Multiple SclerosisPhase 2NCT00469378
Study Of White Blood Cells In The Cerebrospinal Fluid And Blood Of Patients With Relapsing Forms Of Multiple Sclerosis
A Phase 2 study testing firategrast in people with Multiple Sclerosis, run by GlaxoSmithKline at 10 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- firategrast
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 10 sitesin 5 countries
- Study dates
- Jul 2007to Feb 2010
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 18Show fewer
- 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.
- OR
- 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).
- 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.
Who cannot join
- 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).
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- 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.
- Any abnormality on 12-lead Electrocardiogram (ECG) at Screening which is clinically significant in the opinion of the investigator.
- 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. Alcohol abuse is defined as an average weekly intake of greater than 21 units for men and 14 units for women or an average daily intake of greater than three units for men and two units for women. One unit is equivalent to approximately 250mL of beer or one measure of spirits or one glass of wine.
- Use of an investigational drug for a condition other than MS within 30 days or 5 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 laboratory tests) that may affect the interpretation of clinical efficacy or safety data or prevent the subject from safely completing the assessments required by the protocol.
- Contraindications, in the opinion of the investigator, to lumbar puncture, e.g. congenital or acquired spine or CNS conditions that may render LPs unsafe, platelet count of less than 50 GI/L and/or an International Normalized Ratio (INR) of greater than or equal to 1.5 (by history), known history of clotting/bleeding disorder, needle phobia.
Trial locations and contacts
10 sites in 5 countries.
10 sites in 5 countries
Sweden3 sites
GSK Investigational Site
Gothenburg, SE-416 85
GSK Investigational Site
Stockholm, SE-171 76
GSK Investigational Site
Umeå, SE-901 85
Belgium2 sites
GSK Investigational Site
Brussels, 1070
GSK Investigational Site
Brussels, 1200
Czechia2 sites
GSK Investigational Site
Olomouc, 775 20
GSK Investigational Site
Prague, 120 00
Denmark2 sites
GSK Investigational Site
Glostrup Municipality, DK-2600
GSK Investigational Site
Koebenhavn Ø, 2100
About this study
Official title: An Open-label Study of Leukocyte Counts in the Cerebrospinal Fluid and Blood of Subjects With Relapsing Forms of Multiple Sclerosis Following Treatment With Firategrast
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
- Being tested
- firategrast
- Keywords
- firategrast, lymphocytes, leukocytes, SB-683699, cerebrospinal fluid, relapsing forms of multiple sclerosis
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
firategrastDrug
900 (females) or 1200 (males) mg twice daily for 24 weeks
| Study group | Role | What they receive |
|---|---|---|
| firategrast | Experimental | 900 (females) or 1200 (males) mg twice daily for 24 weeks Receives: Drug: firategrast |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline (Week 0) and Week 4, 24, 28, 36
Secondary outcomes (11)
Assessment of CD34+ cells in the blood
Blood sample was examined to test the mobilization of CD34+ early hematopoietic progenitor cells from the bone marrow at Baseline (Week 0), Week 4, Week 24, Week 28 and Week 36. CD34+ was measured using two different approaches by the independent assessor: a. Without a CD45 side scatter histogram (SSH) added and this analysis was conducted by the individual flow cytometry laboratories and the independent assessor and b. With a CD45 SSH added and the analysis was conducted by the independent assessor only. All the data presented are based on results from independent assessor.
Measured: Baseline (Week 0), Week 4, 24, 28 and 36
Change from Baseline in number of CD34+ cells in the blood
Blood sample was examined to test the mobilization of CD34+ early hematopoietic progenitor cells from the bone marrow at Baseline (Week 0), Week 4, Week 24, Week 28 and Week 36. CD34+ was measured using two different approaches by the independent assessor: a. Without a CD45 SSH added and this analysis was conducted by the individual flow cytometry laboratories and the independent assessor and b. With a CD45 SSH added and the analysis was conducted by the independent assessor only. 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.
Measured: Baseline (Week 0) and Week 4, 24, 28, 36
Number of participants with adverse events (AEs) and Serious adverse events (SAEs)
AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE was any untoward medical occurrence that, at any dose results in death, was life threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect or was considered as medically significant. On-treatment AEs and SAEs have been presented.
Measured: Up to Week 24
Cumulative number of new gadolinium-enhancing lesions at Week 24
The number of new gadolinium-enhancing lesions was determined by magnetic resonance imaging (MRI) scan. The cumulative number of new gadolinium-enhancing lesions at 24 weeks of treatment was derived as the sum of new gadolinium-enhancing lesions counted at all visits from Week 4 up to Week 24. In the event that a participant had missing MRI data for a gadolinium enhanced lesion parameter during the on-treatment period (scans at Weeks 4-24 inclusive), the missing value was imputed using the mean value for that parameter for all non-missing scans during the treatment period.
