Study Of SB-683699 Compared To Placebo In Subjects With Relapsing-Remitting Multiple Sclerosis (MS)

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00395317
• Date of registration: 01/11/2006
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline
• Public title: Study Of SB-683699 Compared To Placebo In Subjects With Relapsing-Remitting Multiple Sclerosis (MS)
• Scientific title: Randomised, Double-blind, Placebo-controlled, Parallel-group, Dose-ranging Study to Investigate the MRI Efficacy and the Safety of Six Months Administration of SB-683699 in Subjects With Relapsing-Remitting Multiple Sclerosis
• Date of first enrolment: December 2006
• Target sample size: 343
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00395317
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
• Phase: Phase 2

Countries of recruitment

Australia, Austria, Canada, Finland, France, Germany, Italy, Lithuania, Netherlands, New Zealand, Norway, Poland, Russian Federation, Spain, United Kingdom

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion criteria

Inclusion criteria:

- Written informed consent

- Males or females, aged 18 to 65, inclusive

- A diagnosis of relapsing-remitting MS [Polman, 2005; McDonald, 2001] with
dissemination in time and space

- EDSS of between 0 and 6.0 inclusive at the Screening visit

- 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. In addition, subjects experiencing a relapse between Screen and Visit 3
will not be eligible to be randomized.

- A minimum of five T2 lesions on brain MRI at Visit 2 as determined by the central MRI
analysis reader

- 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). 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

- In France, a subject will be eligible for inclusion in this study only if either
affiliated to or a beneficiary of a social security category.

Exclusion Criteria:

- 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

- Use of an b-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

- Previous exposure to alemtuzumab, natalizumab or firategrast administration, bone
marrow transplantation or whole body irradiation

- Subjects with a cardiac pacemaker or any other type of metal implant or with any
other contraindication for MRI (including known allergy to gadolinium)

- 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.

- Subjects with clinically significant renal laboratory values: subjects with a
calculated creatinine clearance <60ml/min (by Cockcroft and Gault) at Screening

- Subjects with local urinalysis findings of 1) proteinuria, defined as =1+ protein,
on urine dipstick or 2) renal tubular cell casts or 3) =5 red blood cells / high
power field will be excluded from the study if the result is still present on a
repeat urinalysis during the screening period.

- 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

- CD4 count <500, CD4:CD8 <1.0 (if result still present on a repeat test during the
screening period), JC viremia detected in plasma or white cells, idiopathic CD4/CD8
lymphopenia or secondary lymphopenia at Screening

- 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)

- Current or history of cancer, excluding localized non-melanoma skin cancer

- 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)

- 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)

- Known congenital or acquired immunodeficiency

- Any abnormality on 12-lead ECG at Screening which is clinically significant in the
opinion of the investigator

- Subjects with positive hepatitis B surface antigen, hepatitis C antibody, or HIV
tests at Screening

- Women who are lactating, pregnant (positive pregnancy test at Screening), or planning
to become pregnant during the course of the study

- Recent history or suspicion of current drug abuse (including analgesic abuse) or
alcohol abuse within the last 6 months prior to Screening

- 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

- Any concurrent illness, disability or clinically significant abnormality (including
labor


Age minimum: 18 Years
Age maximum: 65 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Multiple Sclerosis

Intervention(s)

Drug: Firategrast 150 mg

Other: Placebo

Drug: Firategrast 300 mg

Primary Outcome(s)

Cumulative number of new gadolinium-enhancing lesions on monthly MRI scans during the Treatment Phase [Time Frame: Baseline and 24 weeks]

Secondary Outcome(s)

Relapses Occurring during the On-Treatment Phase [Time Frame: Baseline and 24 weeks]

Change from Baseline in Expanded Disability Status Scale (EDSS) scores [Time Frame: Baseline and 24 weeks]

Cumulative number of new/newly enlarging T2 lesions on MRI scans [Time Frame: Baseline and 24 weeks]

Cumulative number of persistent gadolinium-enhancing lesions on monthly MRI scans [Time Frame: Baseline and 24 weeks]

Cumulative volume of new gadolinium-enhancing lesions on monthly MRI scans [Time Frame: Baseline and 24 weeks]

Cumulative number of new T1 hypointense lesions on MRI scans [Time Frame: Baseline and 24 weeks]

Cumulative number of total enhancing lesions on monthly MRI scans: the sum of new and persistent gadolinium-enhancing lesions [Time Frame: Baseline and 24 weeks]

Change from Baseline in Multiple Sclerosis Functional Composite (MSFC)scores [Time Frame: Baseline and 24 weeks]

Secondary ID(s)

A4M105038

Source(s) of Monetary Support

Please refer to primary and secondary sponsors