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

Multiple Sclerosis Clinical Trial

— CLOCK-MS  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03963375
• Other study ID #: MS700568_0049-201906092
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: October 28, 2019
• Est. completion date: May 30, 2025

Study information

• Verified date: March 2024
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 47
• Est. completion date: May 30, 2025
• Est. primary completion date: May 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Sclerosis

Intervention

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.

Locations

Country	Name	City	State
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Oklahoma Medical Research Foundation	Oklahoma City	Oklahoma
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Washington University School of Medicine	EMD Serono

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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