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ALX-0171 Phase I Pharmacokinetic Study in Healthy Male Volunteers

12 juillet 2018 mis à jour par: Ablynx

Phase I, Single-centre, Open-label Study to Evaluate the Pharmacokinetics of ALX-0171, Administered by Oral Inhalation or Intravenously, in Healthy Male Volunteers

The overall aims of the study are:

  • To provide additional information on the pharmacokinetics of ALX-0171 by measuring (i) local (bronchoalveolar lavage fluid (BALF)) and systemic (plasma) concentrations of ALX-0171 after oral inhalation, and (ii) systemic (plasma) and urine concentrations after intravenous administration.
  • To further determine the safety and local and systemic tolerability of ALX-0171.
  • To further evaluate local (induced sputum) and/or systemic (serum) immunogenicity of ALX-0171, by analysing the potential occurrence of anti-drug antibodies (ADA).

Aperçu de l'étude

Type d'étude

Interventionnel

Inscription (Réel)

44

Phase

  • La phase 1

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 55 ans (Adulte)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Homme

La description

Inclusion Criteria:

  1. Non-smoking healthy male volunteers, (18-55 years, extremes included).
  2. Good health condition, as determined by medical history, physical examination and clinical laboratory testing
  3. Body mass index (BMI) within normal range: 18.0 ≤ BMI < 30.0 (kg/m2)
  4. Haematology and chemistry parameters within normal range, or showing no clinically relevant deviations (as judged by the Investigator)
  5. Heart rate and/or blood pressure within normal range (as judged by the Investigator)
  6. Electrocardiogram (ECG) within normal range, or showing no clinically relevant deviations (as judged by the Investigator)
  7. Negative urine test for selected drugs of abuse at screening
  8. Negative alcohol breath test upon check-in at study unit
  9. Negative hepatitis panel (including hepatitis B surface antigen (HBsAg) and anti-hepatitis C virus antibodies (anti-HCV)), and negative human immunodeficiency virus (HIV) antibody screens
  10. Willingness to consent to using an effective contraceptive method (by using 2 methods of contraception in combination with a female partner: at least 1 of the contraception methods must be a barrier contraception method, e.g., condom) during the study and for at least 3 months after last study drug administration
  11. Ability to comprehend and willingness to sign an Informed Consent Form (ICF)

    For oral inhalation only:

  12. Lung function test which shows a Forced Expiratory Volume in 1 second (FEV1) ≥ 90% of predicted value
  13. Ability to retro-breathe with nebulizer
  14. Height between 170 and 190 cm (extremes included)
  15. Ability to produce a sufficient amount of induced sputum (at least 400 μL containing visual sputum plugs) to assess immunogenicity

Exclusion Criteria:

  1. Current smokers, or ex-smokers abstinent from tobacco for less than one year, or a history of smoking more than 10 packs a year
  2. Symptomatic viral infection, or suspicion thereof (including rhinitis) in the last 14 days prior to dosing
  3. Signs of active pulmonary infection or other pulmonary inflammatory conditions, even in the absence of febrile episodes, in the last 14 days prior to dosing
  4. History or presence of disease in the kidneys and/or heart, lungs, liver, gastrointestinal tract, endocrine organs or other conditions such as metabolic disease known to interfere with the absorption, distribution, metabolism or excretion of drugs
  5. Malignancy, or prior malignancy, with a disease-free interval of < 5 years after diagnosis and intervention, except basal cell carcinoma (treated curatively)
  6. Autoimmune disorders such as (but not limited to) lupus erythematosus, multiple sclerosis, rheumatoid arthritis, or sarcoidosis.
  7. History of hypersensitivity or allergies to any drug compound, including constituents of ALX-0171
  8. History of previous administration of ALX-0171, or any other inhaled biologic or drug targeting the Respiratory Syncytial Virus (RSV) F protein. In any other case of use of biologics: at least 6 months before administration of first study medication, or the time of duration of the pharmacodynamic effect, or 10 times the half-life of the respective drug, whatever is longer
  9. Receipt of any investigational drug within 60 days prior to dosing
  10. Intake of prescribed or over-the-counter medication within 14 days prior to dosing (≤ 3 g/day paracetamol is allowed)
  11. History or presence of alcohol or drug abuse
  12. Blood donation (> 500 mL) or a comparable blood loss within three months prior to dosing
  13. Planned donation of germ cells, blood, organs, bone marrow during the course of the study or within 6 months thereafter
  14. Any other condition or prior therapy which, in the opinion of the Investigator, would make the subject unsuitable for this study
  15. Vulnerable subjects (e.g., persons kept in detention)

