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

NCT ID: NCT02598999

Last Updated: 2022-02-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 92 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-30
• Study Completion Date: 2021-12-31

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)

Conditions

Cystic Fibrosis; Bronchiectasis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Part I, SAD

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

Group Type: EXPERIMENTAL

OSCN-

Intervention Type: DRUG

Solution for inhalation administered through nebulization

bLF

Intervention Type: DRUG

Solution for inhalation administered through nebulization

Placebo

Intervention Type: DRUG

Solution for inhalation administered through nebulization, Sodium Chloride 0.9%

Part II, SAD and MAD

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

Group Type: EXPERIMENTAL

ALX-009

Intervention Type: DRUG

Solution for inhalation administered through nebulization

Placebo

Intervention Type: DRUG

Solution for inhalation administered through nebulization, Sodium Chloride 0.9%

Part III, MAD

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

Group Type: EXPERIMENTAL

OSCN-

Intervention Type: DRUG

Solution for inhalation administered through nebulization

bLF

Intervention Type: DRUG

Solution for inhalation administered through nebulization

Placebo

Intervention Type: DRUG

Solution for inhalation administered through nebulization, Sodium Chloride 0.9%

Part IV, MAD

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

Group Type: EXPERIMENTAL

ALX-009

Intervention Type: DRUG

Solution for inhalation administered through nebulization

Placebo

Intervention Type: DRUG

Solution for inhalation administered through nebulization, Sodium Chloride 0.9%

Interventions

ALX-009

Solution for inhalation administered through nebulization

Intervention Type: DRUG

OSCN-

Solution for inhalation administered through nebulization

Intervention Type: DRUG

bLF

Solution for inhalation administered through nebulization

Intervention Type: DRUG

Placebo

Solution for inhalation administered through nebulization, Sodium Chloride 0.9%

Intervention Type: DRUG

Other Intervention Names

Association of OSCN- and bLF; Hypothiocyanite; bovine Lactoferrin

Eligibility 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

• 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.

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Alaxia SAS

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Isabelle Durieu, Prof., MD

Role: PRINCIPAL_INVESTIGATOR

Hospices Civils de Lyon

Locations

Eurofins Optimed

Grenoble, , France

Countries

France

Other Identifiers

2014-002401-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ALX-009-CL-038

Identifier Type: -

Identifier Source: org_study_id