Study Of White Blood Cells In The Cerebrospinal Fluid And Blood Of Patients With Relapsing Forms Of Multiple Sclerosis

NCT00469378 | Completed Phase 2 DMC

• 1 other identifier: A4M108119
• Study Type: interventional
• Target: 46
• Locations: 5 countries
• Sites: 10

Brief Summary

This is a study to count the number of white blood cells in the cerebrospinal fluid and blood at the beginning and end of treatment with firategrast and at 4 and 12 weeks after stopping firategrast. Cerebrospinal fluid flows through and protects the brain and spinal cord. It is important to understand what happens to the number of white blood cells because they are important in preventing infections.

Conditions

Multiple Sclerosis

Keywords

firategrast; lymphocytes; leukocytes; SB-683699; cerebrospinal fluid; relapsing forms of multiple sclerosis

Outcome Measures

Primary Outcomes (24)

• Assessment of total leukocytes in cerebrospinal fluid (CSF)

  Total leukocyte count in the CSF was done at Baseline (Week 0), Week 24, Week 28 and Week 36. CSF sample data presented are results from the local clinical laboratory.

  Baseline (Week 0), Week 24, 28 and 36

• Change from Baseline in number of total leukocytes in CSF

  Total leukocyte count in the CSF was done at Baseline (Week 0), Week 24, Week 28 and Week 36. CSF sample data presented are results from the local clinical laboratory. Baseline was defined at Week 0. Change from Baseline is the value at indicated time points minus the Baseline value.

  Baseline (Week 0) and Week 24, 28 and 36

• Assessment of total leukocytes in blood

  Total leukocyte count in the blood was done at Baseline (Week 0), Week 4, Week 24, Week 28 and Week 36. Blood sample data presented are results from the independent assessor.

  Baseline (Week 0), Week 4, 24, 28 and 36

• Change from Baseline in number of total leukocytes in blood

  Total leukocyte count in the blood was done at Baseline (Week 0), Week 4, Week 24, Week 28 and Week 36. Blood sample data presented are results from the independent assessor. Baseline was defined at Week 0. Change from Baseline is the value at indicated time points minus the Baseline value.

  Baseline (Week 0) and Week 4, 24, 28, 36

• Assessment of total lymphocytes in CSF

  Total lymphocyte count in the CSF was done at Baseline (Week 0), Week 24, Week 28 and Week 36. All the data presented are based on results from independent assessor.

  Baseline (Week 0), Week 24, 28 and 36

• Change from Baseline in number of total lymphocytes in CSF

  Total lymphocyte count in the CSF was done at Baseline (Week 0), Week 24, Week 28 and Week 36. All the data presented are based on results from independent assessor. Baseline was defined at Week 0. Change from Baseline is the value at indicated time points minus the Baseline value.

  Baseline (Week 0) and Week 24, 28, 36

• Assessment of total lymphocytes in blood

  Total lymphocyte count in the blood was done at Baseline (Week 0), Week 4, Week 24, Week 28 and Week 36. All the data presented are based on results from independent assessor.

  Baseline (Week 0), Week 4, 24, 28 and 36

• Change from Baseline in number of total lymphocytes in blood

  Total lymphocyte count in the blood was done at Baseline (Week 0), Week 4, Week 24, Week 28 and Week 36. All the data presented are based on results from independent assessor. Baseline was defined at Week 0. Change from Baseline is the value at indicated time points minus the Baseline value.

  Baseline (Week 0) and Week 4, 24, 28, 36

• Assessment of lymphocyte subsets in CSF (CD3+CD4+CD8+, CD19+, CD3-CD16+CD56+, CD3+CD4-CD8-)

  The count for lymphocyte subsets CD3+CD4+CD8+ "double positives" (T-lymphocyte), CD3+CD4-CD8- "double negatives" (T-lymphocyte), CD19+ (B-lymphocyte) and CD3-CD16+CD56+ (natural killer cells) in the CSF was done at Baseline (Week 0), Week 24, Week 28 and Week 36. All the data presented are based on results from independent assessor.

  Baseline (Week 0), Week 24, 28 and 36

• Change from Baseline in number of lymphocyte subsets in CSF (CD3+CD4+CD8+, CD19+, CD3-CD16+CD56+, CD3+CD4-CD8-)

  The count for lymphocyte subsets CD3+CD4+CD8+ "double positives" (T-lymphocyte), CD3+CD4-CD8- "double negatives" (T-lymphocyte), CD19+ (B-lymphocyte) and CD3-CD16+CD56+ (natural killer cells) in the CSF was done at Baseline (Week 0), Week 24, Week 28 and Week 36. All the data presented are based on results from independent assessor. Baseline was defined at Week 0. Change from Baseline is the value at indicated time points minus the Baseline value.

