Recruiting
Grenoble, France
Contact: Yves Donazzolo         
Sponsors and Collaborators
Alaxia SAS
Investigators
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Principal Investigator: Isabelle Durieu, Prof., MD Hospices Civils de Lyon

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Responsible Party: Alaxia SAS
ClinicalTrials.gov Identifier: NCT02598999     History of Changes
Other Study ID Numbers: ALX-009-CL-038
2014-002401-38 ( EudraCT Number )
First Posted: November 6, 2015    Key Record Dates
Last Update Posted: May 1, 2019
Last Verified: April 2019

Additional relevant MeSH terms:
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Fibrosis
Cystic Fibrosis
Bronchiectasis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Bronchial Diseases
Hypothiocyanite ion
Anti-Infective Agents