A Study Designed to Evaluate ODSH in Subjects With Exacerbations of COPD (COPD)

An Open-Label Phase Followed by a Randomized, Double-Blind, Placebo-Controlled Phase in a Study Designed to Evaluate Intravenous 2-O, 3-O Desulfated Heparin (ODSH) in Subjects With Exacerbations of Chronic Obstructive Pulmonary Disease

The purpose of this study is to determine whether ODSH, when added to conventional treatment, is more effective in treating COPD exacerbations than conventional therapy alone.

Study Overview

• Status: Terminated
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Open-Label; Drug: Placebo Comparator: Placebo-Control Arm 0.9% Sodium Chloride; Drug: ODSH

Detailed Description

The management of acute exacerbations of COPD today is qualitatively the same as it was 40 years ago: bronchodilators, corticosteroids, and antibiotics. Because of the prominent pathophysiological role of neutrophils in exacerbations of COPD, neutrophils and their toxic oxidants and proteases represent therapeutic targets which are currently unchallenged in the treatment of this aspect of the disease. Ideally, to disrupt neutrophilic airway inflammation, one would both block neutrophilic influx from the vascular space into the airway, as well as neutralize or inactivate prominent neutrophilic toxins such as the proteases HLE and cathepsin G.

Heparin is a sulfated mucopolysaccharide that slows blood clot formation by inhibiting the reactions that lead to formation of fibrin clots. Physicians use heparin to prevent blood clot formation during open-heart surgery, bypass surgery and dialysis. Heparin also prevents previously formed clots from becoming larger and causing more serious problems. Heparin has other biological properties, most notably anti-inflammatory activity. At doses required to be therapeutically beneficial as an anti-inflammatory, heparin can cause severe, potentially life-threatening hemorrhage. ParinGenix has chemically modified heparin to retain the anti-inflammatory activity while reducing anti-coagulant properties.

Heparin has long been known to be a potent inhibitor, both in vitro and in vivo, of the cationic neutrophil proteases HLE and cathepsin G. However, heparin also has numerous other important anti-inflammatory effects. P-selectin is the primary endothelial attachment molecule mediating neutrophil rolling along the vessel wall. At concentrations close to those achieved in plasma near the high range of therapeutic anticoagulation, heparin inhibits P-selectin and P-selectin mediated interaction of leukocytes with endothelium. Heparin also blocks the leukocyte integrin Mac-1 (CD11b/CD18) and Mac-1-dependent leukocyte adherence to endothelial ICAM. These combined effects on rolling, integrin-dependent attachment and perhaps other aspects of cellular passage through the basement membrane prevent neutrophil accumulation in areas of inflammation. As an example, when given in much higher concentrations than those appropriate for therapeutic anticoagulation, heparin efficiently blocks neutrophilic influx into ischemic reperfused myocardium and brain reducing the size of both myocardial infarction and ischemic stroke. Thus, heparin and heparin analogues may have the potential to also reduce inflammatory influx of neutrophils into the airway during exacerbations of COPD.

All subjects will receive standard of care treatment, including corticosteroids, beta-2 agonists, and antibiotics as well as ODSH or placebo.

