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

January 20, 2022 updated by: Alaxia SAS

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

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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)

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
92

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Grenoble, France
        • Eurofins Optimed

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 Names:
  • Hypothiocyanite
Drug: bLF
Solution for inhalation administered through nebulization
Other Names:
  • 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: Placebo
Solution for inhalation administered through nebulization, Sodium Chloride 0.9%
Drug: ALX-009
Solution for inhalation administered through nebulization
Other Names:
  • Association of OSCN- and bLF
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 Names:
  • Hypothiocyanite
Drug: bLF
Solution for inhalation administered through nebulization
Other Names:
  • 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: Placebo
Solution for inhalation administered through nebulization, Sodium Chloride 0.9%
Drug: ALX-009
Solution for inhalation administered through nebulization
Other Names:
  • Association of OSCN- and bLF

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome 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)
Time Frame: Day (D) 8 post dosing for part I and D14 post dosing for parts II, III and IV
Day (D) 8 post dosing for part I and D14 post dosing for parts II, III and IV

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
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)
Time Frame: D8 post dosing for part I and D14 post dosing for parts II, III and IV
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)
Time Frame: D8 post dosing for part I and D14 post dosing for parts II, III and IV
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)
Time Frame: D8 post dosing for part I and D14 post dosing for parts II, III and IV
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
Time Frame: D8 post dosing for part I and D14 post dosing for parts II, III and IV
D8 post dosing for part I and D14 post dosing for parts II, III and IV
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
D8 post dosing for part I and D14 post dosing for parts II, III and IV
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
D8 post dosing for part I and D14 post dosing for parts II, III and IV
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
D8 post dosing for part I and D14 post dosing for parts II, III and IV
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
D8 post dosing for part I and D14 post dosing for parts II, III and IV
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
D8 post dosing for part I and D14 post dosing for parts II, III and IV
Concentration of SC5b-9 in blood
Time Frame: D8 post dosing for part I and D14 post dosing for parts II, III and IV
D8 post dosing for part I and D14 post dosing for parts II, III and IV
Concentration of total IgE in blood
Time Frame: D8 post dosing for part I and D14 post dosing for parts II, III and IV
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
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
D7 post dosing
For patients only, volume of sputum over 24hours period
Time Frame: D8 post dosing
D8 post dosing

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Time Frame
For patients only, characterization of sputum microbiota using genomic technologies
Time Frame: D14 post dosing
D14 post dosing

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Alaxia SAS

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Isabelle Durieu, Prof., MD, Hospices Civils de Lyon

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 4, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 5, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 6, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 3, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 20, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ALX-009-CL-038
  • 2014-002401-38 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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