Cladribine for Multiple Sclerosis

(CLOCK-MS Trial)

No longer recruiting at 5 trial locations

Overseen By Dana Perantie

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Washington University School of Medicine

Must not be taking: Immunosuppressives, Myelosuppressives, Corticosteroids

Disqualifiers: Malignancy, HIV, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how cladribine tablets affect individuals with relapsing forms of multiple sclerosis (MS), such as relapsing-remitting MS or active secondary progressive MS. Researchers will examine the impact of cladribine on specific markers in the central nervous system and blood. Participants will be divided into groups to assess these effects at different times. The trial suits individuals diagnosed with a relapsing form of MS who have experienced new or worsening symptoms in the past year and are comfortable with lumbar punctures (a procedure to collect spinal fluid). As a Phase 4 trial, this research focuses on understanding how the already FDA-approved and effective treatment benefits more patients.

Do I need to stop my current medications to join the trial?

The trial requires that you stop taking certain medications, such as immunosuppressive or myelosuppressive therapies and chronic systemic corticosteroids, before participating. If you are currently on these treatments, you may need to discontinue them to be eligible.

What is the safety track record for cladribine?

Research has shown that cladribine is generally well-tolerated by people with multiple sclerosis (MS). Studies have found that nearly 9 out of 10 patients did not experience disease progression over four years, suggesting that the treatment does not significantly worsen the condition.

Regarding safety, no current evidence indicates increased risks, such as pregnancy-related issues, for those taking cladribine. Real-world data supports its safety, as many patients have experienced fewer relapses and new MS lesions without major side effects.

The FDA has approved this treatment for use in MS, further supporting its safety. While any treatment can have side effects, cladribine has a strong record of being safe and effective for people with MS. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for multiple sclerosis, like interferons or glatiramer acetate, Cladribine offers a unique mechanism of action. It targets and reduces certain white blood cells, like lymphocytes, which are involved in the immune response that attacks the nervous system in MS. Researchers are excited about Cladribine because it can be taken orally, making it more convenient than injectable options. Additionally, its effects might last longer, potentially reducing the frequency of treatment cycles and offering sustained relief from symptoms.

What is the effectiveness track record for cladribine in treating multiple sclerosis?

Research has shown that cladribine effectively treats multiple sclerosis (MS). Studies have found that cladribine can significantly reduce relapses and the appearance of new or growing lesions on MRI scans. Over four years, nearly 90% of patients did not experience disease progression, even without new relapses. Additionally, cladribine lowered levels of a protein in the blood that is often elevated in people with MS, indicating the treatment's effectiveness. This evidence suggests that cladribine is a promising option for managing MS symptoms and slowing disease progression. Participants in this trial will be divided into groups to assess cladribine's effects at various time points, such as at the end of Week 5, Week 10, Year 1, and Year 2. ^{2 4 6 7 8}

Who Is on the Research Team?

Gregory Wu, MD, PhD

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for people with relapsing forms of multiple sclerosis who can undergo lumbar punctures, have had recent MS activity, and normal lymphocyte counts. They must be able to consent and not have any contraindications for lumbar puncture, current cancer, HIV, active chronic infections like hepatitis or tuberculosis, PML signs in MRI scans, hypersensitivity to cladribine or its components.

Inclusion Criteria

My disability level is moderate or better.

I have a type of multiple sclerosis that comes and goes.

I am willing and able to undergo at least 2 spinal taps.

Exclusion Criteria

I do not have ongoing infections like hepatitis or tuberculosis.

You are allergic to gadolinium or have a condition that prevents you from getting an MRI.

My MRI shows signs that might indicate a brain infection called PML.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cladribine tablets and undergo lumbar punctures to assess CNS biomarkers

2 years

Multiple visits including baseline, Week 5, Week 10, end of Year 1, and end of Year 2

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cladribine

Trial Overview The study tests the effects of Cladribine tablets on biomarkers in the central nervous system and blood that are relevant in relapsing forms of multiple sclerosis. It aims to understand how Cladribine works by monitoring changes in these biomarkers.

How Is the Trial Designed?

