Randomised, 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

• Register: EUCTR
• Last refreshed on: 18 April 2012
• Main ID: EUCTR2006-002633-20-LT
• Date of registration: 05/07/2007
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Research & Development Ltd
• Public title: Randomised, 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
• 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 Firategrast (150 – 1200mg twice daily) in Subjects with Relapsing-Remitting Multiple Sclerosis
• Date of first enrolment: 07/09/2007
• Target sample size: 350
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-002633-20
• 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

Countries of recruitment

Austria, Finland, France, Germany, Italy, Lithuania, Netherlands, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Written informed consent
2. Males or females, aged 18 to 65, inclusive
3. Diagnosis of RRMS 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 1 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. 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 or has a negative urine pregnancy test at Screening, and agrees to the consistent and correct use of agreed methods of contraception.
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:
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 a beta-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.
6. Patients with clinically significant renal laboratory values: subjects with a calculated creatinine clearance <60ml/min (by Cockcroft and Gault) at Screening
7. Subjects with local urinalysis findings of 1) proteinuria, defined as greater than or equal to 1+ protein, on urine dipstick or 2) renal tubular cell casts or 3) greater than or equal to 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.
8. 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
9. CD4 count <500, CD4:CD8 <1.0, JC viremia detected in plasma or white cells, idiopathic CD4/CD8 lymphopenia or secondary lymphopenia at Screening
10. 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)
11. Current or history of cancer, excluding localized non-melanoma skin cancer
12. 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)
13. 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)
14. Known congenital or acquired immunodeficiency
15. Any abnormality on 12-lead ECG at Screening which is clinically significant in the opinion of the investigator
16. Subjects with positive hepatitis B surface antigen, hepatitis C antibody, or HIV tests at Screening
17. Women who are lactating, pregnant (positive pregnancy test at Screening), or planning to become pregnant during the course of the study
18. Recent history or suspicion of current drug abuse (including analgesic abuse) or alcohol abuse within the last 6 months prior to Screening
19. Use of an investigational drug for condition other than MS within 30 days or five half lives (which

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

Health Condition(s) or Problem(s) studied

Relapsing-Remitting Multiple Sclerosis
MedDRA version: 8.1 Level: LLT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis

Intervention(s)

Product Name: Firategrast
Product Code: SB683699
Pharmaceutical Form: Tablet
CAS Number: 402567-16-2
Current Sponsor code: SB683699
Other descriptive name: Firategrast (USAN approved name)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: Firategrast
Product Code: SB683699
Pharmaceutical Form: Tablet
CAS Number: 402567-16-2
Current Sponsor code: SB683699
Other descriptive name: Firategrast (USAN approved name)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): The primary endpoint is the cumulative number of new gadolinium-enhancing lesions on monthly MRI scans. MRI is an accepted surrogate marker of MS burden of disease for exploratory trials.

Main Objective: • To investigate the MRI efficacy of six months' administration of Firategrast in subjects with relapsing-remitting MS

Secondary Objective: To investigate the effect on the following parameters of 6 months' administration of Firategrast in subjects with relapsing-remitting MS:
- safety and tolerability
- dose-response relationship
- relationship between efficacy endpoints and systemic exposure to Firategrast and the metabolite GW786375X
- interaction between systemic exposure to Firategrast and systemic exposure to i.v. methylprednisolone during relapses
- potential relationships between genetic variants and response to Firategrast, PK endpoints, and bilirubin levels
- MS clinical scores
- fatigue and employment status
- utility of the Multiple Sclerosis Impact Scale (MSIS-29) in clinical trials

Secondary ID(s)

A4M105038

2006-002633-20-NL