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

NCT00395317 | Completed Phase 2

• 1 other identifier: A4M105038
• Study Type: interventional
• Target: 343
• Locations: 13 countries
• Sites: 77

Brief Summary

SB-683699 is an oral medication that is thought to reduce the number of active white blood cells entering the brain; these white blood cells are part of the disease process for MS. This study will look at whether different doses of SB-683699 are effective and safe in patients with relapsing remitting MS.

Conditions

Multiple Sclerosis

Keywords

magnetic resonance imaging; multiple sclerosis; SB-683699

Outcome Measures

Primary Outcomes (1)

• Cumulative number of new gadolinium-enhancing lesions on monthly MRI scans during the Treatment Phase

  Baseline and 24 weeks

Secondary Outcomes (8)

• Cumulative volume of new gadolinium-enhancing lesions on monthly MRI scans

  Baseline and 24 weeks

• Cumulative number of persistent gadolinium-enhancing lesions on monthly MRI scans

  Baseline and 24 weeks

• Cumulative number of total enhancing lesions on monthly MRI scans: the sum of new and persistent gadolinium-enhancing lesions

  Baseline and 24 weeks

• Cumulative number of new T1 hypointense lesions on MRI scans

  Baseline and 24 weeks

• Cumulative number of new/newly enlarging T2 lesions on MRI scans

  Baseline and 24 weeks

Study Arms (5)

Arm 1

PLACEBO COMPARATOR

placebo (4 tablets)

Other: Placebo

Arm 2

EXPERIMENTAL

SB-683699 150 mg bid (1 x 150mg + 3 placebo tablets)

Other: Placebo; Drug: Firategrast 150 mg

Arm 3

EXPERIMENTAL

SB-683699 600 mg bid (2 x 300mg + 2 placebo tablets)

Other: Placebo; Drug: Firategrast 300 mg

Arm 4

EXPERIMENTAL

SB-683699 900 mg bid (3 x 300 mg + 1 placebo tablet)

Other: Placebo; Drug: Firategrast 300 mg

Arm 5

EXPERIMENTAL

SB-683699 1200 mg bid, male subjects only (4 x 300 mg tablets)

Drug: Firategrast 300 mg

Interventions

Placebo OTHER

placebo tablet

Arm 1; Arm 2; Arm 3; Arm 4

Firategrast 150 mg DRUG

150 mg tablet

Also known as: SB-683699

Arm 2

Firategrast 300 mg DRUG

300 mg tablet

Also known as: SB-683699

Arm 3; Arm 4; Arm 5

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (79)

GSK Investigational Site

Camperdown, New South Wales, 2050, Australia

Location

GSK Investigational Site

Woodville, South Australia, 5011, Australia

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GSK Investigational Site

Fitzroy, Victoria, 3065, Australia

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GSK Investigational Site

Parkville, Victoria, 3050, Australia

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GSK Investigational Site

Graz, A-8036, Austria

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GSK Investigational Site

Innsbruck, A-6020, Austria

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GSK Investigational Site

London, Ontario, N6A 5C1, Canada

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GSK Investigational Site

Ottawa, Ontario, K1H 8L6, Canada

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GSK Investigational Site

Gatineau, Quebec, J9J 0A5, Canada

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GSK Investigational Site

Greenfield Park, Quebec, J4V 2J2, Canada

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GSK Investigational Site

Turku, 20100, Finland

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GSK Investigational Site

Clermont-Ferrand, 63003, France

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GSK Investigational Site

Dijon, 21033, France

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GSK Investigational Site

Lille, 59000, France

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GSK Investigational Site

Marseille, 13385, France

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GSK Investigational Site

Nantes, 44093, France

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GSK Investigational Site

Rennes, 35033, France

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GSK Investigational Site

Strasbourg, 67091, France

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GSK Investigational Site

Neuburg an der Donau, Bavaria, 86633, Germany

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Hamburg, Hamburg, 22087, Germany

