Study Of White Blood Cells In The Cerebrospinal Fluid And Blood Of Patients With Relapsing Forms Of Multiple Sclerosis
- Registration Number
- NCT00469378
- Lead Sponsor
- GlaxoSmithKline
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 46
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description firategrast firategrast 900 (females) or 1200 (males) mg twice daily for 24 weeks
- Primary Outcome Measures
Name Time Method Assessment of total leukocytes in blood 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.
Assessment of total leukocytes in cerebrospinal fluid (CSF) 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 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.
Change from Baseline in lymphocyte subset CD4 count in CSF 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.
Change from Baseline in lymphocyte subset CD4 count in blood 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 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.
Assessment of lymphocyte subset CD8 count in blood 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 CD4:CD8 ratio in CSF 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.
Change from Baseline in number of total leukocytes in blood 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 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.
Assessment of total lymphocytes in blood 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 lymphocyte subsets in blood (CD3+CD4+CD8+, CD19+, CD3-CD16+CD56+, CD3+CD4-CD8-) 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.
Change from Baseline in lymphocyte subset CD8 count in CSF 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.
Change from Baseline in number of total lymphocytes in CSF 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.
Change from Baseline in number of total lymphocytes in blood 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-) 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-) 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-) 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.
Assessment of lymphocyte subset CD4 count in CSF 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.
Assessment of lymphocyte subset CD4 count in blood 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 CD8 count in blood 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 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.
Assessment of CD4:CD8 ratio in blood 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 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.
- Secondary Outcome Measures
Name Time Method Cumulative total number of enhancing Lesions at Week 24 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.
Cumulative number of persistent gadolinium-enhancing lesions at Week 24 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.
Number of participants with adverse events (AEs) and Serious adverse events (SAEs) Up to Week 24 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.
Assessment of CD34+ cells in the blood Baseline (Week 0), Week 4, 24, 28 and 36 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.
Change from Baseline in number of CD34+ cells in the blood Baseline (Week 0) and Week 4, 24, 28, 36 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.
Cumulative number of new gadolinium-enhancing lesions at Week 24 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.
Cumulative volume of new gadolinium-enhancing lesions at Week 24 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.
Plasma and CSF levels of firategrast Week 24, 28 and 36 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.
The relationship between plasma concentration of firategrast and lymphocyte count in the CSF Week 24, 28 and 36 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.
The relationship between the presence of the A allele of rs887829 and bilirubin levels Baseline (Week 0) 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.
The relationship between plasma concentration of firategrast and lymphocyte count in the blood Week 24, 28 and 36 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.
Trial Locations
- Locations (1)
GSK Investigational Site
🇸🇪Umeå, Sweden