Clinical trial NCT06854094: Consolidation Therapy with Cladribine in Relapsing Multiple Sclerosis Patients
Official title: Consolidation Therapy with Immune Reconstitution Therapy (cladribine) in Relapsing Multiple Sclerosis Patients Following a Treatment with Anti-CD20 Compounds: a Pivotal Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Multiple Sclerosis
Keywords: Switch to Cladribine
Lead sponsor: Ente Ospedaliero Cantonale, Bellinzona
Sponsor class: OTHER
Collaborators: name: 3B Biotech Research
First posted: 2025-03-03
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The recruited population will consist in 70 patients with RMS treated with anti-CD20 (ocrelizumab or rituximab) for ≥12 months and/or having received 1.2/1.0 gr, respectively, of the previously mentioned drugs that are switched to cladribine because of concerns about increased risks of infections during long term anti-CD20 therapies (defined as at least 3 infectious events/year and/or a serious infection under anti-CD20 treatment and/or a documented decrease of ≥ 5% IgG compared to pre anti-CD20 therapy and/or a level of IgG below 7 gr/L (CLAD_GROUP)).

Brief summary: To investigate the impact on IgG and IgM concentration, infection risk and effectiveness of switching from anti-CD20 to cladribine compared to continued anti-CD20 treatment over 2 years in relapsing MS patients.


Eligibility criteria: Inclusion Criteria:

* Relapsing MS according to Lublin \[23\]

EDSS ≤7.0 - Male and female patients with age \>18 years - Treatment with ocrelizumab or rituximab for ≥12 months and/or having received ≥ 1.2 / 1.0 gr, respectively - For CLAD_GROUP: Planning to switch to cladribine because of concerns about increased risk of infections related to long term anti-CD20 therapies, defined as at least 3 infectious events/year or a serious infection under anti-CD20 and/or a documented decrease of ≥ 5% IgG and/or a level of IgG below 7 gr/L compared to pre- anti-CD20 therapy (will be considered as CLAD_GROUP)

- For OCR_GROUP and RTX_GROUP: continuing anti-CD20 therapies (considered as OCR_GROUP and RTX_GROUP with ocrelizumab with rituximab treatment, respectively)

- Anti-CD20 and Cladribine are prescribed according to Swiss and European SmPC.

Exclusion Criteria:

* Non-relapsing MS

Pregnancy or lactation - Contraindication to receive cladribine or to continue anti-CD20 therapies according to local label - Inability to complete an MRI - Known presence of other neurological disorders which may mimic MS including but not limited to: neuromyelitis optica, Lyme disease, untreated vitamin B12 deficiency, neurosarcoidosis and cerebrovascular disorders - Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study

- Significant or uncontrolled somatic disease or any other significant disease that may preclude patient from participating in the study

- Known active bacterial, viral, fungal, mycobacterial infection or other infection, excluding fungal infection of nail beds Infection requiring hospitalization or treatment with i.v. antibiotics within 4 weeks prior to baseline visit or oral antibiotics within 2 weeks prior to baseline visit

- History of progressive multifocal leukoencephalopathy (PML)

- Active malignancy, including solid tumors and hematological malignancies, except basal cell carcinoma, in situ squamous cell carcinoma of the skin, and in situ carcinoma of the cervix of the uterus that have been previously completely excised with documented, clear margins

- History of alcohol or drug abuse within 24 weeks prior to baseline

- Lymphocyte count \< 1000 /μL

- AST/SGOT or ALT/SGPT ≥ 3.0 Upper Limit of Normal (ULN)

Primary outcomes:
measure: changes in IgG serum concentrations 6, 12, 24 months after switching to cladribine following a treatment with anti-CD20 therapies compared to the last 12 months of antiCD20 therapy, and to patients continuing anti-CD20.
timeFrame: From enrollment to the end of treatment at 24 months
Secondary outcomes:
Other outcomes:
Locations:
city: Lugano
country: Switzerland
facility: Ospedale Regionale di Lugano, Istituto di Neuroscienze Cliniche della Svizzera Italiana, Via Tesserete 46,
state: Ticino
Study officials:
References: