About this trial
The purpose of the study is to evaluate the efficacy and safety of subcutaneously administered cladribine versus placebo to stop inflammation and treat disease progression of non-active secondary progressive multiple sclerosis.
Multiple sclerosis is an inflammatory disease of the central nervous system. In most patients, it starts with a relapsing course (RMS) which is caused by acute inflammatory lesions in the brain and spinal cord. RMS transforms at later stages into progressive disease (secondary progressive MS). Currently approved disease-modifying treatments are effective in reducing clinical relapses and brain and spinal lesions visible in MR, but they perform poorly in preventing disease progression and overall disability accumulation. The growing evidence shows that disease progression partially depends on chronic inflammation present in the CNS. Drugs, which may cross the blood-brain barrier and reach inflammatory cells residing in the CNS might be effective in this stage of the disease. Cladribine is one of the DMT approved for RMS. It is a synthetic purine analog with selective lymphocyte toxicity, which enter the CNS and is found in cerebrospinal fluid. In patients treated with cladribine, the oligoclonal bands tend to disappear proving that neuroinflammation is diminished.
The participants of this clinical trial with the later non-active stage of MS are enrolled to be treated with cladribine subcutaneously or a non-active comparator (placebo) for 6 months and followed for the next 2 years, with an MRI scan and clinical evaluation every 6 months. The main questions it aims to answer are if in the non-active stage of MS cladribine is potent to lessen brain volume loss and if it is potent to attenuate inflammation in the CNS.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
Lack of written informed consent
Previous cladribine treatment
Hypersensitivity to the investigational medicinal product
Eligible and willing to use interferon beta, siponimod, or mitoxantrone
Trial design
Parallel
Treatments tested in this trial
Cladribine Subcutaneous Injection
DrugCladribine subcutaneous injection, 10 mg daily, for 2-3 consecutive days (depending on individual dose)
0.9% Chloride Injection Sodium
Drug0.9% sodium chloride injected subcutaneously, 10 ml daily, for 2-3 consecutive days
Treatment groups
Trial outcomes
Primary outcomes
Percent brain volume
brain volume to total intracranial volume
Percent brain volume
brain volume to total intracranial volume
Secondary outcomes
24 weeks confirmed composite progression of disability
Time to 24-week confirmed composite progression of disability defined as the occurrence of any of the following events: (1) an increase in the EDSS score of 1 or greater in patients with baseline EDSS ≤ 5.5 or of 0.5 or greater in those with baseline EDSS \> 5.5; (2) an increase of 20% or more in Timed 25-Foot Walk; (3) an increase of 20% or more in the 9-Hole Peg Test.
Symbol-Digit Modality Test
Cognitive performance assessed with Symbol-Digit Modality Test
Symbol-Digit Modality Test
Cognitive performance assessed with Symbol-Digit Modality Test
California Verbal Learning Test
Cognitive performance assessed with California Verbal Learning Test \[Polish version 2010\]
Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Institute of Psychiatry and Neurology, Warsaw
Lead sponsor
Nalecz Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences
Collaborator
Mossakowski Medical Research Centre Polish Academy of Sciences
Collaborator
Poznan University of Medical Sciences
Collaborator
Military Institute of Aviation Medicine
Collaborator