    For oral inhalation only:

  16. History or presence of atopy or any condition associated with airway hyperresponsiveness (e.g., allergic or non-allergic asthma, chronic obstructive pulmonary disease (COPD))
  17. FEV1 drop of > 10% after inhalation of 4 mL of ALX-0171 placebo (measured at 5 min after the end of inhalation)
  18. Contra-indication for sputum induction, such as (but not limited to) recent eye surgery, recent fractured ribs and recent (or history of) pneumothorax

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Non randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: ALX-0171 Oral Inhalation - Single Dose (SD)
single dose of 200 mg ALX-0171 via oral inhalation
repeated doses of 200 mg ALX-0171 via oral inhalation once daily for 5 consecutive days
Single dose of 0.3 mg/kg body weight ALX-0171 via intravenous administration
Expérimental: ALX-0171 Oral Inhalation - Multiple Dose (MD)
single dose of 200 mg ALX-0171 via oral inhalation
repeated doses of 200 mg ALX-0171 via oral inhalation once daily for 5 consecutive days
Single dose of 0.3 mg/kg body weight ALX-0171 via intravenous administration
Expérimental: ALX-0171 Intravenous (IV)
single dose of 200 mg ALX-0171 via oral inhalation
repeated doses of 200 mg ALX-0171 via oral inhalation once daily for 5 consecutive days
Single dose of 0.3 mg/kg body weight ALX-0171 via intravenous administration

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Délai
Pharmacokinetics: concentration of ALX-0171 after oral inhalation in BALF samples and in plasma samples
Délai: Day 1 to Day 9
Day 1 to Day 9
Pharmacokinetics: ALX-0171 concentration in plasma and urine after intravenous administration
Délai: Day 1 to Day 4
Day 1 to Day 4

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Safety and tolerability: safety markers
Délai: from signing of Informed Consent Form (ICF) until last follow-up visit (i.e 35 to 42 days after first study drug administration)
  • Lung function test pre- and post-inhalation with 4 mL of ALX-0171 placebo (on Day -1, applicable for oral inhalation only).
  • Lung function tests
  • Physical examination (including physical examination of the lung for oral inhalation)
  • Vital signs
  • 12-lead ECG.
  • Clinical laboratory
  • Limited safety lab (haematology + limited chemistry).
  • Adverse events (AEs) and concomitant medication
from signing of Informed Consent Form (ICF) until last follow-up visit (i.e 35 to 42 days after first study drug administration)
Immunogenicity: concentration of Anti-Drug Antibodies (ADA)in induced sputum (after oral inhalation only) and serum
Délai: during screening until last follow-up visit (i.e. 35 to 42 days after first study drug administration)
during screening until last follow-up visit (i.e. 35 to 42 days after first study drug administration)

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

1 mai 2013

Achèvement primaire (Réel)

1 octobre 2013

Achèvement de l'étude (Réel)

1 octobre 2013

Dates d'inscription aux études

Première soumission

10 juin 2013

Première soumission répondant aux critères de contrôle qualité

11 juin 2013

Première publication (Estimation)

12 juin 2013

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

13 juillet 2018

Dernière mise à jour soumise répondant aux critères de contrôle qualité

12 juillet 2018

Dernière vérification

1 juillet 2018

Plus d'information

Termes liés à cette étude

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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