Cladribine vs Placebo for Non-active Progressive Multiple Sclerosis (CLASP-MS).

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