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Anti-TF Antibody (ALT-836) to Treat Septic Patients With Acute Lung Injury or Acute Respiratory Distress Syndrome

20 mars 2015 mis à jour par: Altor BioScience

Efficacy and Safety Evaluation of ALT-836 in Patients With Sepsis and Acute Lung Injury/Acute Respiratory Distress Syndrome

This is a prospective, randomized (1:1), double-blind, multi-center, Phase II clinical study to test the safety and efficacy of a recombinant chimeric anti-tissue factor antibody (ALT-836) versus placebo in patients with sepsis and acute lung injury/acute respiratory distress syndrome (ALI/ARDS). This study was divided into two parts and the first part of the study has been completed. In the first part of the study, sixty patients were randomized at a 1:1 ratio to receive one dose of the study drug or placebo. In the second part of the study, ninety patients will be randomized at a 1:1 ratio to receive a multi-dose treatment regimen of single doses every 72 hours up to a maximum of 4 doses of the study drug or placebo, provided there are no safety concerns.

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Description détaillée

Tissue factor (TF)-dependent procoagulant activity and associated inflammatory processes may play a role in the severity and progression of ALI/ARDS. Recent studies demonstrated that TF levels were elevated in plasma and pulmonary edema fluid of ARDS/ALI patients compared to control patients with hydrostatic pulmonary edema. These higher plasma TF levels were correlated with increased mortality, fewer ventilation-free days, the presence of disseminated intravascular coagulation and the presence of sepsis in patients with ALI/ARDS, suggesting that systemic activation of coagulation may be clinically important in ALI/ARDS. Moreover, the pulmonary TF levels in patients with ALI/ARDS were found to range between 0.5 and 2 nM, approximately 100-fold higher than simultaneous plasma levels, suggesting an intra-alveolar source of TF. Thus, anti-TF antibody blockage of TF activity may therefore provide an effective therapeutic mechanism for the treatment of inflammatory disorders such as ALI and ARDS. This study will test the hypothesis that administration of anti-TF antibody (ALT-836) to septic patients with ALI/ARDS will improve the clinical outcome by shortening the duration of mechanical ventilation for these patients.

Type d'étude

Interventionnel

Inscription (Réel)

150

Phase

  • Phase 2

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

  • États-Unis
    • California
      • Los Angeles, California, États-Unis, 90033
        • Los Angeles County and USC Medical Center
      • Sacramento, California, États-Unis, 95817
        • UC Davis Medical Center
      • Stanford, California, États-Unis, 94305
        • Stanford University
    • Connecticut
      • New Haven, Connecticut, États-Unis, 06520
        • Yale University
    • Illinois
      • Chicago, Illinois, États-Unis, 60611
        • Northwestern University
      • Oak Park, Illinois, États-Unis, 60302
        • West Suburban Hospital Medical Center
      • Peoria, Illinois, États-Unis, 61606
        • Illinois Lung and Critical Care Institute
    • Iowa
      • Iowa City, Iowa, États-Unis, 52246
        • University of Iowa
    • Kentucky
      • Hazard, Kentucky, États-Unis, 41701
        • Kentucky Lung Clinic
      • Louisville, Kentucky, États-Unis, 40202
        • University of Louisville-Division of Pulmonary and Critical Care
    • Massachusetts
      • Springfield, Massachusetts, États-Unis, 01199
        • Baystate Medical Center
    • Missouri
      • Kansas City, Missouri, États-Unis, 64111
        • Saint Luke's Hospital
      • St. Louis, Missouri, États-Unis, 63110
        • Saint Louis University
      • St. Louis, Missouri, États-Unis, 63141
        • Mercy Hospital St. Louis
    • New York
      • New York, New York, États-Unis, 10065
        • Memorial Sloan-Kettering Cancer Center
      • New York City, New York, États-Unis, 10029
        • Mount Sinai Medical Center
    • North Carolina
      • Charlotte, North Carolina, États-Unis, 28203
        • Carolinas Medical Center
      • Greensboro, North Carolina, États-Unis, 27310
        • Piedmont Respiratory Research Foundation
      • Winston-Salem, North Carolina, États-Unis, 27157
        • Wake Forest University
    • Oklahoma
      • Oklahoma City, Oklahoma, États-Unis, 73104
        • University of Oklahoma

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 et plus (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

INCLUSION CRITERIA:

  1. Suspected or proven infection
  2. Hypoxemia: PaO2/FiO2is ≤300 mm Hg
  3. Bilateral infiltrates consistent with pulmonary edema
  4. Positive-pressure mechanical ventilation through an endotracheal tube
  5. No clinical evidence of left atrial hypertension to explain bilateral infiltrates
  6. Presence of at least three of the four SIRS criteria. If only two criteria are evidenced, one must be temperature or WBC

Criteria 2 and 3 must occur within a 24-hour interval. The 48-hour enrollment time window begins when criteria 2, 3, and 4 are met.

