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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 uppdaterad av: 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.

Studieöversikt

Status

Avslutad

Betingelser

Intervention / Behandling

Detaljerad beskrivning

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.

Studietyp

Interventionell

Inskrivning (Faktisk)

150

Fas

  • Fas 2

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

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

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år och äldre (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

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.

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: Randomiserad
  • Interventionsmodell: Parallellt uppdrag
  • Maskning: Fyrdubbla

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: 1
Participants will be randomized to receive ALT-836.
Läkemedel: 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.
Andra namn:
  • Formerly TNX-832; Sunol-cH36
Placebo-jämförare: 2
Patients will be randomized to receive placebo.
Läkemedel: 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.

Vad mäter studien?

Primära resultatmått

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

Sekundära resultatmått

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

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

Altor BioScience

Samarbetspartners

National Heart, Lung, and Blood Institute (NHLBI)

Utredare

  • Studiestol: Hing C Wong, PhD, Altor BioScience

Publikationer och användbara länkar

Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.

Allmänna publikationer

Användbara länkar

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart

1 april 2009

Primärt slutförande (Faktisk)

1 oktober 2012

Avslutad studie (Faktisk)

1 januari 2013

Studieregistreringsdatum

Först inskickad

8 april 2009

Först inskickad som uppfyllde QC-kriterierna

8 april 2009

Första postat (Uppskatta)

10 april 2009

Uppdateringar av studier

Senaste uppdatering publicerad (Uppskatta)

10 april 2015

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

20 mars 2015

Senast verifierad

1 mars 2015

Mer information

Termer relaterade till denna studie

Nyckelord

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

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

Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .

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