Measured: Week 24
Cumulative volume of new gadolinium-enhancing lesions at Week 24
The volume of new gadolinium-enhancing lesions was determined by MRI scan. The cumulative volume of new gadolinium-enhancing lesions was calculated at each visit from Week 4 up to Week 24. In the event that a participant had missing MRI data for a gadolinium enhanced lesion parameter during the on-treatment period (scans at Weeks 4-24 inclusive), the missing value was imputed using the mean value for that parameter for all non-missing scans during the treatment period.
Measured: Week 24
Cumulative number of persistent gadolinium-enhancing lesions at Week 24
The number of persistent gadolinium-enhancing lesions was determined by MRI scan. The cumulative number of persistent gadolinium-enhancing lesions at 24 weeks of treatment was derived as the sum of persistent gadolinium-enhancing lesions counted at all visits from Week 4 up to Week 24. In the event that a participant had missing MRI data for a gadolinium enhanced lesion parameter during the on-treatment period (scans at Weeks 4-24 inclusive), the missing value was imputed using the mean value for that parameter for all non-missing scans during the treatment period.
Measured: Week 24
Cumulative total number of enhancing Lesions at Week 24
The total number of gadolinium-enhancing lesions was determined by MRI scan. The cumulative total number gadolinium-enhancing lesions at 24 weeks of treatment was derived as the sum of the new and persistent gadolinium-enhancing lesions counted at all visits from Week 4 up to Week 24. In the event that a participant had missing MRI data for a gadolinium enhanced lesion parameter during the on-treatment period (scans at Weeks 4-24 inclusive), the missing value was imputed using the mean value for that parameter for all non-missing scans during the treatment period.
Measured: Week 24
Plasma and CSF levels of firategrast
Pharmacokinetic sampling for plasma and CSF levels of firategrast was done on Week 24 of treatment period and Week 28 and 36 of core follow up period, however the results for these parameters were not analyzed.
Measured: Week 24, 28 and 36
The relationship between plasma concentration of firategrast and lymphocyte count in the CSF
Sampling to determine concentration of firategrast and lymphocyte count in the CSF was supposed to be done on Week 24 of treatment phase and Week 28 and 36 of core follow up period to investigate any relationship between lymphocyte counts and systemic exposure to firategrast and its metabolite GW786375X. There was no quantifiable concentrations of firategast or its metabolite GW786375X, hence, the results were not analyzed.
Measured: Week 24, 28 and 36
The relationship between plasma concentration of firategrast and lymphocyte count in the blood
Sampling to determine concentration of firategrast and lymphocyte count in the blood was supposed to be done on Week 24 of treatment phase and Week 28 and 36 of core follow up period to investigate any relationship between lymphocyte counts and systemic exposure to firategrast and its metabolite GW786375X, however, the results were not analyzed.
Measured: Week 24, 28 and 36
The relationship between the presence of the A allele of rs887829 and bilirubin levels
Participants were assessed for the presence of A allele of rs887829 which is associated with Gilbert's syndrome. Gilbert's syndrome is benign and characterized by transient increases in bilirubin levels (>1.5XUpper limit of normal [ULN]). Participants who were carrying two copies of A allele of rs887829, suggested that elevations in bilirubin (maximum total bilirubin [MTB] >1.5xULN, >1.0 to 1.5xULN and less than or equal to 1.0xULN) were due to benign Gilbert's syndrome. Genotypes AA, AG and GG were analyzed.
Measured: Baseline (Week 0)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2007 (estimated)
- Study startJul 2007
- Primary completionMay 2009
- Study completionFeb 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00469378
- Sponsor's protocol ID
- A4M108119
- Status last verified
- Mar 2017
- First submitted
- 2 May 2007
- Last updated
- 23 Mar 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Study of Leukocyte Counts in the Cerebrospinal Fluid and Blood of Subjects With Relapsing Forms of Multiple Sclerosis Following Treatment With Firategrast
- ClinicalTrials.gov ID
- NCT00469378
- Acronym / sponsor ID
- A4M108119
- Conditions
- Multiple Sclerosis
- Keywords
- firategrast, lymphocytes, leukocytes, SB-683699, cerebrospinal fluid, relapsing forms of multiple sclerosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- Jul 2007
- Primary completion
- May 2009 (actual)
- Study completion
- Feb 2010 (actual)
- First posted
- 4 May 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| firategrast | Experimental | Drug: firategrast900 (females) or 1200 (males) mg twice daily for 24 weeks |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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].
- 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.
Key exclusion criteria (22 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| firategrast900 (females) or 1200 (males) mg twice daily for 24 weeks | Drug | firategrast |
Primary outcome
Assessment of total leukocytes in cerebrospinal fluid (CSF)
Time frame: Baseline (Week 0), Week 24, 28 and 36
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.
Change from Baseline in number of total leukocytes in CSF
Time frame: Baseline (Week 0) and Week 24, 28 and 36
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.