  Baseline (Week 0) and Week 24, 28, 36

• Assessment of lymphocyte subsets in blood (CD3+CD4+CD8+, CD19+, CD3-CD16+CD56+, CD3+CD4-CD8-)

  The count for lymphocyte subsets CD3+CD4+CD8+ "double positives" (T-lymphocyte), CD3+CD4-CD8- "double negatives" (T-lymphocyte), CD19+ (B-lymphocyte) and CD3-CD16+CD56+ (natural killer cells) in the blood was done at Baseline (Week 0), Week 4, Week 24, Week 28 and Week 36. All the data presented are based on results from independent assessor.

  Baseline (Week 0), Week 4, 24, 28 and 36

• Change from Baseline in number of lymphocyte subsets in blood (CD3+CD4+CD8+, CD19+, CD3-CD16+CD56+, CD3+CD4-CD8-)

  The count for lymphocyte subsets CD3+CD4+CD8+ "double positives" (T-lymphocyte), CD3+CD4-CD8- "double negatives" (T-lymphocyte), CD19+ (B-lymphocyte) and CD3-CD16+CD56+ (natural killer cells) in the blood was done at Baseline (Week 0), Week 4, Week 24, Week 28 and Week 36. All the data presented are based on results from independent assessor. Baseline was defined at Week 0. Change from Baseline is the value at indicated time points minus the Baseline value.

  Baseline (Week 0) and Week 4, 24, 28, 36

• Assessment of lymphocyte subset CD4 count in CSF

  The count for CD4 cells in the CSF was done at Baseline (Week 0), Week 24, Week 28 and Week 36. All data presented are based on results from the independent assessor.

  Baseline (Week 0), Week 24, 28 and 36

• Change from Baseline in lymphocyte subset CD4 count in CSF

  The count for CD4 cells in the CSF was done at Baseline (Week 0), Week 24, Week 28 and Week 36. All data presented are based on results from the independent assessor. Baseline was defined at Week 0. Change from Baseline is the value at indicated time points minus the Baseline value.

  Baseline (Week 0) and Week 24, 28, 36

• Assessment of lymphocyte subset CD4 count in blood

  The count for CD4 cells in the blood was done at Baseline (Week 0), Week 4, Week 24, Week 28 and Week 36. All data presented are based on results from the independent assessor.

  Baseline (Week 0), Week 4, 24, 28 and 36

• Change from Baseline in lymphocyte subset CD4 count in blood

  The count for CD4 cells in the blood was done at Baseline (Week 0), Week 4, Week 24, Week 28 and Week 36. All data presented are based on results from the independent assessor. Baseline was defined at Week 0. Change from Baseline is the value at indicated time points minus the Baseline value.

  Baseline (Week 0) and Week 4, 24, 28, 36

• Assessment of lymphocyte subset CD8 count in CSF

  The count for CD8 cells in the CSF was done at Baseline (Week 0), Week 24, Week 28 and Week 36. All data presented are based on results from the independent assessor.

  Baseline (Week 0), Week 24, 28 and 36

• Change from Baseline in lymphocyte subset CD8 count in CSF

  The count for CD8 cells in the CSF was done at Baseline (Week 0), Week 24, Week 28 and Week 36. All data presented are based on results from the independent assessor. Baseline was defined at Week 0. Change from Baseline is the value at indicated time points minus the Baseline value.

  Baseline (Week 0) and Week 24, 28, 36

• Assessment of lymphocyte subset CD8 count in blood

  The count for CD8 cells in the blood was done at Baseline (Week 0), Week 4, Week 24, Week 28 and Week 36. All data presented are based on results from the independent assessor.

  Baseline (Week 0), Week 4, 24, 28 and 36

• Change from Baseline in lymphocyte subset CD8 count in blood

  The count for CD8 cells in the blood was done at Baseline (Week 0), Week 4, Week 24, Week 28 and Week 36. All data presented are based on results from the independent assessor. Baseline was defined at Week 0. Change from Baseline is the value at indicated time points minus the Baseline value.

  Baseline (Week 0) and Week 4, 24, 28, 36

• Assessment of CD4:CD8 ratio in CSF

  The count for CD4:CD8 ratio in the CSF was done at Baseline (Week 0), Week 24, Week 28 and Week 36. All data presented are based on results from the independent assessor.

  Baseline (Week 0), Week 24, 28 and 36

• Change from Baseline in CD4:CD8 ratio in CSF

  The count for CD4:CD8 ratio in the CSF was done at Baseline (Week 0), Week 24, Week 28 and Week 36. All data presented are based on results from the independent assessor. Baseline was defined at Week 0. Change from Baseline is the value at indicated time points minus the Baseline value.

  Baseline (Week 0) and Week 24, 28, 36

• Assessment of CD4:CD8 ratio in blood

  The count for CD4:CD8 ratio in the blood was done at Baseline (Week 0), Week 4, Week 24, Week 28 and Week 36. All data presented are based on results from the independent assessor.

