Evaluation of the Safety of Sequential Rituximab and Cladribine Treatment in Patients with Relapsing-Remitting Multiple Sclerosis

The primary objective of this study is to evaluate the incidence of serious adverse events associated with the sequential administration of rituximab followed by cladribine in patients with relapsing-remitting multiple sclerosis. The assessment aims to determine if the safety profile of this sequential regimen is clinically acceptable. Secondary objectives include the evaluation of:

• The effect of sequential treatment on MRI lesions;
• The effect of sequential treatment on relapses;
• The impact on disability;
• The effect on tissue injury;
• Changes in quality of life;
• General safety markers.

The sponsor did not provide information regarding the total number of participants. The study population consists of individuals diagnosed with relapsing-remitting multiple sclerosis. Eligible participants include both males and females between the ages of 18 and 50 years. Inclusion requires a disease duration of 10 years or less and an Expanded Disability Status Scale score ranging from 0 to 5.5. Participants must demonstrate disease activity within the preceding year, evidenced by a clinical relapse, at least two T2 lesions on magnetic resonance imaging, or the presence of gadolinium enhancing lesions. Diagnosis must be confirmed according to the 2017 revised McDonald criteria.

This Phase II clinical trial is designed to evaluate the safety and efficacy of a sequential treatment regimen consisting of rituximab followed by cladribine in patients diagnosed with relapsing-remitting multiple sclerosis. The primary objective is to assess the rate of serious adverse events associated with this specific treatment sequence. Participants must meet specific inclusion criteria, including a disease duration of 10 years or less, an Expanded Disability Status Scale score between 0 and 5.5, and evidence of recent disease activity via clinical relapse or MRI findings. The study methodology involves a screening period to confirm eligibility, followed by the administration of investigational products and auxiliary medications. Secondary endpoints include the evaluation of new T2 lesions, annualized relapse rate, and changes in disability and cognitive measures. The trial is estimated to occur between 2026 and 2030.

The experimental treatment involves the sequential administration of rituximab and cladribine. Rituximab is administered via infusion at a dose of 1000 mg. Cladribine is administered as a 10 mg subcutaneous injection.

Background therapies utilized in the study include aciclovir sodium, which is administered as an 800 mg oral dose. Cetirizine dihydrochloride and pseudoephedrine hydrochloride are provided in a 10 mg oral pharmaceutical form. Methylprednisolone acetate and lidocaine hydrochloride monohydrate are administered via intravenous route at a dose of 125 mg. Sulfamethoxazole, trimethoprim, and bromhexine hydrochloride are administered as an 800 mg oral dose. Paracetamol, codeine phosphate, and buclizine hydrochloride are administered as a 1000 mg oral dose.

The primary efficacy endpoint is the occurrence of at least one treatment-related serious adverse event, defined by a relationship of possible or greater, per participant. Secondary endpoints include the proportion of patients presenting with a new MRI lesion at the end of follow-up and the mean number of new T2 lesions per patient.

Further assessments include the proportion of patients experiencing a new relapse, the proportion of patients with a steroid-treated relapse, and the annualized relapse rate during the follow-up period. Disability and cognitive function will be evaluated through the proportion of patients with confirmed disability worsening, the mean change in the Expanded Disability Status Scale, and the distribution of improved, unchanged, or worsened SDMT scores, alongside the mean change in SDMT.

Biological and patient-reported outcomes will be monitored, specifically the mean change in pNfL and pGFAp levels. Additionally, the proportion of patients showing improvement in the MSIS-29 and the mean change in MSIS-29 scores will be recorded. The proportion of patients experiencing mild or moderate adverse events with at least a probable relationship to the study medication will also be assessed.