Skip to main content
OpenTrials
Completed

NCT Number: NCT03963375

Cladribine Tablets: Collaborative Study to Evaluate Impact On Central Nervous System Biomarkers in Multiple Sclerosis

The purpose of this study is to better understand the mechanism of action (MoA) of cladribine tablets by exploring the effect on central nervous system (CNS) and blood biomarkers relevant in the relapsing forms of multiple sclerosis (RMS; to include relapsing-remitting MS [RRMS] or active secondary progressive MS).

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Multiple Sclerosis Autoimmune Diseases Autoimmune Diseases of the Nervous System Demyelinating Autoimmune Diseases, CNS Demyelinating Diseases Immune System Diseases Multiple Sclerosis, Relapsing-Remitting Nervous System Diseases

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Washington University School of Medicine, St Louis, Missouri, United States

Loading trial locations.

About this study

This is an open label, randomized, multicenter collaborative research Phase 4 biomarker study, designed to generate hypotheses to better understand the MoA of cladribine tablets in RMS (to include RRMS or active secondary progressive MS). The study is designed to generate hypotheses regarding the impact and relevance of cladribine tablet activity in the CNS by assessing the cerebrospinal (CSF) levels of lymphocyte subsets, other immune cells, neuronal injury markers and soluble immunological markers in study participants with RMS before and during treatment with cladribine tablets, and the association of these CSF markers with corresponding blood markers and with clinical outcomes.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Have a relapsing form of multiple sclerosis (RMS; to include RRMS or active secondary progressive MS)
  • Are willing and able to receive at least 2 lumbar punctures
  • Have an EDSS of 0 to ≤ 5.5 during the screening period
  • Had at least 1 relapse or 1 gadolinium-enhancing or 1 new or enlarged T2 lesion in the last 12 months
  • Have absolute lymphocyte count (ALC) within normal range of the local laboratory or assessed as normal by the investigator within the 3 week screening period and meet all other eligibility criteria for cladribine tablet treatment
  • Capable of giving signed informed consent

Exclusion criteria

  • Have any contraindication for lumbar puncture
  • Have current malignancy
  • Are infected with human immunodeficiency virus (HIV)
  • Have active chronic infections (e.g. hepatitis or tuberculosis)
  • Have signs or symptoms suggestive of progressive multifocal leukoencephalopathy (PML) in MRI
  • Have history of hypersensitivity to cladribine or any of the excipients listed in the cladribine tablets US Prescribing Information
  • Allergy or hypersensitivity to gadolinium and/or any other contraindication to perform a MRI
  • Have any other comorbid conditions that preclude participation
  • Have been previously treated with cladribine
  • Have previously been treated with ocrelizumab, alemtuzumab, rituximab, or daclizumab
  • Have received treatment with natalizumab during the last 6 months
  • Are currently receiving immunosuppressive or myelosuppressive therapy, e.g., methotrexate, cyclophosphamide, cyclosporine or azathioprine, or chronic treatment with systemic corticosteroids
  • Have received treatment with immunosuppressive or myelosuppressive therapy during the last 6 months
  • Have received chronic treatment with systemic corticosteroids during the last 4 weeks
  • Have moderate or severe hepatic impairment (Child-Pugh score >6)
  • Have moderate or severe renal impairment (creatinine clearance <60 mL per minute)
  • Are pregnant or unwilling or unable to use effective contraception during cladribine tablets dosing and for 6 months after the last dose in each treatment course
  • Are intending to breastfeed on a cladribine tablet treatment day and/or during the 10 days after the last cladribine tablet dose.

Treatment and study plan

cladribine

Drug

All participants will receive cladribine 10 mg tablets at a cumulative dosage of 3.5 mg/kg divided into 2 treatment courses as per the United States Prescribing Information (USPI) (1.75 mg/kg per treatment course; Year 1 and Year 2 treatment). Patients will be randomized 1:2:2:1 to receive a total of 2 Lumbar Punctures at specific time points during the treatment cycle.

