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

NCT03963375 | Completed Phase 4 DMC FDA Drug

• 1 other identifier: MS700568_0049-201906092
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 5

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).

Conditions

Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (4)

Group 1: LP at Baseline and Week 5

OTHER

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

Group 2: LP at Baseline and Week 10

OTHER

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

Group 3: LP at Baseline and End of Year 1

OTHER

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

Group 4: LP at Baseline and End of Year 2

OTHER

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

Interventions

Cladribine 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 1: LP at Baseline and Week 5; Group 2: LP at Baseline and Week 10; Group 3: LP at Baseline and End of Year 1; Group 4: LP at Baseline and End of Year 2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Washington University School of Medicine: lead
• EMD Serono: collaborator

Study Sites (5)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Oklahoma Medical Research Foundation

Oklahoma City, Oklahoma, 73104, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting

Interventions

Cladribine

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

2-Chloroadenosine; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxyadenosines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Gregory Wu

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 23, 2019
• First Posted: May 24, 2019
• Study Start: October 28, 2019
• Primary Completion: May 27, 2025
• Study Completion: May 27, 2025
• Last Updated: June 11, 2025

Record last verified: 2025-06

Locations

US (5)