EXCLUSION CRITERIA:

  1. <18 years
  2. Inability to obtain consent
  3. Patient, surrogate, or physician not committed to full support
  4. Moribund state in which death was perceived to be imminent
  5. Morbid obesity
  6. Malignancy or other irreversible disease or condition for which 6-month mortality is estimated to be >50%
  7. Known HIV positive with known end stage processes
  8. Prior cardiac arrest requiring CPR without fully demonstrated neurological recovery; or New York Heart Association Class IV
  9. Pregnant or nursing
  10. ALI/ARDS induced by mechanical or chemical injury directly to the lung (including burns, trauma, and near drowning)
  11. >48 hours since all inclusion criteria are met
  12. Neuromuscular disease that impairs ability to ventilate without assistance
  13. Severe chronic respiratory disease, severe pulmonary hypertension, or ventilator dependency
  14. Chest wall deformity resulting in severe exercise restriction, secondary polycythemia, or respirator dependent
  15. History of organ transplant (including bone marrow)
  16. Severe chronic liver disease, as determined by a Child-Pugh Score >10
  17. Hemoglobin persistently < 7.0 g/dL
  18. Platelet count <50,000/mm3
  19. Prolonged INR >3
  20. Bleeding disorders unless corrective surgery has been performed
  21. Active internal bleeding
  22. Major surgery within 24 hours before study drug infusion, or evidence of active bleeding postoperatively, or plan for any major surgery within 3 days after study drug infusion.
  23. Diffuse alveolar hemorrhage from vasculitis
  24. Known bleeding diathesis
  25. Presence of an epidural catheter or lumbar puncture within 48 hours before study drug infusion or anticipation of receiving an epidural catheter or a lumbar puncture within 48 hours after study drug infusion
  26. Stroke within 3 months of study entry
  27. Trauma with an increased risk of life-threatening bleeding
  28. A history of severe head trauma that required hospitalization, or intracranial surgery within two months of study entry
  29. Any history of intracerebral arteriovenous malformation, cerebral aneurysm, or central nervous system mass lesion
  30. Uses of certain medications or treatment regimens such as chemotherapy, unfractionated heparin, low-molecular-weight heparin, Warfarin, antithrombin III, acetylsalicylic acid, glycoprotein IIb/IIIa antagonists, thrombolytic therapy, and activated Protein C are restricted.
  31. Participation in another experimental medication study within 30 days of study entry.

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: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Quadruple

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: 1
Participants will be randomized to receive ALT-836.
Médicament: ALT-836
In the first part of this study, recombinant chimeric anti-tissue factor antibody ALT-836 was administered as a single dose (0.06 mg/Kg) via intravenous infusion over 15 minutes. In the second part of this study, up to four doses (0.06 mg/Kg) of ALT-836 will be administered via intravenous infusion over 15 minutes.
Autres noms:
  • Formerly TNX-832; Sunol-cH36
Comparateur placebo: 2
Patients will be randomized to receive placebo.
Médicament: Placebo
In the first part of this study, a single dose of Placebo was administered via intravenous infusion over 15 minutes. In the second part of this study, up to four doses of Placebo will be administered via intravenous infusion over 15 minutes.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Délai
Safety profile of the study drug
Délai: Throughout the 28 days following treatment
Throughout the 28 days following treatment
Number of ventilator-free days at Day 28
Délai: Determined at Day 28
Determined at Day 28

Mesures de résultats secondaires

Mesure des résultats
Délai
Mortality at Day 7, 14, 21, 28 and 60
Délai: Determined at Day 7, 14, 21, 28 and 60
Determined at Day 7, 14, 21, 28 and 60
Length of hospitalization at Day 28
Délai: Determined at Day 28
Determined at Day 28
Length of ICU stay at Day 28
Délai: Determined at Day 28
Determined at Day 28
Number of Non-pulmonary organ failure free days at Day 28
Délai: Determined at Day 28
Determined at Day 28
Changes in physiological variables of lung injury
Délai: Throughout the 28 days following treatment
Throughout the 28 days following treatment
Changes in disease severity and lung injury scores
Délai: Throughout the 28 days following treatment
Throughout the 28 days following treatment
Effects of the study drug and the etiology of the disease (i.e. pulmonary or extra-pulmonary origin)
Délai: Determined at Day 28
Determined at Day 28
Pharmacokinetics & Pharmacodynamics
Délai: Throughout the 28 days following treatment
Throughout the 28 days following treatment
Immunogenicity
Délai: Throughout the 28 days following treatment
Throughout the 28 days following treatment

Collaborateurs et enquêteurs

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

Parrainer

Altor BioScience

Collaborateurs

National Heart, Lung, and Blood Institute (NHLBI)

Les enquêteurs

  • Chaise d'étude: Hing C Wong, PhD, Altor BioScience

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Publications générales

Liens utiles

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

1 avril 2009

Achèvement primaire (Réel)

1 octobre 2012

Achèvement de l'étude (Réel)

1 janvier 2013

Dates d'inscription aux études

Première soumission

8 avril 2009

Première soumission répondant aux critères de contrôle qualité

8 avril 2009

Première publication (Estimation)

10 avril 2009

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Estimation)

10 avril 2015

Dernière mise à jour soumise répondant aux critères de contrôle qualité

20 mars 2015

Dernière vérification

1 mars 2015

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • CA-ALT-836-01-08
  • NHLBI/NIH-5R44HL082397-03

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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