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

NCT02598999 | Terminated Phase 1

• 2 other identifiers: ALX-009-CL-0382014-002401-38
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 1

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).

Conditions

Cystic Fibrosis; Bronchiectasis

Outcome Measures

Primary Outcomes (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)

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

Secondary Outcomes (14)

• 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 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

Other Outcomes (1)

• For patients only, characterization of sputum microbiota using genomic technologies

  D14 post dosing

Study Arms (4)

Part I, SAD

EXPERIMENTAL

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

Drug: OSCN-; Drug: bLF; Drug: Placebo

Part II, SAD and MAD

EXPERIMENTAL

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

Drug: ALX-009; Drug: Placebo

Part III, MAD

EXPERIMENTAL

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

Drug: OSCN-; Drug: bLF; Drug: Placebo

Part IV, MAD

EXPERIMENTAL

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

Drug: ALX-009; Drug: Placebo

Interventions

ALX-009 DRUG

Solution for inhalation administered through nebulization

Also known as: Association of OSCN- and bLF

Part II, SAD and MAD; Part IV, MAD

OSCN- DRUG

Solution for inhalation administered through nebulization

Also known as: Hypothiocyanite

Part I, SAD; Part III, MAD

bLF DRUG

Solution for inhalation administered through nebulization

Also known as: bovine Lactoferrin

Part I, SAD; Part III, MAD

Placebo DRUG

Solution for inhalation administered through nebulization, Sodium Chloride 0.9%

Part I, SAD; Part II, SAD and MAD; Part III, MAD; Part IV, MAD

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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
• Active allergic bronchopulmonary aspergillosis currently treated

Sponsors & Collaborators

• Alaxia SAS: lead

Study Sites (1)

Eurofins Optimed

Grenoble, France

Location

MeSH Terms

Conditions

Cystic Fibrosis; Bronchiectasis

Interventions

hypothiocyanite ion

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Bronchial Diseases

Study Officials

• Isabelle Durieu, Prof., MD

  Hospices Civils de Lyon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2015
• First Posted: November 6, 2015
• Study Start: November 1, 2015
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2021
• Last Updated: February 3, 2022

Record last verified: 2022-01

Locations

FR (1)