Cladribine for Multiple Sclerosis

(CLOCK-MS Trial)

Recruiting at 4 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

47 Participants Needed

Trial Summary

What is the purpose of this trial?

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).

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 data supports the effectiveness of the drug Cladribine for treating multiple sclerosis?

Research shows that Cladribine, a drug used for certain blood cancers, may help stop the progression of multiple sclerosis and reduce relapses. Preliminary results from trials are promising, indicating it can improve neurological health in patients with relapsing forms of the disease. ^{1 2 3 4 5}

Is Cladribine safe for humans?

Cladribine has been approved for treating multiple sclerosis, and studies have been conducted to assess its safety. However, real-world data on its safety is still limited, indicating that more research is needed to fully understand its safety profile. ^{2 3 6 7 8}

How is the drug Cladribine different from other treatments for multiple sclerosis?

Cladribine is unique because it is an oral medication that acts as a selective immune reconstitution therapy, targeting the immune system to reduce disease activity in very active forms of multiple sclerosis. Unlike some other treatments, it is a prodrug (a medication that is converted into an active form inside the body) and was initially used for blood cancers before being adapted for MS treatment. ^{1 2 3 4 9}

Research Team

Gregory Wu, MD, PhD

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

References

1. Poland pubmed.ncbi.nlm.nih.gov

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

2. Spain pubmed.ncbi.nlm.nih.gov

[Recommendations for the use of cladribine tablets in recurring multiple sclerosis]. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Safety and tolerability of cladribine tablets in multiple sclerosis: the CLARITY (CLAdRIbine Tablets treating multiple sclerosis orallY) study. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Cladribine treatment for highly active multiple sclerosis: Real-world clinical outcomes for years 3 and 4. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Treatment With Cladribine Selects IFNγ+IL17+ T Cells in RRMS Patients - An In Vitro Study. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

A prospective observational longitudinal study with a two-year follow-up of multiple sclerosis patients on Cladribine. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of cladribine in MS: Real-world experience from two tertiary centres. [2022]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Predictors of Cladribine Effectiveness and Safety in Multiple Sclerosis: A Real-World, Multicenter, 2-Year Follow-Up Study. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Chronic cladribine administration increases amyloid beta peptide generation and plaque burden in mice. [2021]