relapsing forms of multiple sclerosis MedDRA version: 9.1 Level: LLT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis MedDRA version: 9.1 Level: LLT Classification code 10063400 Term: Secondary progressive multiple sclerosis
Conditions
Interventions
Product Name: firategrast (USAN approved name)
Product Code: SB-683699
Pharmaceutical Form: Tablet
CAS Number: 402567-16-2
Current Sponsor code: SB-683699
Other descriptive name: firategrast (USAN app
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 2. Male or female, age 18 to 65. 3. A diagnosis of a relapsing form of MS [As per McDonald, 2001; Polman, 2005], with dissemination in time and space. 4. Expanded Disability Status Scale (EDSS) score of between 0 and 6.5 inclusive. 5. Occurrence of at least one clinical attack in the previous 24 months, but not within the 4 weeks prior to Screening or prior to the Baseline Visit. 6. A minimum of two T2 lesions on brain MRI at Screening, as determined by the central MRI analysis reader. 7. A female subject is eligible to enter the study if she is: a. Of non-childbearing potential OR b. Of childbearing potential, has a negative urine pregnancy test at Screening and Baseline, and agrees to consistent and correct use the method of contraception as per the protocol 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) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Subjects receiving corticosteroids within 4 weeks of Screening for treatment of MS. 2. Use of a beta-interferon product, glatiramer acetate or azathioprine within 3 months of Screening, or use of Mitoxantrone within 12 months of Screening. 3. Previous exposure to alemtuzumab, natalizumab or firategrast administration, bone marrow transplantation or whole body irradiation. 4. Subjects with a cardiac pacemaker or any other type of metal implant or with any other contraindication for MRI. 5. Use of 4-aminopyridine, rosiglitazone, pioglitazone or any drug that is an inhibitor of or a substrate (with a low therapeutic index) for Organic Anion Transporter Protein (OATP). 6. Subjects with clinically significant renal laboratory values: subjects with a calculated creatinine clearance 2 times the upper limit of the reference range; total bilirubin > 1.5 the upper limit of the normal range. 9. CD4 count < 500, CD4:CD8 < 1.0, JCV viremia in plasma or white cells, idiopathic CD4/CD8 lymphopenia or secondary lymphopenia at Screening. 10. Any findings at Screening on the MRI of the brain other than MS, except for benign findings. 11. Uncontrolled or any active bacterial, viral, or fungal infection. 12. History of tuberculosis (TB) or positive chest X-ray for TB at Screening. 13. Known congenital or acquired immunodeficiency. 14. Current or history of cancer, excluding localized non-melanoma skin cancer. 15. Any abnormality on 12-lead Electrocardiogram (ECG) at Screening. 16. Positive hepatitis B surface antigen, hepatitis C antibody or HIV tests at Screening. 21. Contraindications to lumbar puncture.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary aims of this study are 1) to determine, for a sample of subjects with relapsing forms of MS, the number and change from baseline in the number of leukocytes and the CD4:CD8 ratio in the CSF and blood up to the completion of 24-weeks of dosing with firategrast and 2) to assess the number and change from the end of treatment (and baseline) in the number of leukocytes and the CD4:CD8 ratio in the CSF and blood in the 12-week period following treatment with firategrast. These objectives will be assessed through the use of descriptive statistics only. ;Secondary Objective: • To determine the number and change in number of total leukocytes, total lymphocytes and lymphocyte subsets and the CD4:CD8 ratio in the CSF and blood during and after treatment with firategrast. Lymphocyte subsets: T-lymphocytes: CD4+, CD8+ B-lymphocytes: CD19+ • To examine blood for mobilization of CD34+ early hematopoietic progenitor cells from the bone marrow during and after treatment with firategrast. • To explore the relationship between changes in the number of leukocytes in the CSF and blood. • To explore the relationship between systemic exposure to firategrast and the metabolite, GW786375X, and changes in leukocyte counts in the CSF and blood. • To determine firategrast and GW786375X levels in CSF. • To explore potential relationships between genetic variants and response to firategrast, pharmacokinetic endpoints and bilirubin levels. • To investigate the safety and tolerability of up to six months' administration of firategrast. ;Primary end point(s): The primary outcome measures are the number and change in number of total leukocytes, total lymphocytes and lymphocyte subsets (CD4+ and CD8+ T-lymphocytes, CD19+ B-lymphocytes, CD34+ early hematopoietic progenitor cells) and the CD4:CD8 ratio in the CSF and/or blood. The time points of interest for all of the above endpoints are Baseline, Treatment Week 4 (CD34+ early hematopoietic progenitor cells in blood o | — |
Countries
Belgium, Czech Republic, Denmark, Sweden
Outcome results
None listed