Effects of Oral Cladribine on Remyelination and Inflammation in Multiple Sclerosis Patients

NCT05902429 | Unknown Phase 4

• 1 other identifier: MS700568_0128
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Multiple sclerosis (MS) is a chronic, immune-mediated, demyelinating disease of the central nervous system. Typical brain lesions of the disease may be partially repaired by an endogenous remyelination process which is limited and tends to deplete over the course of the disease. Cladribine tablets are an approved treatment that promotes selective lymphocyte depletion, reducing the inflammatory activity of the disease. The present study is based on the hypothesis that improved inflammatory control through cladribine tablets provides a tissue microenvironment more favorable for remyelination of brain lesions in MS. This hypothesis will be evaluated by a single-arm, open-label, phase IV, single-center, proof-of-concept clinical trial in which 10 participants with relapsing-remitting, highly active MS, relatively early in the course of the disease, will receive conventional treatment with cladribine tablets and will be followed-up for 48 months. Neurological, neuropsychological and magnetic resonance imaging (MRI) parameters will be measured. Remyelination will be assessed by a novel MRI technique called the q-Space myelin map. Additionally, the peripheral blood lymphocyte and cytokine profiles will be evaluated in order to understand the immunological aspects that influence the remyelination capacity in patients treated with cladribine tablets. The study will be conducted in accordance with current regulations governing clinical research in Brazil.

Conditions

Multiple Sclerosis, Relapsing-Remitting

Keywords

multiple sclerosis; cladribine tablets; remyelination

Outcome Measures

Primary Outcomes (1)

• Proportion of remyelinated lesions (as assessed by neuroradiologist) in q-Space myelin map

  36 months after initiation of cladribine tablets treatment

Secondary Outcomes (6)

• Median "lesion ratio" (i.e., myelin index: lesion signal / normal appearing white matter signal) in q-Space myelin map

  36 months after initiation of cladribine tablets treatment

• Mean signal intensity of lesions in q-Space myelin map

  36 months after initiation of cladribine tablets treatment

• Correlation between lymphocyte profile and remyelination parameters in q-Space myelin map

  Transversally (at months 0, 12, 24, and 36) and longitudinally (over 36 months following initiation of cladribine tablets treatment)

• Correlation between cytokine profile and remyelination parameters in q-Space myelin map

  Transversally (at months 0, 12, 24, and 36) and longitudinally (over 36 months following initiation of cladribine tablets treatment)

• Correlation between remyelination parameters in q-Space myelin map and evolution of clinical scores (annualized relapse rate, EDSS, MSFC and their subtests)

  Over 36 months following initiation of cladribine tablets treatment

Study Arms (1)

Cladribine tablets

EXPERIMENTAL

Drug: Cladribine 10 mg oral tablet

Interventions

Cladribine 10 mg oral tablet DRUG

Cladribine tablets (Mavenclad®, Merck KGaA, Darmstadt, Germany) will be given according to the label with a cumulative dose of 3.5 mg/kg body weight distributed over 2 years as one treatment course of 1.75 mg/kg per year. Each treatment course will consist of 2 weeks of treatment, one at the beginning of the first month and one at the beginning of the second month of the respective year of treatment. Each treatment week will consist of 4 or 5 days in which the participant will receive 10 mg or 20 mg (1 or 2 tablets, respectively) as a single daily dose, depending on body weight, according to the tables available in label. Upon completion of the two treatment courses, no further courses will be required in years 3 and 4.

Also known as: Mavenclad

Cladribine tablets

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Participants who meet all of the following criteria will be included:
• Consent to participate in the study by signing the ICF;
• Age between 18 and 55 years, inclusive;
• Relapsing-remitting multiple sclerosis diagnosed according to 2017 revised McDonald's criteria;
• Highly active disease, defined as 1) occurrence of ≥2 relapses within 12 months prior to study enrolment, regardless of whether or not treatment with another disease-modifying drugs (DMD) was present; or 2) occurrence of ≥1 relapse in the previous 12 months during treatment with another DMD, together with ≥1 gadolinium-enhanced T1 lesion or ≥9 T2/FLAIR lesions on MRI performed during the same period;
• Disease duration (time since first relapse) ≤4 years;
• EDSS score ≤5.0;
• Eligibility for treatment with cladribine tablets, according to the label approved in Brazil;
• For women or men of childbearing potential: agreement to use effective contraceptive method as recommended in cladribine tablets label.

You may not qualify if:

• Participants who meet any of the following criteria will be excluded:
• Contraindications to the use of cladribine tablets (as per the label), including (but not limited to) baseline lymphopenia (\<1,000 cells/ mm³), active neoplasm or neoplasm within the last 5 years, active infections (especially tuberculosis, hepatitis B or C and HIV), latent tuberculosis without proper treatment, moderate to severe renal or hepatic impairment, use of immunosuppressants or immunosuppression for another cause;
• Pregnancy or lactation;
• Presence of other medical conditions or current or previous use of another therapy capable of interfering with neurological, neuropsychological, radiological or laboratory evaluation, as per investigator's judgment;
• Contraindications to MRI or gadolinium use;
• Inability to adhere to study procedures, as per investigator's judgment.

Sponsors & Collaborators

• Pontificia Universidade Católica do Rio Grande do Sul: lead
• Merck S.A., Brazil, an affiliate of Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (1)

Pontifical Catholic University of Rio Grande do Sul

Porto Alegre, Rio Grande do Sul, 9061000, Brazil

Location

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis

Interventions

Cladribine; Tablets

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

2-Chloroadenosine; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxyadenosines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Dosage Forms; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single-arm, open-label, phase IV, single-center, proof-of-concept clinical trial

Study Record Dates

• First Submitted: June 5, 2023
• First Posted: June 15, 2023
• Study Start: April 28, 2021
• Primary Completion: August 1, 2024
• Study Completion: August 1, 2024
• Last Updated: January 8, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)