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

Sponsor
Altor BioScience (Industry)
Overall Status
Completed
CT.gov ID
NCT00879606
Collaborator
National Heart, Lung, and Blood Institute (NHLBI) (NIH)
150
Enrollment
20
Locations
2
Arms
45
Duration (Months)
7.5
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease Intervention/Treatment Phase
Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
150 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, 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
Study Start Date :
Apr 1, 2009
Actual Primary Completion Date :
Oct 1, 2012
Actual Study Completion Date :
Jan 1, 2013

Arms and Interventions

Arm Intervention/Treatment
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 Names:
  • 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.

    Outcome Measures

    Primary Outcome Measures

    1. Safety profile of the study drug [Throughout the 28 days following treatment]

    2. Number of ventilator-free days at Day 28 [Determined at Day 28]

    Secondary Outcome Measures

    1. Mortality at Day 7, 14, 21, 28 and 60 [Determined at Day 7, 14, 21, 28 and 60]

    2. Length of hospitalization at Day 28 [Determined at Day 28]

    3. Length of ICU stay at Day 28 [Determined at Day 28]

    4. Number of Non-pulmonary organ failure free days at Day 28 [Determined at Day 28]

    5. Changes in physiological variables of lung injury [Throughout the 28 days following treatment]

    6. Changes in disease severity and lung injury scores [Throughout the 28 days following treatment]

    7. Effects of the study drug and the etiology of the disease (i.e. pulmonary or extra-pulmonary origin) [Determined at Day 28]

    8. Pharmacokinetics & Pharmacodynamics [Throughout the 28 days following treatment]

    9. Immunogenicity [Throughout the 28 days following treatment]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Locations

    Site City State Country Postal Code
    1 Los Angeles County and USC Medical Center Los Angeles California United States 90033
    2 UC Davis Medical Center Sacramento California United States 95817
    3 Stanford University Stanford California United States 94305
    4 Yale University New Haven Connecticut United States 06520
    5 Northwestern University Chicago Illinois United States 60611
    6 West Suburban Hospital Medical Center Oak Park Illinois United States 60302
    7 Illinois Lung and Critical Care Institute Peoria Illinois United States 61606
    8 University of Iowa Iowa City Iowa United States 52246
    9 Kentucky Lung Clinic Hazard Kentucky United States 41701
    10 University of Louisville-Division of Pulmonary and Critical Care Louisville Kentucky United States 40202
    11 Baystate Medical Center Springfield Massachusetts United States 01199
    12 Saint Luke's Hospital Kansas City Missouri United States 64111
    13 Saint Louis University St. Louis Missouri United States 63110
    14 Mercy Hospital St. Louis St. Louis Missouri United States 63141
    15 Mount Sinai Medical Center New York City New York United States 10029
    16 Memorial Sloan-Kettering Cancer Center New York New York United States 10065
    17 Carolinas Medical Center Charlotte North Carolina United States 28203
    18 Piedmont Respiratory Research Foundation Greensboro North Carolina United States 27310
    19 Wake Forest University Winston-Salem North Carolina United States 27157
    20 University of Oklahoma Oklahoma City Oklahoma United States 73104

    Sponsors and Collaborators

    • Altor BioScience
    • National Heart, Lung, and Blood Institute (NHLBI)

    Investigators

    • Study Chair: Hing C Wong, PhD, Altor BioScience

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Altor BioScience
    ClinicalTrials.gov Identifier:
    NCT00879606
    Other Study ID Numbers:
    • CA-ALT-836-01-08
    • NHLBI/NIH-5R44HL082397-03
    First Posted:
    Apr 10, 2009
    Last Update Posted:
    Apr 10, 2015
    Last Verified:
    Mar 1, 2015
    Keywords provided by Altor BioScience
    Sepsis
    Acute Lung Injury
    Acute Respiratory Distress Syndrome
    ALI/ARDS
    Lung Disease
    Additional relevant MeSH terms:
    Sepsis
    Respiratory Distress Syndrome
    Respiratory Distress Syndrome, Newborn
    Acute Lung Injury
    Lung Injury
    Syndrome
    Wounds and Injuries

    Study Results

    No Results Posted as of Apr 10, 2015