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

Trial statusRecruiting
Trial phasePhase 2, Phase 3
Trial typeInterventional
Biological sexAll
Age30-65
SponsorInstitute of Psychiatry and Neurology, Warsaw

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 volunteers

Qualifiers

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

Design model

Parallel

Treatments tested in this trial

  • Cladribine Subcutaneous Injection

    Drug

    Cladribine subcutaneous injection, 10 mg daily, for 2-3 consecutive days (depending on individual dose)

  • 0.9% Chloride Injection Sodium

    Drug

    0.9% sodium chloride injected subcutaneously, 10 ml daily, for 2-3 consecutive days

Treatment groups

188 Participants
are divided into 2 treatment groups
Group A: ExperimentalExperimental treatment 1 intervention
Group B: ControlPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

1

Percent brain volume

brain volume to total intracranial volume

Time frame
26 week following baseline
2

Percent brain volume

brain volume to total intracranial volume

Time frame
122 week following baseline

Secondary outcomes

1

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.

Time frame
96 week
2

Symbol-Digit Modality Test

Cognitive performance assessed with Symbol-Digit Modality Test

Time frame
26 week
3

Symbol-Digit Modality Test

Cognitive performance assessed with Symbol-Digit Modality Test

Time frame
96 week
4

California Verbal Learning Test

Cognitive performance assessed with California Verbal Learning Test \[Polish version 2010\]

Time frame
26 week

Other outcomes

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