A Randomized, Double-Blind, Placebo-Controlled Evaluation of the Safety, Efficacy, and Pharmacokinetics of Multiple Doses of Basiliximab, with Concomitant Corticosteroids, in Steroid-Refractory Ulcerative Colitis - BSX-001

• Register: EUCTR
• Last refreshed on: 13 March 2017
• Main ID: EUCTR2006-004303-19-SK
• Date of registration: 08/03/2007
• Prospective Registration: Yes
• Primary sponsor: Cerimon Pharmaceuticals, Inc.
• Public title: A Randomized, Double-Blind, Placebo-Controlled Evaluation of the Safety, Efficacy, and Pharmacokinetics of Multiple Doses of Basiliximab, with Concomitant Corticosteroids, in Steroid-Refractory Ulcerative Colitis - BSX-001
• Scientific title: A Randomized, Double-Blind, Placebo-Controlled Evaluation of the Safety, Efficacy, and Pharmacokinetics of Multiple Doses of Basiliximab, with Concomitant Corticosteroids, in Steroid-Refractory Ulcerative Colitis - BSX-001
• Date of first enrolment: 04/05/2007
• Target sample size: 181
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-004303-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Czech Republic, Slovakia, United Kingdom

Key inclusion & exclusion 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 performed no more than 3 days prior to day of randomization (Day -2 to Day 0, with randomization on Day 1). At the time of endoscopy, a rectal biopsy will be obtained and reviewed by a local pathologist to confirm histopathology compatible with the diagnosis of ulcerative colitis. Randomization can proceed without the screening biopsy result if a previous biopsy result compatible with ulcerative colitis is documented and available in the subject’s medical record.
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:
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. History of partial colectomy or total proctocolectomy
5. 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
6. Initiation of oral aminosalicylate treatment , or change of dose, or
discontinuation less than 4 weeks before study entry
7. Rectally administered medications containing corticosteroids or
aminosalicylates within 2 weeks before screening endoscopy
8. If currently taking a nonsteroidal anti-inflammatory agent (NSAID), the
inability to discontinue NSAID use during study participation
9. Intolerance or inability to continue oral corticosteroids during the trial
10. Stool studies that show presence of ova and parasites, significant
bacterial pathogens, or C. difficile toxin
11. Baseline endoscopic finding of disease isolated to the rectum (proctitis), fistulas, strictures, skip areas, or small bowel inflammation not consistent with backwash ileitis, or findings of multiple epithelial granulomas on biopsy
12. Presence of toxic megacolon
13. 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 <10.5 g/dL
14. Laboratory values as follows:
-Hemoglobin <8.5 g/dL
-WBC <3.0 x 10E9/L
-Neutrophils <1.5 x 10E9 /L
-Lymphocytes <0.5 x 10E9 /L
-Platelets <100 x 10E9 /L
-AST (SGOT) >3 times upper limit of normal
-ALT (SGPT) >3 times upper limit of normal
15. Pregnant or breast-feeding female patients
16. Chest radiograph abnormalities consistent with an infectious process
17. HIV infection
18 Known viral Hepatitis B or C infection
19. History of or exposure to tuberculosis within 6 months before study entry
20. History of central nervous system demyelinating disorder
21. History of colonic dysplasia
22. 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
23. 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
24. Any ECG abnormalities unless approved by the Medical Monitor
25. Treatment with an investigational drug or device within 30 days before
study entry
26. Treatment with an investigational biologic within 6 months before study
entry



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Steroid-refractory ulcerative colitis
MedDRA version: 8.1 Level: LLT Classification code 10009900 Term: Colitis ulcerative

Intervention(s)

Trade Name: Simulect


Product Name: Basiliximab
Pharmaceutical Form: Powder for infusion*
Other descriptive name: Basiliximab
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Powder for infusion*
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

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
• Use of rescue medication
• Hospitalization or colectomy
• Concomitant steroid use (median dose over time and cumulative dose)

Secondary ID(s)

2006-004303-19-GB

BSX - 001