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

Alaxia

Status and phase: Terminated; Phase 1

Conditions: Bronchiectasis; Cystic Fibrosis

Treatments: Drug: Placebo; Drug: OSCN-; Drug: ALX-009; Drug: bLF

Study type: Interventional

Funder types: Industry

Identifiers

NCT02598999

ALX-009-CL-038

2014-002401-38 (EudraCT Number)

Details and patient eligibility

About

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).

Full 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)

Enrollment: 92 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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92 participants in 4 patient groups

Part I, SAD

Experimental group

Description:

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

Treatment:

Drug: bLF

Drug: OSCN-

Drug: Placebo

Part II, SAD and MAD

Experimental group

Description:

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

Treatment:

Drug: ALX-009

Drug: Placebo

Part III, MAD

Experimental group

Description:

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

Treatment:

Drug: bLF

Drug: OSCN-

Drug: Placebo

Part IV, MAD

Experimental group

Description:

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

Treatment:

Drug: ALX-009

Drug: Placebo