Cladribine Tablets: Collaborative Study to Evaluate Impact On Central Nervous System Biomarkers in Multiple Sclerosis (CLOCK-MS)
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ClinicalTrials.gov Identifier: NCT03963375 |
Recruitment Status :
Recruiting
First Posted : May 24, 2019
Last Update Posted : January 6, 2023
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Multiple Sclerosis Multiple Sclerosis, Relapsing-Remitting | Drug: Cladribine | Phase 4 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 50 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Intervention Model Description: | All patients will receive cladribine treatment per standard of care. Patients will be randomized 1:2:2:1 to receive a total of 2 Lumbar Punctures (LP) according to 1 of the 4 following schedules: Group 1: Baseline and end of Week 5; Group 2: Baseline and end of Week 10; Group 3: Baseline and end of Year 1; Group 4: Baseline and end of Year 2 . Patients in Groups 1-3 will have the option to undergo a third LP at the end of Year 2. |
Masking: | None (Open Label) |
Primary Purpose: | Basic Science |
Official Title: | Cladribine Tablets: Collaborative Study to Evaluate the Impact On Central Nervous System Biomarkers in Multiple Sclerosis |
Actual Study Start Date : | October 28, 2019 |
Estimated Primary Completion Date : | May 30, 2025 |
Estimated Study Completion Date : | May 30, 2025 |

Arm | Intervention/treatment |
---|---|
Group 1: LP at Baseline and Week 5
Group 1: LP at Baseline and end of Week 5. Week 5 is the optimal time point for assessing cladribine concentrations in CSF
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Drug: Cladribine
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. |
Group 2: LP at Baseline and Week 10
Group 2: LP at Baseline and end of Week 10. Week 10 is the expected "nadir" time for lymphocyte and monocyte levels in CSF
|
Drug: Cladribine
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. |
Group 3: LP at Baseline and End of Year 1
Group 3: LP at Baseline and end of Year 1. To assess if cladribine effects on CSF markers are maintained at the end of the first treatment cycle
|
Drug: Cladribine
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. |
Group 4: LP at Baseline and End of Year 2
Group 4: LP at Baseline and end of Year 2. To assess if cladribine effects on CSF markers are maintained at the end of the last treatment cycle
|
Drug: Cladribine
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. |
- Changes in the CSF levels of lymphocyte subtypes and markers of neuronal injury during treatment with cladribine tablets in patients with RMS [ Time Frame: 5 weeks, 10 weeks, 1 year, or 2 years ]Change in CSF levels of CD3+ T lymphocytes, CD19+ B lymphocytes, and NfL in the CSF from baseline to second LP using quality-controlled flow cytometry and assays

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Ages Eligible for Study: | 18 Years to 65 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03963375
Contact: Gregory F Wu, MD, PhD | 314-362-3293 | gfwu@wustl.edu | |
Contact: Dana Perantie | dperantie@wustl.edu |
United States, Missouri | |
Washington University School of Medicine | Recruiting |
Saint Louis, Missouri, United States, 63110 | |
Contact: Gregory Wu, MD, PhD 314-362-3293 clockms@wustl.edu | |
Contact: Dana Perantie dperantie@wustl.edu | |
Principal Investigator: Gregory Wu, MD, PhD | |
Sub-Investigator: Anne Cross, MD | |
United States, Oklahoma | |
Oklahoma Medical Research Foundation | Recruiting |
Oklahoma City, Oklahoma, United States, 73104 | |
Contact: Gabriel Pardo, MD 405-271-6242 gabriel-pardo@omrf.org | |
United States, Pennsylvania | |
University of Pennsylvania | Recruiting |
Philadelphia, Pennsylvania, United States, 19104 | |
Contact: Amit Bar-Or, MD 215-220-9352 amitbar@upenn.edu | |
United States, Texas | |
University of Texas Southwestern Medical Center | Recruiting |
Dallas, Texas, United States, 75390 | |
Contact: Olaf Stuve, MD, PhD 214-648-4559 Olaf.Stuve@UTSouthwestern.edu | |
United States, Wisconsin | |
Medical College of Wisconsin | Recruiting |
Milwaukee, Wisconsin, United States, 53226 | |
Contact: Ahmed Obeidat, MD, PhD 414-955-0619 aobeidat@mcw.edu |
Principal Investigator: | Gregory Wu | Washington University School of Medicine |
Responsible Party: | Washington University School of Medicine |
ClinicalTrials.gov Identifier: | NCT03963375 |
Other Study ID Numbers: |
MS700568_0049-201906092 |
First Posted: | May 24, 2019 Key Record Dates |
Last Update Posted: | January 6, 2023 |
Last Verified: | January 2023 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Undecided |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Product Manufactured in and Exported from the U.S.: | No |
Multiple Sclerosis Multiple Sclerosis, Relapsing-Remitting Sclerosis Pathologic Processes Demyelinating Autoimmune Diseases, CNS Autoimmune Diseases of the Nervous System Nervous System Diseases Demyelinating Diseases |
Autoimmune Diseases Immune System Diseases Cladribine Antineoplastic Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs |