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

Phase 2

Completed

Conditions: Acute Respiratory Distress Syndrome
Sepsis
Acute Lung Injury

Interventions: Drug: Placebo
Drug: ALT-836

Registration Number: NCT00879606

Lead Sponsor: Altor BioScience

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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 150

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2	Placebo	Patients will be randomized to receive placebo.
1	ALT-836	Participants will be randomized to receive ALT-836.

Primary Outcome Measures

Name	Time	Method
Safety profile of the study drug	Throughout the 28 days following treatment
Number of ventilator-free days at Day 28	Determined at Day 28

Secondary Outcome Measures

Name	Time	Method
Length of hospitalization at Day 28	Determined at Day 28
Immunogenicity	Throughout the 28 days following treatment
Number of Non-pulmonary organ failure free days at Day 28	Determined at Day 28
Mortality at Day 7, 14, 21, 28 and 60	Determined at Day 7, 14, 21, 28 and 60
Effects of the study drug and the etiology of the disease (i.e. pulmonary or extra-pulmonary origin)	Determined at Day 28
Length of ICU stay at Day 28	Determined at Day 28
Changes in physiological variables of lung injury	Throughout the 28 days following treatment
Changes in disease severity and lung injury scores	Throughout the 28 days following treatment
Pharmacokinetics & Pharmacodynamics	Throughout the 28 days following treatment

Trial Locations

Locations (20): Los Angeles County and USC Medical Center
🇺🇸
Los Angeles, California, United States
UC Davis Medical Center
🇺🇸
Sacramento, California, United States
Stanford University
🇺🇸
Stanford, California, United States
Northwestern University
🇺🇸
Chicago, Illinois, United States
West Suburban Hospital Medical Center
🇺🇸
Oak Park, Illinois, United States
Illinois Lung and Critical Care Institute
🇺🇸
Peoria, Illinois, United States
Kentucky Lung Clinic
🇺🇸
Hazard, Kentucky, United States
University of Iowa
🇺🇸
Iowa City, Iowa, United States
University of Louisville-Division of Pulmonary and Critical Care
🇺🇸
Louisville, Kentucky, United States
Saint Luke's Hospital
🇺🇸
Kansas City, Missouri, United States
Mount Sinai Medical Center
🇺🇸
New York City, New York, United States
Saint Louis University
🇺🇸
St. Louis, Missouri, United States
Mercy Hospital St. Louis
🇺🇸
St. Louis, Missouri, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸
New York, New York, United States
Piedmont Respiratory Research Foundation
🇺🇸
Greensboro, North Carolina, United States
Carolinas Medical Center
🇺🇸
Charlotte, North Carolina, United States
Wake Forest University
🇺🇸
Winston-Salem, North Carolina, United States
University of Oklahoma
🇺🇸
Oklahoma City, Oklahoma, United States
Baystate Medical Center
🇺🇸
Springfield, Massachusetts, United States
Yale University
🇺🇸
New Haven, Connecticut, United States