• Study Type: Interventional
• Enrollment (Actual): 158
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • University Hospital Gasthuisberg
  • Liege, Belgium, 4000
    • CHU Liege Domain Universitaire du Sart Tilman
  • Yvior, Belgium, 5530
    • Cliniques Universiaries U.C.L. de Mont-Gondinne
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta Hospital
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 1T2
      • Kelowna General Hospital
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Vancouver Coastal Health
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2H 2A6
      • St. Boniface General Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • QE II Health Sciences Centre
  • Ontario
    • Mississauga, Ontario, Canada
      • Credit Valley Hospital,
    • Ottawa, Ontario, Canada, K1Y 4E9
      • The Ottawa Hospital, Civic Campus
    • Toronto, Ontario, Canada, H2X-2P4
      • University of Toronto
  • Quebec
    • Quebec City, Quebec, Canada, G1V 4G5
      • Laval Hospital
• Germany
  • Gerlingen, Germany, 70839
    • Klinik Schillerhohe
  • Grosshansdorf, Germany, 22927
    • Pneumologisches Forschungsinstitut GmbH
  • Hannover, Germany, 30625
    • Medizinsche Hochschule
  • Mainz, Germany, 55101
    • Uniklinikum Mainz
  • Munchen, Germany, 80336
    • Klinikum der LMU Innenstadt
• Poland
  • Czestochowa, Poland, 42-200
    • Wojewodzki Szpital Specjalistyczny im. Najswietszej Marii Panny
  • Katowice, Poland, 40-752
    • Samodzielny Publiczny Szpital Kliniczny SUM w Katowicach
  • Krakow, Poland, 31-202
    • Krakowski Szpital Specjalistyczny Im. Jana Pawla Ii
  • Lodz, Poland, 90-153
    • Samodzielny Publiczny ZOZ, Uniwersytecki Szpital Liniczny nr 1 im Norberta Barlickiego
  • Lublin, Poland, 20-718
    • Wojewodzki Szpital Specjalistyczny im. Stefana Kardynala Wyszynskiego, Samodzielny Publiczny Zespol Opieki Zdrowotnej
  • Lublin, Poland, 20-954
    • Samodzielny Publiczny Szpital Klinczny nr 4 W Lublinie
  • Olawa, Poland, 55-200
    • Zespol Opieki Zdrowotnej w Olawie
  • Poznan, Poland, 60-569
    • Wieklopolskie Centrum Chorob Pluc i Gruzlicy
  • Warszawa, Poland, 04-749
    • Miedzyleski Szpital Specjalistyczny w Warszawie
  • Warszawa, Poland, 01-138
    • I Klinika Chorob Plus, Instyut Gruzlicy i Chorob Pluc
  • Wroclaw, Poland, 50-417
    • Akademicki Szpital Kliniczny im. Jana Mikulicza-Radeckiego
• United States
  • California
    • Orange, California, United States, 92868
      • Pulmonary Consultants & Primary Care
  • Georgia
    • Marietta, Georgia, United States, 30060
      • WellStar Kennestone Hospital
  • Louisiana
    • Shreveport, Louisiana, United States, 71130
      • Louisiana State University Health Sciences Center in Shreveport
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington Universtiy school of Medicine
  • Oregon
    • Portland, Oregon, United States, 97220
      • The Oregon Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University of the Commonwealth of Higher Education
  • Texas
    • Houston, Texas, United States, 77030
      • Michael E. DeBakey VA Medical Center
    • Houston, Texas, United States, 77030
      • Methodist Hospital
    • Tyler, Texas, United States, 75708
      • University of Texas Health Care Center at Tyler
  • Washington
    • Everett, Washington, United States, 98201
      • Western Washington Medical Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male and female patients (40 years of age or older) with an established diagnosis of COPD based upon medical history who are being admitted to the hospital to treat an exacerbation of COPD;
2. Normal prothrombin time and activated partial thromboplastin time; Platelet count; hemoglobin and hematocrit

Exclusion Criteria:

1. Certain diseases such as:

   • asthma;
   • left heart failure or pulmonary embolism;
   • lung cancer;
   • pneumonia
   • liver or kidney disease
   • blood clotting disorder
   • Positive HIV or hepatitis tests
   • GI bleeding, physical trauma with bleeding, any disease with bleeding within 60 days of study entry

2. Certain medications such as:

   • Plavix®
   • Warfarin
   • Heparin therapy
   • Certain antibiotics
3. Exacerbations that are too severe (requiring intubation and mechanical ventilation)
4. Women of child-bearing potential, pregnancy or breast-feeding
5. Unable or unwilling to provide informed consent and follow study procedures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Open Label; Initial six subjects treated with ODSH open-label to confirm safety in subjects with an acute exacerbation of COPD; six additional patients will be enrolled following safety review.	Drug: Open-Label; ODSH administered open-label; Other Names: PGX-100
Placebo Comparator: 0.9% Sodium Chloride; Placebo Comparator: Placebo-Control Arm 0.9% Sodium Chloride Solution bolus; dose of 0.375mg/kg/hr over 96 hours.	Drug: Placebo Comparator: Placebo-Control Arm 0.9% Sodium Chloride; Placebo-Control Arm: Bolus infusion followed by a 96 hour continuous infusion of 0.9%Sodium Chloride; Other Names: 0.9% Sodium Chloride Solution Placebo-Control Arm
Active Comparator: Randomized, Blinded, ODSH Arm; Subjects will receive standard of care treatment. ODSH is administered in bolus doses estimated to inhibit inflammatory mediators randomized 1:1 to ODSH 8mg/kg or placebo. The continuous infusion dose will be 0.375 mg/kg/hr over 96 hours.	Drug: ODSH; Randomized, Blinded, ODSH Arm; Other Names: PGX-100

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment Failure	The primary outcome of the study is "Treatment Failure" as defined by Failure to discharge from hospital based on GOLD (Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease) criteria or relapse after DC from hospital.	Time to hospital discharge and 21 days post-treatment, up to 31 days

Collaborators and Investigators

• Sponsor: Chimerix
• Investigators: Principal Investigator: Tobias Welte, MD, Hannover Medical School

Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Primary Completion (Actual): August 1, 2009
• Study Completion (Actual): October 1, 2009

Study Registration Dates

• First Submitted: April 6, 2007
• First Submitted That Met QC Criteria: April 6, 2007
• First Posted (Estimate): April 9, 2007

Study Record Updates

• Last Update Posted (Actual): December 2, 2021
• Last Update Submitted That Met QC Criteria: December 1, 2021
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: COPD; Chronic Obstructive Pulmonary Disease; Heparin; ODSH; Exacerbations of COPD
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: PGX-ODSH-2006