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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 : October 4, 2021
Sponsor:
Collaborator:
EMD Serono
Information provided by (Responsible Party):
Washington University School of Medicine

Study Description
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Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Multiple Sclerosis Multiple Sclerosis, Relapsing-Remitting Drug: Cladribine Phase 4

Detailed Description:
This will be 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 Design
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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 : June 2023
Estimated Study Completion Date : June 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Cladribine

Arms and Interventions
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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
 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.


Outcome Measures
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Primary Outcome Measures :
  1. 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


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

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


Contacts
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Contact: Gregory F Wu, MD, PhD 314-362-3293 gfwu@wustl.edu
Contact: Dana Perantie dperantie@wustl.edu

Locations
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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         
Sponsors and Collaborators
Washington University School of Medicine
EMD Serono
Investigators
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Principal Investigator: Gregory Wu Washington University School of Medicine
More Information
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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: October 4, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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
Additional relevant MeSH terms:
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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