Cladribine Tablets: Collaborative Study to Evaluate Impact On Central Nervous System Biomarkers in Multiple Sclerosis (CLOCK-MS)

Cladribine Tablets: Collaborative Study to Evaluate the 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).

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting
• Intervention / Treatment: Drug: Cladribine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma Medical Research Foundation
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Have a relapsing form of multiple sclerosis (RMS; to include RRMS or active secondary progressive MS)
2. Are willing and able to receive at least 2 lumbar punctures
3. Have an EDSS of 0 to ≤ 5.5 during the screening period
4. Had at least 1 relapse or 1 gadolinium-enhancing or 1 new or enlarged T2 lesion in the last 12 months
5. 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
6. Capable of giving signed informed consent

Exclusion Criteria:

1. Have any contraindication for lumbar puncture
2. Have current malignancy
3. Are infected with human immunodeficiency virus (HIV)
4. Have active chronic infections (e.g. hepatitis or tuberculosis)
5. Have signs or symptoms suggestive of progressive multifocal leukoencephalopathy (PML) in MRI
6. Have history of hypersensitivity to cladribine or any of the excipients listed in the cladribine tablets US Prescribing Information
7. Allergy or hypersensitivity to gadolinium and/or any other contraindication to perform a MRI
8. Have any other comorbid conditions that preclude participation
9. Have been previously treated with cladribine
10. Have previously been treated with ocrelizumab, alemtuzumab, rituximab, or daclizumab
11. Have received treatment with natalizumab during the last 6 months
12. Are currently receiving immunosuppressive or myelosuppressive therapy, e.g., methotrexate, cyclophosphamide, cyclosporine or azathioprine, or chronic treatment with systemic corticosteroids
13. Have received treatment with immunosuppressive or myelosuppressive therapy during the last 6 months
14. Have received chronic treatment with systemic corticosteroids during the last 4 weeks
15. Have moderate or severe hepatic impairment (Child-Pugh score >6)
16. Have moderate or severe renal impairment (creatinine clearance <60 mL per minute)
17. 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
18. Are intending to breastfeed on a cladribine tablet treatment day and/or during the 10 days after the last cladribine tablet dose.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 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	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.
Other: 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.
Other: 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.
Other: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the CSF levels of lymphocyte subtypes and markers of neuronal injury during treatment with cladribine tablets in patients with RMS	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	5 weeks, 10 weeks, 1 year, or 2 years

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: EMD Serono
• Investigators: Principal Investigator: Gregory Wu, Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2019
• Primary Completion (Actual): May 27, 2025
• Study Completion (Actual): May 27, 2025

Study Registration Dates

• First Submitted: May 23, 2019
• First Submitted That Met QC Criteria: May 23, 2019
• First Posted (Actual): May 24, 2019

Study Record Updates

• Last Update Posted (Actual): June 11, 2025
• Last Update Submitted That Met QC Criteria: June 10, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Cladribine
• Other Study ID Numbers: MS700568_0049-201906092

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• 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