Primary outcomes

  1. Change in CD3+ T Cells % From Baseline to Week 5

    Time frame: Baseline to Week 5 (5 weeks after first cladribine dose)

    Change in CSF level of CD3+ T lymphocytes from Baseline to second LP at Week 5, using quality-controlled flow cytometry and assays. Within-group differences from baseline to Week 5 were analyzed using the Wilcoxon signed-rank test because outcome differences were non-normally distributed. Positive number indicates increase in CD3+ T cell percentage and a negative number indicates decrease in CD3+ T cell percentage.

  2. Change in CD3+ T Cells % From Baseline to Week 10

    Time frame: Baseline to Week 10 (10 weeks after first cladribine dose)

    Change in CSF level of CD3+ T lymphocytes from Baseline to second LP at Week 10, using quality-controlled flow cytometry and assays. Within-group differences from Baseline to Week 10 were analyzed using the Wilcoxon signed-rank test because outcome differences were non-normally distributed. Positive number indicates increase in CD3+ T cell percentage and a negative number indicates decrease in CD3+ T cell percentage.

  3. Change in CD3+ T Cells % From Baseline to Year 1

    Time frame: Baseline to Year 1 (45 weeks after first cladribine dose)

    Change in CSF level of CD3+ T lymphocytes from Baseline to second LP at Year 1, using quality-controlled flow cytometry and assays. Within-group differences from Baseline to Year 1 were analyzed using the Wilcoxon signed-rank test because outcome differences were non-normally distributed. Positive number indicates increase in CD3+ T cell percentage and a negative number indicates decrease in CD3+ T cell percentage.

  4. Change in CD3+ T Cells % From Baseline to Year 2

    Time frame: Baseline to Year 2 (45 weeks after last cladribine dose)

    Change in CSF level of CD3+ T lymphocytes from Baseline to second LP at Year 2, using quality-controlled flow cytometry and assays. Within-group differences from Baseline to Year 2 were analyzed using the Wilcoxon signed-rank test because outcome differences were non-normally distributed. Positive number indicates increase in CD3+ T cell percentage and a negative number indicates decrease in CD3+ T cell percentage.

  5. Change in CD3+ T Cells Absolute Numbers (Cells/mL) From Baseline to Week 5

    Time frame: Baseline to Week 5

    Change in CSF level of CD3+ T cells absolute numbers from Baseline to second LP at Week 5, using quality-controlled flow cytometry and assays. Within-group differences from baseline to Week 5 were analyzed using the Wilcoxon signed-rank test because outcome differences were non-normally distributed. Positive number indicates increase in CD3+ T cells absolute numbers and a negative number indicates decrease in CD3+ T cells absolute numbers.

  6. Change in CD3+ T Cells Absolute Numbers (Cells/mL) From Baseline to Week 10

    Time frame: Baseline to Week 10 (10 weeks after first cladribine dose)

    Change in CSF level of CD3+ T cells absolute numbers from Baseline to second LP at Week 10, using quality-controlled flow cytometry and assays. Within-group differences from Baseline to Week 10 were analyzed using the Wilcoxon signed-rank test because outcome differences were non-normally distributed. Positive number indicates increase in CD3+ T cells absolute numbers and a negative number indicates decrease in CD3+ T cells absolute numbers.

  7. Change in CD3+ T Cells Absolute Numbers (Cells/mL) From Baseline to Year 1

    Time frame: Baseline to Year 1 (45 weeks after first cladribine dose)

    Change in CSF level of CD3+ T cells absolute numbers from Baseline to second LP at Year 1, using quality-controlled flow cytometry and assays. Within-group differences from Baseline to Year 1 were analyzed using the Wilcoxon signed-rank test because outcome differences were non-normally distributed. Positive number indicates increase in CD3+ T cells absolute numbers and a negative number indicates decrease in CD3+ T cells absolute numbers.

