Steroid-refractory ulcerative colitis MedDRA version: 8.1 Level: LLT Classification code 10009900 Term: Colitis ulcerative
Conditions
Interventions
Trade Name: Simulect
Product Name: Basiliximab
Pharmaceutical Form: Powder for infusion*
Other descriptive name: Basiliximab
Concentration unit: mg milligram(s)
Concentration type: equal
Concentratio
Sponsors
Cerimon Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must satisfy all of the following inclusion criteria to be eligible for the study: 1. Male or female subjects, age =18 years and =75 years 2. Weight of 40 kg or greater 3. Signed a current IRB/IEC-approved informed consent form 4. Diagnosis of ulcerative colitis confirmed through screening endoscopy. A rectal biopsy will be obtained and reviewed by a local pathologist. Histopathology must be compatible with the diagnosis. 5. Extent of disease must involve at least the left colon (i.e., greater than 15 cm beyond the anal verge as the endoscope is withdrawn) 6. Moderate to severe disease, defined as a total Mayo score of 6 points or greater, including an endoscopic subscore of 2 points or greater. Systemic features of tachycardia, fever, and/or significant anemia should not be present 7. Steroid-refractory disease, defined as moderate to severe disease, without systemic features , despite treatment with prednisone 40 – 50 mg/day (or other oral steroid at equivalent dose) orally for a minimum of 14 days immediately preceding study entry 8. Concomitant azathioprine or 6-mercaptopurine treatment is permitted during the study if initiated at least 12 weeks before study entry, and if the dose has not been changed or stopped for at least 8 weeks before study entry. 9. Concomitant oral aminosalicylate treatment is permitted during the study if initiated at least 4 weeks before study entry, and if the dose has not been changed or stopped during this time. 10. Females of childbearing potential must use an effective birth control method, and be willing to continue birth control during the study, and for 4 months after the last dose of study drug. 11. Females of non-childbearing potential should be surgically sterile (bilateral tubal ligation with surgery at least 6 months before study entry, hysterectomy, or bilateral oophorectomy at least 2 months before study entry) or post-menopausal for at least 2 years. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Presence of any of the following conditions will exclude the subject from eligibility for the study: 1. Prior treatment with basiliximab or daclizumab at any time 2. Prior treatment with cyclosporine, tacrolimus, methotrexate, or any anti- TNF agent within 3 months before study entry 3. Prior treatment with parenteral corticosteroids within 14 days before study entry 4. Initiation of azathioprine or 6-mercaptopurine treatment less than 12 weeks before study entry, or discontinuation or change of dose less than 8 weeks before study entry 5. Initiation of oral aminosalicylate treatment , or change of dose, or discontinuation less than 4 weeks before study entry 6. Rectally administered medications containing corticosteroids or aminosalicylates within 2 weeks before screening endoscopy 7. If currently taking a nonsteroidal anti-inflammatory agent (NSAID), the inability to discontinue NSAID use during study participation 8. Intolerance or inability to continue oral corticosteroids during the trial 9. Stool studies that show presence of ova and parasites, significant bacterial pathogens, or C. difficile toxin 10. Colitis that is indeterminate, suggestive of Crohn’s disease, or isolated to the rectum, based on endoscopic and/or biopsy findings 11. Presence of toxic megacolon 12. Severely ill patients as evidenced by greater than 6 episodes of loose stools, all of them bloody, during a 24-hour period within the screening window, concurrent with any of the following systemic features: -Heart rate >90 beats/min at rest -Temperature >37.8 degrees C -Hemoglobin 3 times upper limit of normal -ALT (SGPT) >3 times upper limit of normal 14. Pregnant or breast-feeding female patients 15. Chest radiograph abnormalities consistent with an infectious process 16. Known HIV, or viral Hepatitis B or C infection 17. History of or exposure to tuberculosis within 6 months before study entry 18. History of central nervous system demyelinating disorder 19. History of colonic dysplasia 20. History of malignancy during the previous 5 years or current malignancy, with exception of adequately treated non-melanoma skin cancer or in situ carcinoma of the cervix 21. History of varicella, herpes zoster, or severe viral infection within 6 weeks before study entry, exposure to varicella within 21 days before study entry, or vaccination with live virus within 4 weeks before study entry 22. Any ECG abnormalities unless approved by the Medical Monitor 23. Treatment with an investigational drug or device within 30 days before study entry 24. Treatment with an investigational biologic within 6 months before study entry
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Efficacy: Assess the efficacy, relative to placebo, of 40 mg basiliximab given intravenously, at 2 week intervals for a total of 3 doses, with concomitant oral corticosteroids, in subjects with steroid-refractory, moderate to severe Ulcerative Colitis. A total of 3 doses will be administered during the 8 week duration of the trial. Safety: Evaluate the overall safety of this multiple-dose regimen in this patient population. ;Secondary Objective: Secondary objectives are to assess: • Efficacy, relative to placebo, of basiliximab 20 mg, given with concomitant oral corticosteroids, according to the same schedule • Safety of basiliximab 20 mg multiple-dose regimen • Pharmacokinetics of both basiliximab regimens in this population • Immunogenicity of multiple doses of basiliximab through measurement of formation of antibodies to basiliximab, and monitoring for hypersensitivity reactions ;Primary end point(s): The primary efficacy endpoint will be clinical remission at week 8. Secondary efficacy endpoints will include: • Clinical remission at week 4 • Clinical response at weeks 4 and 8 • Mucosal healing at weeks 4 and 8 • Time to clinical remission • Time to clinical response • Avoidance of rescue medication • Avoidance of hospitalization or colectomy • Concomitant steroid use (median dose over time and cumulative dose) | — |
Countries
Belgium, Czech Republic, Slovakia, United Kingdom
Outcome results
None listed