Cladribine treatment for non-active progressive multiple sclerosis

Safety and Efficacy of Subcutaneous Cladribine for Nonrelapsing, Secondary Progressive Multiple Sclerosis (CLASP-MS): a Randomized, Placebo-controlled, Double-blind, Phase 2 Study.

This study is testing whether a new treatment called cladribine can help people with non-active progressive multiple sclerosis feel better and slow down their disease.

Quick facts

• Phase: PHASE2; PHASE3
• Study type: Interventional
• Enrollment: 188 (estimated)
• Ages: 30 Years to 65 Years
• Sex: All
• Sponsor: Institute of Psychiatry and Neurology, Warsaw (other)
• Drugs / interventions: natalizumab, ocrelizumab, alemtuzumab, methotrexate
• Locations: 1 site (Warsaw, Masovian Voivodeship)
• Trial ID: NCT05961644 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the efficacy and safety of subcutaneously administered cladribine compared to a placebo in patients with non-active secondary progressive multiple sclerosis. It is a randomized, placebo-controlled, double-blind study involving 188 participants, who will receive either cladribine or placebo over a treatment period followed by a 96-week follow-up. The study aims to assess the impact of cladribine on disease progression and inflammation in the central nervous system, with a focus on neuroimaging outcomes. Participants will be monitored for safety and efficacy through multiple assessments during the follow-up period.

Who should consider this trial

Good fit: Ideal candidates are adults aged 30-65 with a diagnosis of secondary progressive multiple sclerosis who have not experienced relapses in the past year.

Not a fit: Patients with active relapsing forms of multiple sclerosis or those with a shorter disease duration may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly slow disease progression and improve quality of life for patients with secondary progressive multiple sclerosis.

How similar studies have performed: Other studies have shown promise with similar approaches, but this specific application of cladribine in non-active progressive MS is relatively novel.

Eligibility criteria

Inclusion Criteria:

* Written informed consent
* Diagnosis of relapse-onset, secondary progressive multiple sclerosis based on the 2017 McDonald criteria
* Progression of disability over 24 months defined as an increase in the EDSS score of 1 or more for patients with EDSS ≤ 5.5 or of 0.5 or more for patients with EDSS \> 5.5
* Lack of relapses over last 12 months
* EDSS of 3.5 - 7.5 inclusive
* Age of 30 - 65 years inclusive
* Duration of MS of 10 years or longer
* Pre-menopausal women must refrain from heterosexual intercourse or use a contraception method with a failure rate of \< 1% from enrolment up to 6 months after the last dose of the investigational medicinal product
* Men must refrain from heterosexual intercourse from enrolment up to 6 months after the last dose of the investigational medicinal product or use a barrier method of contraception, with their female partners using a contraception method with a failure rate of \<1%
* Able to fulfill all protocol requirements as judged by the investigator

Exclusion Criteria:

* Lack of written informed consent
* Previous cladribine treatment
* Hypersensitivity to the investigational medicinal product
* Eligible and willing to use interferon beta, siponimod, or mitoxantrone
* Unable to undergo magnetic resonance imaging
* Pregnancy or breastfeeding
* Does not agree to use contraception methods defined above
* Diseases of the nervous system, such as tumors, stroke, traumatic injury, encephalomyelitis, B12 deficiency, or demyelinating diseases other than multiple sclerosis
* Major comorbidities, such as cancer, liver failure, kidney failure, heart failure (NYHA II-III), or any other disease that may jeopardize patient safety or make it impossible for the patient to fulfill protocol requirements
* Relapse within last 12 months
* Chronic treatment with corticosteroids or immunosuppressants (eg, azathioprine, methotrexate, cyclosporine) within last 6 months
* Disease-modifying treatments for multiple sclerosis (no washout is required for interferons beta, glatiramer acetate, and dimethyl fumarate; washout of \> 6 months for teriflunomide, fingolimod, and natalizumab \[an accelerate elimination procedure may be used for teriflunomide instead\]; washout of \> 12 months for ocrelizumab, mitoxantrone, and alemtuzumab)
* Relapsing-remitting multiple sclerosis
* Primary progressive multiple sclerosis
* Hepatitis B or hepatitis C, including detectable HbsA, anti-HBc, or anti-HCV antibodies in serum
* HIV infection, including a positive screening test (anti-HIV 1/2, protein 24)
* Active or latent tuberculosis, including a positive result of the QuantiFERON TB Gold test during screening or within 3 months (an inconclusive test must be repeated; two inconclusive tests are taken as a positive result)
* Other infection that may be worsened by treatment with cladribine
* Lymphopenia (\< 1000/μl), neutrocytopenia (\< 1500/μl), or thrombocytopenia
* Alanine aminotransferase or aspartate aminotransferase \> 2 x ULN (can be repeated when 1.5-3x ULN); Total bilirubin \> 1.5 x ULN (can be repeated when 1.5-3 x ULN); Hemoglobin \> 9.5 g/dL (can be repeated when 9-9.4 g/dL)
* Lack of vaccination against COVID-19 - the time from the last dose of a full vaccination regimen is shorter than 6 weeks
* Any vaccination within last 6 weeks
* Lack of cancer screening or suspicion of cancer or necessity to carry out additional studies after the following examinations done at screening: chest X-ray in all participants; mammography or breast ultrasound in women; cervical smear in women; prostate-specific antigen in men
* Patient does not have detectable antibodies against Varicella zoster virus in serum or a proof of two-dose vaccination against this virus (last dose at least 6 months before enrolment)
* Use of oral or parenteral anticoagulants or antiplatelets other than acetylsalicylic acid

Where this trial is running

Warsaw, Masovian Voivodeship

• Institute of Psychiatry and Neurology — Warsaw, Masovian Voivodeship, Poland (RECRUITING)

Study contacts

• Principal investigator: Iwona Kurkowska-Jastrzebska, MD, PhD — Institute for Psychiatry and Neurology
• Study coordinator: Iwona Kurkowska-Jastrzebska, MD, PhD

Conditions: Multiple Sclerosis, Secondary Progressive, Multiple Sclerosis, Cladribine, Multiple Sclerosis Secondary Progressive, Brain Volume, Quantitative Susceptibility Mapping, Magnetic Resonance Imaging, Cognitive assessment