Pilot/Ph I Safety and Efficacy of ODSH in Protein Losing Enteropathy Secondary to Single Ventricle Palliative Surgery

• Status: Terminated
• Trial end date: 2012-02-01
• Target enrollment: 0
• Participant gender: All

Summary

Protein Losing Enteropathy (PLE) is a serious medical condition that may develop in children and adults with congenital heart disease for which a palliative procedure known as the "Fontan procedure" has been performed. The loss of serum proteins into the gastrointestinal tract that is associated with PLE can cause serious symptoms and life-threatening complications. A number of clinical studies have suggested that heparin administration can have clinical benefit in children with PLE, however the risk of bleeding associated with the administration of heparin is an important concern and commonly limits its administration. ODSH is a desulfated heparin with minimal anticoagulation properties but which, in pre-clinical studies, appears to have the potential to replace heparin and greatly reduce the risk of bleeding. This open label study is to assess the safety and evidence of therapeutic effect of the administration of ODSH as a 4-day continuous intravenous infusion in patients with an exacerbation of their PLE.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Cantex Pharmaceuticals; Chimerix

Criteria

Inclusion Criteria:

1. Male or female ≥ 6 years old.

2. History of single ventricle palliative surgery.

3. Anticipated need for four or more days of hospitalization, in the investigator's judgment, for the treatment of exacerbation of PLE.

Clinically significant PLE is defined as the presence of clinically significant symptoms (including, but not limited to, diarrhea, abdominal pain, peripheral edema and/or ascites), AND increased fecal alpha 1-antitrypsin (FA1AT; > 200 mg/dl) OR hypoalbuminemia of < 3 gr/dL; requiring supplemental albumin infusions.

4. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) not higher than 1.25 times the ULN for age.

5. Platelet count of > 80,000 per mm3, hemoglobin of > 9.5 g/dL.

6. The adult subject or the underage subject/legal guardian is willing to provide informed consent and to comply with the study procedures.

7. Female subject of childbearing potential who is not pregnant, and is not lactating and is not planning to become pregnant during the study and will use medically acceptable contraception method for the duration of the study.

Exclusion Criteria:

1. Has congenital or acquired hematologic disease or coagulation disorder.

2. Has other type of PLE not associated with single ventricle palliative surgery e.g. subjects with congenital defects of glycation or with Crohn's disease; congenital trypsinogen or enterokinase deficiency;

3. Has a clinical need for prophylactic or therapeutic treatment with oral or parenteral anticoagulant medications within 72 hours from the start of ODSH treatment or during the study. [The use of antithrombotic agents such as acetyl salicylic acid for cardiovascular prophylaxis or clopidogrel (or similar drug class agents) is permitted].

4. Has documented liver failure or a serum ALT or AST greater than 1.5 times the upper limit of normal, or total bilirubin greater than 1.5 the upper limit of normal;

5. Has clinically significant proteinuria or severe renal failure based on a creatinine clearance < 30 mL/min calculated from plasma creatinine (Appendix B) with the Cockcroft-Gault formula for adults or with any of the recommended formulas for subjects 6 to 18 years old;

6. Has active gastrointestinal ulcer disease or evidence of gastrointestinal bleeding or urinary tract bleeding or any other source of bleeding within 60 days of the Screening visit.

7. History of HIV, hepatitis B or hepatitis C; and

8. Major surgery, stroke or myocardial infarction within the past 60 days from screening. Subjects with recent minor surgery can be enrolled in the study.