Group I: Group 4: LP at Baseline and End of Year 2 Experimental Treatment 1 Intervention

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 II: Group 3: LP at Baseline and End of Year 1 Experimental Treatment 1 Intervention

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 III: Group 2: LP at Baseline and Week 10 Experimental Treatment 1 Intervention

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 IV: Group 1: LP at Baseline and Week 5 Experimental Treatment 1 Intervention

Group 1: LP at Baseline and end of Week 5. Week 5 is the optimal time point for assessing cladribine concentrations in CSF

Cladribine is already approved in United States, European Union for the following indications:

Approved in United States as Leustatin for:

• Hairy cell leukemia
• Chronic lymphocytic leukemia (CLL)
• Non-Hodgkin's lymphoma
• Multiple sclerosis

Approved in European Union as Litak for:

• Hairy cell leukemia
• Chronic lymphocytic leukemia (CLL)
• Non-Hodgkin's lymphoma

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

EMD Serono

Industry Sponsor

Trials

147

Recruited

27,800+

Dr. Shepard

EMD Serono

Chief Medical Officer since 2021

MD from University of Cincinnati Medical School, Fellowships in Hematology and Oncology at University of Chicago Hospitals and Clinics

Miguel Fernández Alcalde

EMD Serono

Chief Executive Officer

Bachelor's Degree in Pharmacy from the University Complutense in Madrid, MBA from the University of Alcalá de Henares, Master's Degree in Management from IESE Business School

Published Research Related to This Trial

Cladribine, an antileukaemic drug, shows strong immunosuppressive activity and is being tested for its effectiveness in treating multiple sclerosis (MS).

Preliminary results from two independent randomized, placebo-controlled trials suggest that cladribine may halt the progression of chronic progressive MS, reduce relapse frequency, and improve neurological status in patients with the remitting-relapsing form of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of multiple sclerosis with cladribine (2-CDA), a new immunosuppressant agent. Theoretical basis and preliminary results]. Grieb, P., Stelmasiak, Z.[2015]

In a 96-week phase III study involving 1,326 patients with relapsing-remitting multiple sclerosis, cladribine tablets demonstrated a safety profile with a high treatment completion rate (88.6% for cladribine vs. 86.3% for placebo).

The most common adverse event was lymphopenia, which aligns with cladribine's mechanism of action, and while infections were more frequent in the cladribine group (48.3% vs. 42.5% for placebo), they were mostly mild-to-moderate, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of cladribine tablets in multiple sclerosis: the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study. Cook, S., Vermersch, P., Comi, G., et al.[2022]

Cladribine is an effective oral treatment for very active recurring multiple sclerosis, requiring only two short courses of administration over two years to maintain efficacy for up to four years, significantly reducing flare-ups and disability progression compared to placebo.

While cladribine is generally safe, it can cause lymphopenia and increase the risk of herpes zoster infections; however, long-term follow-up (up to eight years) indicates no greater risk of serious events like cancers or opportunistic infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Recommendations for the use of cladribine tablets in recurring multiple sclerosis]. Oreja-Guevara, C., García-Merino, JA., Saiz, A., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12179467/

Cladribine tablets in the new multiple sclerosis era - PMC Several recent studies have demonstrated the efficacy of CladT in reducing serum NfL (sNfL) levels over a 2-year treatment period in RRMS ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2211034825004663

The real-world efficacy of Cladribine tablets and treatment ... In conclusion, the probability of first relapse was high in this nearly nationwide cohort of Finnish subjects treated with cladribine tablets for highly active ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33975489/

Effectiveness and safety of cladribine in MS: Real-world ... Results: Among 270 patients treated with cladribine, we observed a profound reduction of both relapses and new or enlarging MRI lesions.

4. emdserono.com emdserono.com/us-en/company/news/press-releases/new-mavenclad-4-year-data-highlighting-durable-effects.html

2025-09-17 New MAVENCLAD 4-year data highlighting ... Four-year data show nearly 9 in 10 RMS patients remained free from progression independent of relapse activity (PIRA); Results highlight the ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0022510X24002053

A real-world, single Centre study considering a two-year ... Our experience provides information for the 2-years after the last dose of CLAD, confirming a higher effectiveness of CLAD when placed early in the treatment ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10106322/

Safety and efficacy of cladribine in multiple sclerosis Our analysis showed that the PFS after cladribine use is 79% (95%CI 71%, 86%). Also, 58% of patients with MS who received cladribine remained ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2211034824006837

146. Post-Approval Safety of Cladribine Tablets in the ... While data are currently scant, there is no evidence for an increased risk of adverse pregnancy outcomes in patients receiving cladribine tablets. Recommended ...

8. conferences.medicom-publishers.com conferences.medicom-publishers.com/specialisation/neurology/actrims-2025/update-on-safety-profile-of-cladribine-tablets-yields-positive-results/

Update on safety profile of cladribine tablets yields positive ... While the numbers are small, there was no evidence of an increased risk of adverse pregnancy outcomes among women receiving cladribine tablets.