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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Altor Bioscience Corporation
ClinicalTrials.gov Identifier:
NCT00879606
First received: April 8, 2009
Last updated: January 14, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Sepsis
Acute Lung Injury
Acute Respiratory Distress Syndrome
Drug: ALT-836
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Efficacy and Safety Evaluation of ALT-836 in Patients With Sepsis and Acute Lung Injury/Acute Respiratory Distress Syndrome

Resource links provided by NLM:


Further study details as provided by Altor Bioscience Corporation:

Primary Outcome Measures:
  • Safety profile of the study drug [ Time Frame: Throughout the 28 days following treatment ] [ Designated as safety issue: Yes ]
  • Number of ventilator-free days at Day 28 [ Time Frame: Determined at Day 28 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Mortality at Day 7, 14, 21, 28 and 60 [ Time Frame: Determined at Day 7, 14, 21, 28 and 60 ] [ Designated as safety issue: No ]
  • Length of hospitalization at Day 28 [ Time Frame: Determined at Day 28 ] [ Designated as safety issue: No ]
  • Length of ICU stay at Day 28 [ Time Frame: Determined at Day 28 ] [ Designated as safety issue: No ]
  • Number of Non-pulmonary organ failure free days at Day 28 [ Time Frame: Determined at Day 28 ] [ Designated as safety issue: No ]
  • Changes in physiological variables of lung injury [ Time Frame: Throughout the 28 days following treatment ] [ Designated as safety issue: No ]
  • Changes in disease severity and lung injury scores [ Time Frame: Throughout the 28 days following treatment ] [ Designated as safety issue: No ]
  • Effects of the study drug and the etiology of the disease (i.e. pulmonary or extra-pulmonary origin) [ Time Frame: Determined at Day 28 ] [ Designated as safety issue: No ]
  • Pharmacokinetics & Pharmacodynamics [ Time Frame: Throughout the 28 days following treatment ] [ Designated as safety issue: No ]
  • Immunogenicity [ Time Frame: Throughout the 28 days following treatment ] [ Designated as safety issue: Yes ]

Enrollment: 150
Study Start Date: April 2009
Estimated Study Completion Date: March 2014
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Participants will be randomized to receive ALT-836.
Drug: 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.
Other Name: Formerly TNX-832; Sunol-cH36
Placebo Comparator: 2
Patients will be randomized to receive placebo.
Drug: 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.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00879606

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

Additional Information:
No publications provided by Altor Bioscience Corporation

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Altor Bioscience Corporation
ClinicalTrials.gov Identifier: NCT00879606     History of Changes
Other Study ID Numbers: CA-ALT-836-01-08, NHLBI/NIH-5R44HL082397-03
Study First Received: April 8, 2009
Last Updated: January 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Altor Bioscience Corporation:
Sepsis
Acute Lung Injury
Acute Respiratory Distress Syndrome
ALI/ARDS
Lung Disease

Additional relevant MeSH terms:
Acute Lung Injury
Lung Injury
Respiratory Distress Syndrome, Adult
Respiratory Distress Syndrome, Newborn
Sepsis
Syndrome
Disease
Infant, Newborn, Diseases
Infant, Premature, Diseases
Infection
Inflammation
Lung Diseases
Pathologic Processes
Respiration Disorders
Respiratory Tract Diseases
Systemic Inflammatory Response Syndrome
Thoracic Injuries
Wounds and Injuries

ClinicalTrials.gov processed this record on November 20, 2014