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

January 5, 2024 updated by: Pontificia Universidade Católica do Rio Grande do Sul
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
10

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
    • RS
      • Porto Alegre, RS, Brazil, 9061000
        • Pontifical Catholic University of Rio Grande do Sul

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion criteria:

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.

Exclusion criteria:

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Cladribine tablets
Drug: Cladribine 10 mg oral tablet
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.
Other Names:
  • Mavenclad

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Proportion of remyelinated lesions (as assessed by neuroradiologist) in q-Space myelin map
Time Frame: 36 months after initiation of cladribine tablets treatment
36 months after initiation of cladribine tablets treatment

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Median "lesion ratio" (i.e., myelin index: lesion signal / normal appearing white matter signal) in q-Space myelin map
Time Frame: 36 months after initiation of cladribine tablets treatment
36 months after initiation of cladribine tablets treatment
Mean signal intensity of lesions in q-Space myelin map
Time Frame: 36 months after initiation of cladribine tablets treatment
36 months after initiation of cladribine tablets treatment
Correlation between lymphocyte profile and remyelination parameters in q-Space myelin map
Time Frame: Transversally (at months 0, 12, 24, and 36) and longitudinally (over 36 months following initiation of cladribine tablets treatment)
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
Time Frame: Transversally (at months 0, 12, 24, and 36) and longitudinally (over 36 months following initiation of cladribine tablets treatment)
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)
Time Frame: Over 36 months following initiation of cladribine tablets treatment
Over 36 months following initiation of cladribine tablets treatment
Correlation between remyelination parameters in q-Space myelin map and evolution of neuropsychological scores (BICAMS and MFIS subtests)
Time Frame: Over 36 months following initiation of cladribine tablets treatment
Over 36 months following initiation of cladribine tablets treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Pontificia Universidade Católica do Rio Grande do Sul

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Merck S.A., Brazil, an affiliate of Merck KGaA, Darmstadt, Germany

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 28, 2021

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2024

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 5, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 5, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 15, 2023

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 8, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 5, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MS700568_0128

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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