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

NCT ID: NCT03963375

Last Updated: 2025-06-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 47 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-28
• Study Completion Date: 2025-05-27

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).

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.

Conditions

Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

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

Group Type: OTHER

Cladribine

Intervention Type: 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.

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

Group Type: OTHER

Cladribine

Intervention Type: 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.

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

Group Type: OTHER

Cladribine

Intervention Type: 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.

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

Group Type: OTHER

Cladribine

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

EMD Serono

INDUSTRY

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gregory Wu

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Oklahoma Medical Research Foundation

Oklahoma City, Oklahoma, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

Other Identifiers

MS700568_0049-201906092

Identifier Type: -

Identifier Source: org_study_id