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

20 de marzo de 2015 actualizado por: 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.

Descripción general del estudio

Estado

Terminado

Condiciones

Intervención / Tratamiento

Descripción detallada

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.

Tipo de estudio

Intervencionista

Inscripción (Actual)

150

Fase

  • Fase 2

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

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

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

18 años y mayores (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

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 de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: Aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Cuadruplicar

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: 1
Participants will be randomized to receive ALT-836.
Droga: 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.
Otros nombres:
  • Formerly TNX-832; Sunol-cH36
Comparador de placebos: 2
Patients will be randomized to receive placebo.
Droga: 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.

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Periodo de tiempo
Safety profile of the study drug
Periodo de tiempo: Throughout the 28 days following treatment
Throughout the 28 days following treatment
Number of ventilator-free days at Day 28
Periodo de tiempo: Determined at Day 28
Determined at Day 28

Medidas de resultado secundarias

Medida de resultado
Periodo de tiempo
Mortality at Day 7, 14, 21, 28 and 60
Periodo de tiempo: Determined at Day 7, 14, 21, 28 and 60
Determined at Day 7, 14, 21, 28 and 60
Length of hospitalization at Day 28
Periodo de tiempo: Determined at Day 28
Determined at Day 28
Length of ICU stay at Day 28
Periodo de tiempo: Determined at Day 28
Determined at Day 28
Number of Non-pulmonary organ failure free days at Day 28
Periodo de tiempo: Determined at Day 28
Determined at Day 28
Changes in physiological variables of lung injury
Periodo de tiempo: Throughout the 28 days following treatment
Throughout the 28 days following treatment
Changes in disease severity and lung injury scores
Periodo de tiempo: 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)
Periodo de tiempo: Determined at Day 28
Determined at Day 28
Pharmacokinetics & Pharmacodynamics
Periodo de tiempo: Throughout the 28 days following treatment
Throughout the 28 days following treatment
Immunogenicity
Periodo de tiempo: Throughout the 28 days following treatment
Throughout the 28 days following treatment

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Altor BioScience

Colaboradores

National Heart, Lung, and Blood Institute (NHLBI)

Investigadores

  • Silla de estudio: Hing C Wong, PhD, Altor BioScience

Publicaciones y enlaces útiles

La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.

Publicaciones Generales

Enlaces Útiles

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio

1 de abril de 2009

Finalización primaria (Actual)

1 de octubre de 2012

Finalización del estudio (Actual)

1 de enero de 2013

Fechas de registro del estudio

Enviado por primera vez

8 de abril de 2009

Primero enviado que cumplió con los criterios de control de calidad

8 de abril de 2009

Publicado por primera vez (Estimar)

10 de abril de 2009

Actualizaciones de registros de estudio

Última actualización publicada (Estimar)

10 de abril de 2015

Última actualización enviada que cumplió con los criterios de control de calidad

20 de marzo de 2015

Última verificación

1 de marzo de 2015

Más información

Términos relacionados con este estudio

Palabras clave

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

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

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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