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

20 maart 2015 bijgewerkt door: 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.

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

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.

Studietype

Ingrijpend

Inschrijving (Werkelijk)

150

Fase

  • Fase 2

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

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

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

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.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Verviervoudigen

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: 1
Participants will be randomized to receive ALT-836.
Geneesmiddel: 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.
Andere namen:
  • Formerly TNX-832; Sunol-cH36
Placebo-vergelijker: 2
Patients will be randomized to receive placebo.
Geneesmiddel: 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.

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Tijdsspanne
Safety profile of the study drug
Tijdsspanne: Throughout the 28 days following treatment
Throughout the 28 days following treatment
Number of ventilator-free days at Day 28
Tijdsspanne: Determined at Day 28
Determined at Day 28

Secundaire uitkomstmaten

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

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Altor BioScience

Medewerkers

National Heart, Lung, and Blood Institute (NHLBI)

Onderzoekers

  • Studie stoel: Hing C Wong, PhD, Altor BioScience

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Algemene publicaties

Nuttige links

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 april 2009

Primaire voltooiing (Werkelijk)

1 oktober 2012

Studie voltooiing (Werkelijk)

1 januari 2013

Studieregistratiedata

Eerst ingediend

8 april 2009

Eerst ingediend dat voldeed aan de QC-criteria

8 april 2009

Eerst geplaatst (Schatting)

10 april 2009

Updates van studierecords

Laatste update geplaatst (Schatting)

10 april 2015

Laatste update ingediend die voldeed aan QC-criteria

20 maart 2015

Laatst geverifieerd

1 maart 2015

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

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

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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