- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00879606
Anti-TF Antibody (ALT-836) to Treat Septic Patients With Acute Lung Injury or Acute Respiratory Distress Syndrome
March 20, 2015 updated by: 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.
Study Overview
Status
Completed
Intervention / Treatment
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 Type
Interventional
Enrollment (Actual)
150
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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California
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Los Angeles, California, United States, 90033
- Los Angeles County and USC Medical Center
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Sacramento, California, United States, 95817
- UC Davis Medical Center
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Stanford, California, United States, 94305
- Stanford University
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Connecticut
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New Haven, Connecticut, United States, 06520
- Yale University
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Illinois
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Chicago, Illinois, United States, 60611
- Northwestern University
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Oak Park, Illinois, United States, 60302
- West Suburban Hospital Medical Center
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Peoria, Illinois, United States, 61606
- Illinois Lung and Critical Care Institute
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Iowa
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Iowa City, Iowa, United States, 52246
- University of Iowa
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Kentucky
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Hazard, Kentucky, United States, 41701
- Kentucky Lung Clinic
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Louisville, Kentucky, United States, 40202
- University of Louisville-Division of Pulmonary and Critical Care
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Massachusetts
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Springfield, Massachusetts, United States, 01199
- Baystate Medical Center
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Missouri
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Kansas City, Missouri, United States, 64111
- Saint Luke's Hospital
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St. Louis, Missouri, United States, 63110
- Saint Louis University
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St. Louis, Missouri, United States, 63141
- Mercy Hospital St. Louis
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New York
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New York, New York, United States, 10065
- Memorial Sloan-Kettering Cancer Center
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New York City, New York, United States, 10029
- Mount Sinai Medical Center
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North Carolina
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Charlotte, North Carolina, United States, 28203
- Carolinas Medical Center
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Greensboro, North Carolina, United States, 27310
- Piedmont Respiratory Research Foundation
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Winston-Salem, North Carolina, United States, 27157
- Wake Forest University
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Oklahoma
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Oklahoma City, Oklahoma, United States, 73104
- University of Oklahoma
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
INCLUSION CRITERIA:
- Suspected or proven infection
- Hypoxemia: PaO2/FiO2is ≤300 mm Hg
- Bilateral infiltrates consistent with pulmonary edema
- Positive-pressure mechanical ventilation through an endotracheal tube
- No clinical evidence of left atrial hypertension to explain bilateral infiltrates
- 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:
- <18 years
- Inability to obtain consent
- Patient, surrogate, or physician not committed to full support
- Moribund state in which death was perceived to be imminent
- Morbid obesity
- Malignancy or other irreversible disease or condition for which 6-month mortality is estimated to be >50%
- Known HIV positive with known end stage processes
- Prior cardiac arrest requiring CPR without fully demonstrated neurological recovery; or New York Heart Association Class IV
- Pregnant or nursing
- ALI/ARDS induced by mechanical or chemical injury directly to the lung (including burns, trauma, and near drowning)
- >48 hours since all inclusion criteria are met
- Neuromuscular disease that impairs ability to ventilate without assistance
- Severe chronic respiratory disease, severe pulmonary hypertension, or ventilator dependency
- Chest wall deformity resulting in severe exercise restriction, secondary polycythemia, or respirator dependent
- History of organ transplant (including bone marrow)
- Severe chronic liver disease, as determined by a Child-Pugh Score >10
- Hemoglobin persistently < 7.0 g/dL
- Platelet count <50,000/mm3
- Prolonged INR >3
- Bleeding disorders unless corrective surgery has been performed
- Active internal bleeding
- 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.
- Diffuse alveolar hemorrhage from vasculitis
- Known bleeding diathesis
- 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
- Stroke within 3 months of study entry
- Trauma with an increased risk of life-threatening bleeding
- A history of severe head trauma that required hospitalization, or intracranial surgery within two months of study entry
- Any history of intracerebral arteriovenous malformation, cerebral aneurysm, or central nervous system mass lesion
- 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.
- Participation in another experimental medication study within 30 days of study entry.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: 1
Participants will be randomized to receive ALT-836.
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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:
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Placebo Comparator: 2
Patients will be randomized to receive placebo.
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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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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Safety profile of the study drug
Time Frame: Throughout the 28 days following treatment
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Throughout the 28 days following treatment
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Number of ventilator-free days at Day 28
Time Frame: Determined at Day 28
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Determined at Day 28
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Mortality at Day 7, 14, 21, 28 and 60
Time Frame: Determined at Day 7, 14, 21, 28 and 60
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Determined at Day 7, 14, 21, 28 and 60
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Length of hospitalization at Day 28
Time Frame: Determined at Day 28
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Determined at Day 28
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Length of ICU stay at Day 28
Time Frame: Determined at Day 28
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Determined at Day 28
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Number of Non-pulmonary organ failure free days at Day 28
Time Frame: Determined at Day 28
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Determined at Day 28
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Changes in physiological variables of lung injury
Time Frame: Throughout the 28 days following treatment
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Throughout the 28 days following treatment
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Changes in disease severity and lung injury scores
Time Frame: Throughout the 28 days following treatment
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Throughout the 28 days following treatment
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Effects of the study drug and the etiology of the disease (i.e. pulmonary or extra-pulmonary origin)
Time Frame: Determined at Day 28
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Determined at Day 28
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Pharmacokinetics & Pharmacodynamics
Time Frame: Throughout the 28 days following treatment
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Throughout the 28 days following treatment
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Immunogenicity
Time Frame: Throughout the 28 days following treatment
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Throughout the 28 days following treatment
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Study Chair: Hing C Wong, PhD, Altor BioScience
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
April 1, 2009
Primary Completion (Actual)
October 1, 2012
Study Completion (Actual)
January 1, 2013
Study Registration Dates
First Submitted
April 8, 2009
First Submitted That Met QC Criteria
April 8, 2009
First Posted (Estimate)
April 10, 2009
Study Record Updates
Last Update Posted (Estimate)
April 10, 2015
Last Update Submitted That Met QC Criteria
March 20, 2015
Last Verified
March 1, 2015
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Infections
- Respiratory Tract Diseases
- Respiration Disorders
- Lung Diseases
- Systemic Inflammatory Response Syndrome
- Inflammation
- Disease
- Infant, Newborn, Diseases
- Infant, Premature, Diseases
- Thoracic Injuries
- Sepsis
- Syndrome
- Wounds and Injuries
- Respiratory Distress Syndrome
- Respiratory Distress Syndrome, Newborn
- Acute Lung Injury
- Lung Injury
Other Study ID Numbers
- CA-ALT-836-01-08
- NHLBI/NIH-5R44HL082397-03
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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