  8. Change in CD3+ T Cells Absolute Numbers (Cells/mL) From Baseline to Year 2

    Time frame: Baseline to Year 2 (45 weeks after last cladribine dose)

    Change in CSF level of CD3+ T cells absolute numbers from Baseline to second LP at Year 2, using quality-controlled flow cytometry and assays. Within-group differences from Baseline to Year 2 were analyzed using the Wilcoxon signed-rank test because outcome differences were non-normally distributed. Positive number indicates increase in CD3+ T cells absolute numbers and a negative number indicates decrease in CD3+ T cells absolute numbers.

  9. Change in CD19+ B Cells % From Baseline to Week 5

    Time frame: Baseline to Week 5 (5 weeks after first cladribine dose)

    Change in CSF level of CD19+ B lymphocytes from Baseline to second LP at Week 5, using quality-controlled flow cytometry and assays. Within-group differences from Baseline to Week 5 were analyzed using the Wilcoxon signed-rank test because outcome differences were non-normally distributed. Positive number indicates increase in CD19+ B cell percentage and a negative number indicates decrease in CD19+ B cell percentage.

  10. Change in CD19+ B Cells % From Baseline to Week 10

    Time frame: Baseline to Week 10 (10 weeks after first cladribine dose)

    Change in CSF level of CD19+ B lymphocytes from Baseline to second LP at Week 10, using quality-controlled flow cytometry and assays. Within-group differences from Baseline to Week 10 were analyzed using the Wilcoxon signed-rank test because outcome differences were non-normally distributed. Positive number indicates increase in CD19+ B cell percentage and a negative number indicates decrease in CD19+ B cell percentage.

  11. Change in CD19+ B Cells % From Baseline to Year 1

    Time frame: Baseline to Year 1 (45 weeks after first cladribine dose)

    Change in CSF level of CD19+ B lymphocytes from Baseline to second LP at Year 1, using quality-controlled flow cytometry and assays. Within-group differences from Baseline to Year 1 were analyzed using the Wilcoxon signed-rank test because outcome differences were non-normally distributed. Positive number indicates increase in CD19+ B cell percentage and a negative number indicates decrease in CD19+ B cell percentage.

  12. Change in CD19+ B Cells % From Baseline to Year 2

    Time frame: Baseline to Year 2 (45 weeks after last cladribine dose)

    Change in CSF level of CD19+ B lymphocytes from Baseline to second LP at Year 2, using quality-controlled flow cytometry and assays. Within-group differences from Baseline to Year 2 were analyzed using the Wilcoxon signed-rank test because outcome differences were non-normally distributed. Positive number indicates increase in CD19+ B cell percentage and a negative number indicates decrease in CD19+ B cell percentage.

  13. Change in CD19+ B Cells Absolute Numbers (Cells/mL) From Baseline to Week 5

    Time frame: Baseline to Week 5 (5 weeks after first cladribine dose)

    Change in CSF level of CD19+ B cells absolute numbers from Baseline to second LP at Week 5, using quality-controlled flow cytometry and assays. Within-group differences from Baseline to Week 5 were analyzed using the Wilcoxon signed-rank test because outcome differences were non-normally distributed. Positive number indicates increase in CD19+ B cells absolute numbers and a negative number indicates decrease in CD19+ B cells absolute numbers.

  14. Change in CD19+ B Cells Absolute Numbers (Cells/mL) From Baseline to Week 10

    Time frame: Baseline to Week 10 (10 weeks after first cladribine dose)

    Change in CSF level of CD19+ B cells absolute numbers from Baseline to second LP at Week 10, using quality-controlled flow cytometry and assays. Within-group differences from Baseline to Week 10 were analyzed using the Wilcoxon signed-rank test because outcome differences were non-normally distributed. Positive number indicates increase in CD19+ B cells absolute numbers and a negative number indicates decrease in CD19+ B cells absolute numbers.