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GSK Investigational Site

Herborn, Hesse, 35745, Germany

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GSK Investigational Site

Achim, Lower Saxony, 28832, Germany

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GSK Investigational Site

Hanover, Lower Saxony, 30625, Germany

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GSK Investigational Site

Rostock, Mecklenburg-Vorpommern, 18147, Germany

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GSK Investigational Site

Bad Honnef, North Rhine-Westphalia, 53604, Germany

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GSK Investigational Site

Bielefeld, North Rhine-Westphalia, 33647, Germany

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GSK Investigational Site

Cologne, North Rhine-Westphalia, 50767, Germany

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GSK Investigational Site

Cologne, North Rhine-Westphalia, 51109, Germany

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GSK Investigational Site

Düren, North Rhine-Westphalia, 52349, Germany

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GSK Investigational Site

Essen, North Rhine-Westphalia, 45122, Germany

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GSK Investigational Site

Dresden, Saxony, 01307, Germany

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GSK Investigational Site

Leipzig, Saxony, 04103, Germany

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GSK Investigational Site

Leipzig, Saxony, 04157, Germany

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GSK Investigational Site

Berlin, State of Berlin, 10625, Germany

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GSK Investigational Site

Berlin, State of Berlin, 10961, Germany

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GSK Investigational Site

Berlin, State of Berlin, 12167, Germany

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GSK Investigational Site

Chieti, Abruzzo, 66013, Italy

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GSK Investigational Site

Rome, Lazio, 00163, Italy

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GSK Investigational Site

Gallarate, Lombardy, 21013, Italy

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GSK Investigational Site

Milan, Lombardy, 20132, Italy

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GSK Investigational Site

Siena, Tuscany, 53100, Italy

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GSK Investigational Site

's-Hertogenbosch, 5211 RW, Netherlands

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GSK Investigational Site

Breda, 4818 CK, Netherlands

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GSK Investigational Site

Eindhoven, 5623 EJ, Netherlands

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GSK Investigational Site

Nieuwegein, 3435 CM, Netherlands

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GSK Investigational Site

Sittard-geleen, 6162 BG, Netherlands

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GSK Investigational Site

Venray, 5801 CE, Netherlands

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GSK Investigational Site

Auckland, 1001, New Zealand

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GSK Investigational Site

Christchurch, 8001, New Zealand

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GSK Investigational Site

Wellington, 6021, New Zealand

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GSK Investigational Site

Bergen, 5021, Norway

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GSK Investigational Site

Drammen, 3004, Norway

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GSK Investigational Site

Hamar, 2317, Norway

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GSK Investigational Site

Sandnes, 4313, Norway

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GSK Investigational Site

Skien, 3710, Norway

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GSK Investigational Site

Gdansk, 80-299, Poland

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GSK Investigational Site

Poznan, 60-479, Poland

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GSK Investigational Site

Poznan, 61-298, Poland

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GSK Investigational Site

Warsaw, 02-097, Poland

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GSK Investigational Site

Moscow, 117049, Russia

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GSK Investigational Site

Moscow, 125101, Russia

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GSK Investigational Site

Moscow, 125367, Russia

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GSK Investigational Site

Saint Petersburg, 194291, Russia

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GSK Investigational Site

Saint Petersburg, 194354, Russia

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GSK Investigational Site

Saint Petersburg, 197022, Russia

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GSK Investigational Site

Saint Petersburg, 197376, Russia

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GSK Investigational Site

Barakaldo (Vizcaya), 48903, Spain

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GSK Investigational Site

Barcelona, 08035, Spain

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GSK Investigational Site

Madrid, 28007, Spain

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GSK Investigational Site

Madrid, 28035, Spain

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GSK Investigational Site

Madrid, 28046, Spain

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GSK Investigational Site

San Sebastián, 20014, Spain

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GSK Investigational Site

Seville, 41071, Spain

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GSK Investigational Site

Valencia, 46010, Spain

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GSK Investigational Site

Romford, Essex, RM7 0AG, United Kingdom

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GSK Investigational Site

Hartshill, Stoke-on-Trent, ST4 7LN, United Kingdom

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GSK Investigational Site

Newcastle upon Tyne, NE1 4LP, United Kingdom

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GSK Investigational Site

Nottingham, NG7 2UH, United Kingdom

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GSK Investigational Site

Sheffield, S10 2JF, United Kingdom

Location

Related Publications (1)

• Miller DH, Weber T, Grove R, Wardell C, Horrigan J, Graff O, Atkinson G, Dua P, Yousry T, Macmanus D, Montalban X. Firategrast for relapsing remitting multiple sclerosis: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2012 Feb;11(2):131-9. doi: 10.1016/S1474-4422(11)70299-X. Epub 2012 Jan 5.

  PMID: 22226929 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Firategrast

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2006
• First Posted: November 2, 2006
• Study Start: December 1, 2006
• Primary Completion: August 1, 2009
• Study Completion: August 1, 2010
• Last Updated: April 9, 2012

Record last verified: 2012-04

Locations

NO (5); AU (4); CA (4); DE (18); IT (5); NZ (3); ES (8); RU (7); NL (6); PL (4); FR (7); FI (1); GB (5)