Assessment of total leukocytes in blood
Time frame: Baseline (Week 0), Week 4, 24, 28 and 36
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.
Change from Baseline in number of total leukocytes in blood
Time frame: Baseline (Week 0) and Week 4, 24, 28, 36
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.
Assessment of total lymphocytes in CSF
Time frame: Baseline (Week 0), Week 24, 28 and 36
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.
Change from Baseline in number of total lymphocytes in CSF
Time frame: Baseline (Week 0) and Week 24, 28, 36
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.
Assessment of total lymphocytes in blood
Time frame: Baseline (Week 0), Week 4, 24, 28 and 36
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.
Change from Baseline in number of total lymphocytes in blood
Time frame: Baseline (Week 0) and Week 4, 24, 28, 36
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.
Assessment of lymphocyte subsets in CSF (CD3+CD4+CD8+, CD19+, CD3-CD16+CD56+, CD3+CD4-CD8-)
Time frame: Baseline (Week 0), Week 24, 28 and 36
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.
Change from Baseline in number of lymphocyte subsets in CSF (CD3+CD4+CD8+, CD19+, CD3-CD16+CD56+, CD3+CD4-CD8-)
Time frame: Baseline (Week 0) and Week 24, 28, 36
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.
Assessment of lymphocyte subsets in blood (CD3+CD4+CD8+, CD19+, CD3-CD16+CD56+, CD3+CD4-CD8-)
Time frame: Baseline (Week 0), Week 4, 24, 28 and 36
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.
Change from Baseline in number of lymphocyte subsets in blood (CD3+CD4+CD8+, CD19+, CD3-CD16+CD56+, CD3+CD4-CD8-)
Time frame: Baseline (Week 0) and Week 4, 24, 28, 36
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.
Assessment of lymphocyte subset CD4 count in CSF
Time frame: Baseline (Week 0), Week 24, 28 and 36
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.
Change from Baseline in lymphocyte subset CD4 count in CSF
Time frame: Baseline (Week 0) and Week 24, 28, 36
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.
Assessment of lymphocyte subset CD4 count in blood
Time frame: Baseline (Week 0), Week 4, 24, 28 and 36
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.
Change from Baseline in lymphocyte subset CD4 count in blood
Time frame: Baseline (Week 0) and Week 4, 24, 28, 36
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.
Assessment of lymphocyte subset CD8 count in CSF
Time frame: Baseline (Week 0), Week 24, 28 and 36
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.
Change from Baseline in lymphocyte subset CD8 count in CSF
Time frame: Baseline (Week 0) and Week 24, 28, 36
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.
Assessment of lymphocyte subset CD8 count in blood
Time frame: Baseline (Week 0), Week 4, 24, 28 and 36
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.
Change from Baseline in lymphocyte subset CD8 count in blood
Time frame: Baseline (Week 0) and Week 4, 24, 28, 36
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.
Assessment of CD4:CD8 ratio in CSF
Time frame: Baseline (Week 0), Week 24, 28 and 36
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.
Change from Baseline in CD4:CD8 ratio in CSF
Time frame: Baseline (Week 0) and Week 24, 28, 36
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.
Assessment of CD4:CD8 ratio in blood
Time frame: Baseline (Week 0), Week 4, 24, 28 and 36
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.
Change from Baseline in CD4:CD8 ratio in blood
Time frame: Baseline (Week 0) and Week 4, 24, 28, 36
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.
11 secondary outcomes
Assessment of CD34+ cells in the blood
Time frame: Baseline (Week 0), Week 4, 24, 28 and 36
Change from Baseline in number of CD34+ cells in the blood
Time frame: Baseline (Week 0) and Week 4, 24, 28, 36
Number of participants with adverse events (AEs) and Serious adverse events (SAEs)
Time frame: Up to Week 24
Cumulative number of new gadolinium-enhancing lesions at Week 24
Time frame: Week 24
Cumulative volume of new gadolinium-enhancing lesions at Week 24
Time frame: Week 24
Cumulative number of persistent gadolinium-enhancing lesions at Week 24
Time frame: Week 24
Cumulative total number of enhancing Lesions at Week 24
Time frame: Week 24
Plasma and CSF levels of firategrast
Time frame: Week 24, 28 and 36
The relationship between plasma concentration of firategrast and lymphocyte count in the CSF
Time frame: Week 24, 28 and 36
The relationship between plasma concentration of firategrast and lymphocyte count in the blood
Time frame: Week 24, 28 and 36
The relationship between the presence of the A allele of rs887829 and bilirubin levels
Time frame: Baseline (Week 0)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
10 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing firategrast in people with Multiple Sclerosis, run by GlaxoSmithKline at 10 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Sweden, Belgium, Czechia, Denmark, Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of total leukocytes in cerebrospinal fluid (CSF) (time frame: Baseline (Week 0), Week 24, 28 and 36). The study lists 24 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Mar 2017.