  Baseline (Week 0), Week 4, 24, 28 and 36

• Change from Baseline in CD4:CD8 ratio in blood

  The count for CD4:CD8 ratio in the blood was done at Baseline (Week 0), Week 4, Week 24, Week 28 and Week 36. All data presented are based on results from the independent assessor. Baseline was defined at Week 0. Change from Baseline is the value at indicated time points minus the Baseline value.

  Baseline (Week 0) and Week 4, 24, 28, 36

Secondary Outcomes (11)

• Assessment of CD34+ cells in the blood

  Baseline (Week 0), Week 4, 24, 28 and 36

• Change from Baseline in number of CD34+ cells in the blood

  Baseline (Week 0) and Week 4, 24, 28, 36

• Number of participants with adverse events (AEs) and Serious adverse events (SAEs)

  Up to Week 24

• Cumulative number of new gadolinium-enhancing lesions at Week 24

  Week 24

• Cumulative volume of new gadolinium-enhancing lesions at Week 24

  Week 24

Study Arms (1)

firategrast

EXPERIMENTAL

900 (females) or 1200 (males) mg twice daily for 24 weeks

Drug: firategrast

Interventions

firategrast DRUG

900 (females) or 1200 (males) mg twice daily for 24 weeks

firategrast

Eligibility Criteria

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

You may qualify if:

• Specific information regarding warnings, precautions, contraindications, adverse events (AEs), and other pertinent information on the investigational product that may impact subject eligibility is provided can be found in the SB-683699 Investigators Brochure \[GlaxoSmithKline Document Number HM2002/00094/05\].
• Subjects eligible for enrollment in the study must meet all of the following criteria:
• Written informed consent.
• Male or female, age 18 to 65.
• A diagnosis of a relapsing form of MS \[As per McDonald, 2001; Polman, 2005\], with dissemination in time and space.
• Expanded Disability Status Scale (EDSS) score of between 0 and 6.5 inclusive.
• 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.
• A minimum of two T2 lesions on brain MRI at Screening, 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. a woman who:
• has documented evidence of tubal ligation, bilateral oophorectomy or hysterectomy; or
• is 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 estradiol and Follicle Stimulating Hormone (FSH) levels consistent with menopause according to local laboratory ranges. Estrogen-containing hormone replacement therapies (HRT) are not allowed during the study.
• Of childbearing potential, has a negative urine pregnancy test at Screening and Baseline, and agrees to consistent and correct use the method of contraception listed below. Subjects will use effective contraceptive methods for at least one month prior to Screening and should continue to use the same contraceptive method throughout the study until 3 days after the last dose of firategrast.
• Progesterone-only oral contraceptives or implants (inserted at least one month prior to Screening, but not beyond the third successive year following insertion). Estrogen-containing contraceptives are not allowed during the study.
• Intrauterine Device (IUD) (inserted by a qualified clinician, with published data showing that the highest expected failure rate is less than 1% per year).

You may not qualify if:

• Subjects meeting any of the following criteria must not be enrolled in the study:
• 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 a 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 Organic Anion Transporter Protein (OATP).
• Subjects with clinically significant renal laboratory values: subjects with a calculated creatinine clearance \<60ml/min (by Cockcroft and Gault) at Screening \[Cockcroft, 1976\].
• Subjects with local urinalysis findings of 1) proteinuria, defined as ³1+ protein on urine dipstick or 2) renal tubular cell casts or 3) ³5 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 Phase.
• Presence of clinically significant hepatic laboratory values: Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT) \> 2 times the upper limit of the reference range; total bilirubin \> 1.5 the upper limit of the normal range.
• CD4 count \< 500, CD4:CD8 \< 1.0, JCV viremia in plasma or white cells, idiopathic CD4/CD8 lymphopenia or secondary lymphopenia at Screening.
• Any findings at Screening on the MRI of the brain 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).
• Uncontrolled or any active bacterial, viral, or fungal infection. 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.
• Current or history of cancer, excluding localized non-melanoma skin cancer.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (10)

GSK Investigational Site

Brussels, 1070, Belgium

Location

GSK Investigational Site

Brussels, 1200, Belgium

Location

GSK Investigational Site

Olomouc, 775 20, Czechia

Location

GSK Investigational Site

Prague, 120 00, Czechia

Location

GSK Investigational Site

Glostrup Municipality, DK-2600, Denmark

Location

GSK Investigational Site

Koebenhavn Ø, 2100, Denmark

Location

GSK Investigational Site

Lørenskog, 1478, Norway

Location

GSK Investigational Site

Gothenburg, SE-416 85, Sweden

Location

GSK Investigational Site

Stockholm, SE-171 76, Sweden

Location

GSK Investigational Site

Umeå, SE-901 85, Sweden

Location

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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2007
• First Posted: May 4, 2007
• Study Start: July 1, 2007
• Primary Completion: May 1, 2009
• Study Completion: February 1, 2010
• Last Updated: March 23, 2017

Record last verified: 2017-03

Locations

CZ (2); DK (2); SE (3); BE (2); NO (1)