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

20 de março de 2015 atualizado 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.

Visão geral do estudo

Status

Concluído

Condições

Intervenção / Tratamento

Descrição detalhada

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 estudo

Intervencional

Inscrição (Real)

150

Estágio

  • Fase 2

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Locais de estudo

  • 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

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

18 anos e mais velhos (Adulto, Adulto mais velho)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Descrição

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.

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Tratamento
  • Alocação: Randomizado
  • Modelo Intervencional: Atribuição Paralela
  • Mascaramento: Quadruplicar

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
Experimental: 1
Participants will be randomized to receive ALT-836.
Medicamento: 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.
Outros nomes:
  • Formerly TNX-832; Sunol-cH36
Comparador de Placebo: 2
Patients will be randomized to receive placebo.
Medicamento: 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.

O que o estudo está medindo?

Medidas de resultados primários

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

Medidas de resultados secundários

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

Colaboradores e Investigadores

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

Altor BioScience

Colaboradores

National Heart, Lung, and Blood Institute (NHLBI)

Investigadores

  • Cadeira de estudo: Hing C Wong, PhD, Altor BioScience

Publicações e links úteis

A pessoa responsável por inserir informações sobre o estudo fornece voluntariamente essas publicações. Estes podem ser sobre qualquer coisa relacionada ao estudo.

Publicações Gerais

Links úteis

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo

1 de abril de 2009

Conclusão Primária (Real)

1 de outubro de 2012

Conclusão do estudo (Real)

1 de janeiro de 2013

Datas de inscrição no estudo

Enviado pela primeira vez

8 de abril de 2009

Enviado pela primeira vez que atendeu aos critérios de CQ

8 de abril de 2009

Primeira postagem (Estimativa)

10 de abril de 2009

Atualizações de registro de estudo

Última Atualização Postada (Estimativa)

10 de abril de 2015

Última atualização enviada que atendeu aos critérios de controle de qualidade

20 de março de 2015

Última verificação

1 de março de 2015

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

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

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

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