  15. Change in CD19+ B Cells Absolute Numbers (Cells/mL) From Baseline to Year 1

    Time frame: Baseline to Year 1 (45 weeks after first cladribine dose)

    Change in CSF level of CD19+ B cells absolute numbers from Baseline to second LP at Year 1, using quality-controlled flow cytometry and assays. Within-group differences from Baseline to Year 1 were analyzed using the Wilcoxon signed-rank test because outcome differences were non-normally distributed. Positive number indicates increase in CD19+ B cells absolute numbers and a negative number indicates decrease in CD19+ B cells absolute numbers.

  16. Change in CD19+ B Cells Absolute Numbers (Cells/mL) From Baseline to Year 2

    Time frame: Baseline to Year 2 (45 weeks after last cladribine dose)

    Change in CSF level of CD19+ B cells absolute numbers from Baseline to second LP at Year 2, using quality-controlled flow cytometry and assays. Within-group differences from Baseline to Year 2 were analyzed using the Wilcoxon signed-rank test because outcome differences were non-normally distributed. Positive number indicates increase in CD19+ B cells absolute numbers and a negative number indicates decrease in CD19+ B cells absolute numbers.

  17. Change in the Neurofilament Light Chain (NfL) Level From Baseline to Week 5

    Time frame: Baseline to Week 5 (5 weeks after first cladribine dose)

    Change in CSF level NfL (measured in pg/mL) from baseline to week 5 using the highly sensitive Neurology 4-Plex D Advantage Plus (N4PD+) single molecule array (SIMOA) technology. A single batch of samples with duplicates were run at the conclusion of the study. Within-group differences from baseline to Week 5 were analyzed using the Wilcoxon signed-rank test because outcome differences were non-normally distributed. Positive number indicates increase in NfL value and a negative number indicates decrease in NfL value.

  18. Change in the Neurofilament Light Chain (NfL) Level From Baseline to Week 10

    Time frame: Baseline to Week 10 (10 weeks after first cladribine dose)

    Change in CSF level NfL (measured in pg/mL) from baseline to Week 10 using the highly sensitive Neurology 4-Plex D Advantage Plus (N4PD+) single molecule array (SIMOA) technology. A single batch of samples with duplicates were run at the conclusion of the study. Within-group differences from baseline to Week 10 were analyzed using the Wilcoxon signed-rank test because outcome differences were non-normally distributed. Positive number indicates increase in NfL value and a negative number indicates decrease in NfL value.

  19. Change in the Neurofilament Light Chain (NfL) Level From Baseline to Year 1

    Time frame: Baseline to Year 1 (45 weeks after first cladribine dose)

    Change in CSF level NfL (measured in pg/mL) from baseline to Year 1 using the highly sensitive Neurology 4-Plex D Advantage Plus (N4PD+) single molecule array (SIMOA) technology. A single batch of samples with duplicates were run at the conclusion of the study. Within-group differences from baseline to Year 1 were analyzed using the Wilcoxon signed-rank test because outcome differences were non-normally distributed. Positive number indicates increase in NfL value and a negative number indicates decrease in NfL value.

  20. Change in the Neurofilament Light Chain (NfL) Level From Baseline to Year 2

    Time frame: Baseline to Year 2 (45 weeks after last cladribine dose)

    Change in CSF level NfL (measured in pg/mL) from baseline to year 2 using the highly sensitive Neurology 4-Plex D Advantage Plus (N4PD+) single molecule array (SIMOA) technology. A single batch of samples with duplicates were run at the conclusion of the study. Within-group differences from baseline to year 2 were analyzed using the Wilcoxon signed-rank test because outcome differences were non-normally distributed. Positive number indicates increase in NfL value and a negative number indicates decrease in NfL value.

Sponsors and collaborators

Lead sponsor

Gregory Wu

Other

Collaborators

  • EMD Serono

Registry information

Official study title

Cladribine Tablets: Collaborative Study to Evaluate the Impact On Central Nervous System Biomarkers in Multiple Sclerosis

Acronym: CLOCK-MS

Important dates

Study start
2019
Primary completion
2025
Study completion
2025
First posted
May 24, 2019
Registry last updated
Jul 28, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.