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

• Register: ClinicalTrials.gov
• Last refreshed on: 26 April 2021
• Main ID: NCT02598999
• Date of registration: 04/11/2015
• Prospective Registration: No
• Primary sponsor: Alaxia SAS
• Public title: Dose Escalation Study of ALX-009 in Healthy Men and Cystic Fibrosis (CF) and Non-CF Bronchiectasis Patients
• Scientific 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
• Date of first enrolment: November 2015
• Target sample size: 103
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/show/NCT02598999
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 1

Countries of recruitment

France

Contacts

• Name: Isabelle Durieu, Prof., MD
• Affiliation: Hospices Civils de Lyon

• Name: Annie-Claude BENICHOU, MD

• Name: Yves Donazzolo

Key inclusion & exclusion 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

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.



Age minimum: 18 Years
Age maximum: 50 Years
Gender: All

Health Condition(s) or Problem(s) studied

Bronchiectasis

Cystic Fibrosis

Intervention(s)

Drug: ALX-009

Drug: bLF

Drug: Placebo

Drug: OSCN-

Primary Outcome(s)

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]

Secondary Outcome(s)

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]

Concentration of IL-1ß in blood and sputum [Time Frame: D8 post dosing for part I and D14 post dosing for parts II, III and IV]

Concentration of TNF-a in blood and sputum [Time Frame: 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]

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]

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]

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]

Concentration of total IgE in blood [Time Frame: 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]

For patients only, volume of sputum over 24hours period [Time Frame: D8 post dosing]

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]

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]

For patients only, quantitative assessment of different species in sputum [Time Frame: D7 post dosing]

Concentration of SC5b-9 in blood [Time Frame: D8 post dosing for part I and D14 post dosing for parts II, III and IV]

Secondary ID(s)

2014-002401-38

ALX-009-CL-038

Source(s) of Monetary Support

Please refer to primary and secondary sponsors