Randomized, Double-blind, Placebo-controlled, Parallel-group, Dose-ranging Study to Investigate the MRI Efficacy and the Safety of Six Months' Administration of Firategrast (150 - 1200mg twice daily) in Subjects with Relapsing-Remitting Multiple Sclerosis
- Conditions
- Multiple sclerosisMedDRA version: 14.1Level: PTClassification code 10028245Term: Multiple sclerosisSystem Organ Class: 10029205 - Nervous system disordersTherapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2006-002633-20-IT
- Lead Sponsor
- GlaxoSmithKline Research & Development Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 350
1.Written informed consent
2.Males or females, aged 18 to 65, inclusive
3.A diagnosis of relapsing-remitting MS with dissemination in time and space
4.EDSS of between 0 and 6.0 inclusive at the Screening visit
5.Occurrence of at least two relapses in previous 24 months with at least one relapse or documented evidence of gadolinium-enhancement on MRI (prior to screening) in the previous 12 months. Subject must not have had a relapse within 4 weeks prior to Screening.
6.A minimum of five T2 lesions on brain MRI at Visit 2 as determined by the central MRI analysis reader
7.A female subject is eligible to enter the study if she is:
?Of non-childbearing potential, i.e. women who:
?have documented evidence of tubal ligation, bilateral oophorectomy or hysterectomy; or
?are post-menopausal, defined as at least one year without menses in the absence of hormone replacement therapy. In questionable cases, menopausal status will be confirmed by oestradiol and FSH levels consistent with menopause according to local laboratory ranges. Oestrogen-containing hormone replacement therapies are not allowed during the study.
?Of childbearing potential, has a negative urine pregnancy test at Screening, and agrees to the consistent and correct use of one of the methods of contraception listed below. Subjects will use this contraceptive method for at least one month prior to Screening and should continue to use the same contraceptive method throughout the study until at least 3 days after the last dose of investigational product.
?Progesterone-only oral contraceptives or implants (inserted at least one month prior to Screening, but not beyond the third successive year following insertion) plus an additional barrier method of contraception (condom, diaphragm, cervical cap) during intercourse. Oestrogen-containing contraceptives are not allowed during the study.
?Intra-uterine device (IUD) inserted by a qualified clinician. The IUD must have published data showing that the highest expected failure rate is less than 1% per year.
?Spermicide in conjunction with either a diaphragm, cervical cap or condom.
?Male partner sterilization (vasectomy) prior to female subject's entry into the study and is the sole partner for that female subject
Are the trial subjects under 18? no
Number of subjects for this age range: 0
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
1.Subjects receiving corticosteroids within 4 weeks of Screening for treatment of MS. If non-systemic steroids are being used for other chronic inflammatory conditions, subjects may be included at the discretion of the investigator after discussion with the GSK medical monitor
2.Use of an -interferon product, glatiramer acetate or azathioprine within 3 months of Screening, or use of Mitoxantrone within 12 months of Screening. Subjects who have received other therapies affecting the immune system (such as intravenous immunoglobulin (IVIg), cyclophosphamide, plasmapheresis, or any other immunosuppressive or immunomodulatory treatment) in the past may be included on a case by case basis after discussion with the GSK medical monitor. None of these treatments will be allowed during this study
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 (including known allergy to gadolinium)
5.Use of 4-aminopyridine, rosiglitazone, pioglitazone or any drug that is an inhibitor of or a substrate (with a low therapeutic index) for OATP at Screening. See Section 5.6.2.
6.Patients with clinically significant renal laboratory values: subjects with a calculated creatinine clearance <60ml/min (by Cockcroft and Gault) at Screening
7.Presence of clinically significant hepatic laboratory values: ALT, AST, GGT > 2.0- times the upper limit of normal (ULN); total bilirubin > 1.5 times the ULN at Screening
8.CD4 count <500, CD4:CD8 <1.0, JC viremia detected in plasma or white cells, idiopathic CD4/CD8 lymphopenia or secondary lymphopenia at Screening
9.Any findings on the MRI of the brain at Visit 2 other than MS, except for benign findings that (in the opinion of the central MRI reading site and local site investigator) require no further evaluation or treatment and do not impact patient's neurological health (e.g., small arachnoid cysts, venous angiomas)
10.Current or history of cancer, excluding localized non-melanoma skin cancer
11.Uncontrolled or any active bacterial, viral, or fungal infection at Screening. Any previous serious infections should be discussed with the GSK medical monitor (e.g. opportunistic or atypical infections)
12.History of tuberculosis (TB) or positive chest X-ray for TB at Screening (prior chest X-ray is acceptable if performed within previous 6 months)
13.Known congenital or acquired immunodeficiency
14.Any abnormality on 12-lead ECG at Screening which is clinically significant in the opinion of the investigator
15.Subjects with positive hepatitis B surface antigen, hepatitis C antibody, or HIV tests at Screening
16.Women who are lactating, pregnant (positive pregnancy test at Screening), or planning to become pregnant during the course of the study
17.Recent history or suspicion of current drug abuse (including analgesic abuse) or alcohol abuse within the last 6 months prior to Screening
18.Use of an investigational drug for condition other than MS within 30 days or five half lives (whichever is longer) preceding Screening. Prior use of an investigational drug for MS should be discussed with the GSK medical monitor
19.Any concurrent illness, disability or clinically significant abnormality (including laboratory tests) that may affect the interpretation of clinical efficacy or safety data or p
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method