Ulcerative Colitis
Conditions
Keywords
Pediatric UC, Adacolumn apheresis
Brief summary
Children aged up to 18 years with moderately active Ulcerative Colitis (PUCAI:35-64) will receive one weekly Adacolumn® apheresis treatment over 5 consecutive weeks, followed by up to 3 optional Adacolumn® apheresis treatments over 3 consecutive weeks. Primary end point is PUCAI at Week 12. The main part of the clinical investigation will be continued by a one year follow up for responders.
Detailed description
The individual clinical investigation period will be 12 weeks per patient. If the patient will take part in the follow up, the individual clinical investigation period will be 64 weeks. Patients receive one weekly Adacolumn® apheresis over 5 consecutive weeks. The treating investigator may decide to add up to 3 treatments based on his judgment. Treatment details Day -07: Screening; Day 00 Baseline: 1st Adacolumn® apheresis; Day 07: 2nd Adacolumn® apheresis; Day 14: 3rd Adacolumn® apheresis; Day 21: 4th Adacolumn® apheresis; Day 28: 5th Adacolumn® apheresis; Week 12:Final evaluation
Interventions
DEVICEAdacolumn®
The medical device Adacolumn® (CE-Mark Certificate G1 07 01 366 76013) is an adsorptive type extracorporeal apheresis column. It has been shown to effectively improve clinical and endoscopic signs and symptoms in UC in adults by removing granulocytes and monocytes and by changing the Cytokine production.
Sponsors
Otsuka Frankfurt Research Institute GmbH
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 18 Years
Healthy volunteers
No
Inclusion criteria
1. Children and adolescents \< 18 years 2. Ulcerative colitis documented by clinical symptoms, endoscopic findings and histology (in patient history) 3. Moderate active ulcerative colitis at baseline evaluation, defined as follows:PUCAI between 35 and 64 4. Pancolitis or left-sided colitis 5. Ulcerative colitis for at least 3 months 6. Receiving or having received one or more of the following medicinal products before screening: * Sulfasalazine, mesalamine and other 5-aminosalicylic acid (5-ASA) agents for 4 weeks or more with a stable dose for the last 2 weeks, * 0.5mg/kg/body weight with a maximum of 20 mg per day of prednisone with a stable dose for the last 2 weeks, or * 6-mercaptopurine or azathioprine for 12 weeks or more with a stable dose for the last 4 weeks Other UC medication is not allowed (see also Chapter 4.4.2). 7. For female patients of child-bearing potential, a negative pregnancy test and agreement to use an effective contraceptive method or abstain from sexual activities during the course of the clinical investigation 8. Agreement to participate in all visits 9. Signed written informed consent document by patients and their legal guardian or representative 10. Body weight must be more or equal 30kg 11. Adequate peripheral venous access to allow for completion of the apheresis treatments
Exclusion criteria
1. Febrile (\>38ºC) 2. Evidence of toxic megacolon 3. Anticipated need for surgery within 12 weeks after Day 00 4. Major surgery within the past 6 weeks 5. Known obstructive diseases of the gastrointestinal system 6. Proctocolectomy, total colectomy, ileostomy, stoma or ileal pouch-anal anastomosis 7. A history of allergic reaction to heparin or heparin-induced thrombocytopenia 8. A history of hypersensitivity reaction associated with an apheresis procedure or intolerance of apheresis procedures 9. Known infection with enteric pathogens, pathogenic ova or parasites, or a positive assay for C. difficile toxin 10. Symptomatic hypotension 11. Pediatric heart conditions and problems at high susceptibility for thrombotic events (e.g. valve defects or similar) 12. A history of physical findings compatible with a cerebrovascular accident 13. Prosthetic heart valve, pacemaker or other permanent implant 14. Severe cardiovascular or peripheral vascular disease 15. Liver disease defined as levels of GOT \[AST\], GPT \[ALT\] or alkaline phosphatase \>2.5x the upper limit of the normal range for the laboratory performing test 16. History of cirrhosis 17. Renal insufficiency, defined as serum creatinine \>150% of the upper limit of the normal range for the laboratory performing the test 18. Known bleeding disorder (PT or PTT\>1.5x the upper limit of the normal range for the laboratory performing the test), or concomitant anticoagulant therapy for purposes other than apheresis treatment 19. Prior history suggestive of a hypercoagulable disorder, including 1 or more episodes of pulmonary embolism or deep vein thrombosis 20. Known infection with Hepatitis B or C, or HIV 21. Abnormal hematology parameters defined as severe anemia with hemoglobin \<8.5g/dL, white blood cell count of \<3,500/μl and a granulocyte count \<2,000/μl 22. Fibrinogen level \>700mg/dL 23. Infection: * Active infections from successful completion of antibiotic treatment for routine bacterial infection less than 4 weeks of entry into the clinical investigation (screening) * Febrile viral infection within 4 weeks of entry into the clinical investigation (screening) * Less than 12 weeks from conclusion of therapy for systemic fungal infections to screening 24. Malignancy within the past 2 years other than surgically cured skin carcinoma or cervical dysplasia (CIN I-II) 25. History of dysplasia or carcinoma of the colon 26. Current drug or alcohol abuse 27. Pregnant, lactating or planning to become pregnant during the course of the clinical investigation 28. Used within the last 30 days an investigational medicinal product, biologic or device 29. Pre-treatment of UC with drugs other than 5-ASA and derivatives, azathioprine and or corticosteroids, e.g. immunosuppressants and biologics 30. Steroid-resistance or -dependency, defined as inability to completely withdraw steroids without inducing a relapse or flare-up of the disease 31. Topical therapy for ulcerative colitis within the last 2 weeks.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary response variable: Changes in mean PUCAI between baseline and Week 12 | 12 Weeks plus 1 year Follow up |
Secondary
| Measure | Time frame |
|---|---|
| Difference in Endoscopic Activity Index (EAI) according to Rachmilewitz between Week 12 and baseline for those patients with 2 endoscopies | Week 12 |
Outcome results
None listed