Multiple Sclerosis, Relapsing-RemittingPhase 4CLAREMINCT05902429
Effects of Oral Cladribine on Remyelination and Inflammation in Multiple Sclerosis Patients
A Phase 4 study testing Cladribine 10 mg oral tablet in people with Multiple Sclerosis, Relapsing-Remitting, run by Pontificia Universidade Católica do Rio Grande do Sul at 1 site in Brazil.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Multiple Sclerosis, Relapsing-Remitting
- What is being tested?
- Cladribine 10 mg oral tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteBrazil
- Study dates
- 28 Apr 2021to Aug 2024
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Brazil1 site
Pontifical Catholic University of Rio Grande do Sul
Porto Alegre, Rio Grande do Sul, 9061000
About this study
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
- Being tested
- Cladribine 10 mg oral tablet
- Keywords
- multiple sclerosis, cladribine tablets, remyelination
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cladribine 10 mg oral tabletDrug
Also called Mavenclad
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.
| Study group | Role | What they receive |
|---|---|---|
| Cladribine tablets | Experimental | Not described Receives: Drug: Cladribine 10 mg oral tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of remyelinated lesions (as assessed by neuroradiologist) in q-Space myelin map
Measured: 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
Measured: 36 months after initiation of cladribine tablets treatment
Mean signal intensity of lesions in q-Space myelin map
Measured: 36 months after initiation of cladribine tablets treatment
Correlation between lymphocyte profile and remyelination parameters in q-Space myelin map
Measured: 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
Measured: 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)
Measured: 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)
Measured: Over 36 months following initiation of cladribine tablets treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2023
- Study start28 Apr 2021
- Primary completionAug 2024 (estimated)
- Study completionAug 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple Sclerosis, Relapsing-RemittingStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single-arm, open-label, phase IV, single-center, proof-of-concept clinical trial
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pontificia Universidade Católica do Rio Grande do Sul
- Sponsor type
- University, hospital or other
- Collaborators
- Merck S.A., Brazil, an affiliate of Merck KGaA, Darmstadt, Germany
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05902429
- Sponsor's protocol ID
- MS700568_0128
- Acronym
- CLAREMI
- Status last verified
- Jan 2024
- First submitted
- 5 Jun 2023
- Last updated
- 8 Jan 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Oral Cladribine on Remyelination and Inflammation in Multiple Sclerosis Patients
- ClinicalTrials.gov ID
- NCT05902429
- Acronym / sponsor ID
- CLAREMI / MS700568_0128
- Conditions
- Multiple Sclerosis, Relapsing-Remitting
- Keywords
- multiple sclerosis, cladribine tablets, remyelination
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Pontificia Universidade Católica do Rio Grande do SulUniversity, hospital or other
- Collaborators
- Merck S.A., Brazil, an affiliate of Merck KGaA, Darmstadt, Germany
- Study start
- 28 Apr 2021 (actual)
- Primary completion
- Aug 2024 (estimated)
- Study completion
- Aug 2024 (estimated)
- First posted
- 15 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single-arm, open-label, phase IV, single-center, proof-of-concept clinical trial
| Arm | Type | Receives |
|---|---|---|
| Cladribine tablets | Experimental | Drug: Cladribine 10 mg oral tablet |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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;
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cladribine 10 mg oral tabletAlso: MavencladCladribine 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. | Drug | Cladribine tablets |
Primary outcome
Proportion of remyelinated lesions (as assessed by neuroradiologist) in q-Space myelin map
Time frame: 36 months after initiation of cladribine tablets treatment
6 secondary outcomes
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
Mean signal intensity of lesions in q-Space myelin map
Time frame: 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)
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)
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
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Cladribine 10 mg oral tablet in people with Multiple Sclerosis, Relapsing-Remitting, run by Pontificia Universidade Católica do Rio Grande do Sul at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of remyelinated lesions (as assessed by neuroradiologist) in q-Space myelin map (time frame: 36 months after initiation of cladribine tablets treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2024.