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

Primary Purpose

Cystic Fibrosis, Bronchiectasis

Status

Terminated

Phase

Phase 1

Locations

France

Study Type

Interventional

Intervention

ALX-009

OSCN-

bLF

Placebo

About this trial

This is an interventional treatment trial for Cystic Fibrosis

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

Eurofins Optimed

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Part I, SAD

Part II, SAD and MAD

Part III, MAD

Part IV, MAD

Arm Description

Single administration of OSCN- or bLF or Placebo in healthy male volunteers

Single and multiple administrations of ALX-009 or Placebo in healthy male volunteers

Multiple administrations of OSCN- or bLF or Placebo in CF patients in healthy volunteers

Multiple administrations of ALX-009 or Placebo in healthy volunteers and in patients (CF and NCFBE)

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

Maximal concentration (Cmax) of bLF and SCN- in plasma, sputum and urine (for SCN- only)

Area under the curve (AUC) of bLF and SCN- in plasma, sputum and urine (for SCN- only)

First time to reach Cmax (Tmax) of bLF and SCN- in plasma, sputum and urine (for SCN- only)

Concentration half life of bLF and SCN- in plasma, sputum and urine (for SCN- only)

Concentration of anti-bLF antibodies in blood and sputum

Concentration of IL-1β in blood and sputum

Concentration of IL-6 in blood and sputum

Concentration of IL-8 in blood and sputum

Concentration of IL-10 in blood and sputum

Concentration of TNF-α in blood and sputum

Concentration of SC5b-9 in blood

Concentration of total IgE in blood

For patients only, quantitative assessment of different species in sputum

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

Full Information

NCT ID

NCT02598999

First Posted

November 4, 2015

Last Updated

January 20, 2022

Sponsor

Alaxia SAS

1. Study Identification

Unique Protocol Identification Number

NCT02598999

Brief Title

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

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 Type

Interventional

2. Study Status

Record Verification Date

January 2022

Overall Recruitment Status

Terminated

Why Stopped

Financial issues

Study Start Date

November 2015 (Actual)

Primary Completion Date

December 2021 (Actual)

Study Completion Date

December 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Alaxia SAS

4. Oversight

Data Monitoring Committee

5. Study Description

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cystic Fibrosis, Bronchiectasis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

92 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part I, SAD

Arm Type

Experimental

Arm Description

Single administration of OSCN- or bLF or Placebo in healthy male volunteers

Arm Title

Part II, SAD and MAD

Arm Type

Experimental

Arm Description

Single and multiple administrations of ALX-009 or Placebo in healthy male volunteers

Arm Title

Part III, MAD

Arm Type

Experimental

Arm Description

Multiple administrations of OSCN- or bLF or Placebo in CF patients in healthy volunteers

Arm Title

Part IV, MAD

Arm Type

Experimental

Arm Description

Multiple administrations of ALX-009 or Placebo in healthy volunteers and in patients (CF and NCFBE)

Intervention Type

Drug

Intervention Name(s)

ALX-009

Other Intervention Name(s)

Association of OSCN- and bLF

Intervention Description

Solution for inhalation administered through nebulization

Intervention Type

Drug

Intervention Name(s)

OSCN-

Other Intervention Name(s)

Hypothiocyanite

Intervention Description

Solution for inhalation administered through nebulization

Intervention Type

Drug

Intervention Name(s)

bLF

Other Intervention Name(s)

bovine Lactoferrin

Intervention Description

Solution for inhalation administered through nebulization

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Solution for inhalation administered through nebulization, Sodium Chloride 0.9%

Primary Outcome Measure Information:

Title

Time Frame

Day (D) 8 post dosing for part I and D14 post dosing for parts II, III and IV

Secondary Outcome Measure Information:

Title

Maximal concentration (Cmax) of bLF and SCN- in plasma, sputum and urine (for SCN- only)

Time Frame