Multiple SclerosisNCT04640818
Safety and Efficacy of Cladribine Therapy After Anti CD20 Therapy
An observational study of Multiple Sclerosis, run by Claudio Gobbi at 1 site in Switzerland.
Trial summary
Prolonged anti CD20 therapy for the treatment of active multiple sclerosis leading to continuous B cell depletion is associated with hypogammaglobulinemia predisposing to a potentially increased risk of serious infections, particularly in the more disabled and aged patients. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Cladribine Oral Tablet, Rituximab and Ocrelizumab
- Type of treatment
- Pill or oral medicine
- How many people
- 45 participants
- Where
- 1 siteSwitzerland
- Study dates
- 17 Dec 2020to 31 Oct 2022
- Phase
- Observational
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with relapsing multiple sclerosis
Who may be able to join
- Relapsing MS according to Lublin;
- Treatment with ocrelizumab or rituximab for ≥18 months and having received 1.8 / 3.0 gr, respectively;
- CLAD_GROUP: Planning to switch to cladribine because of concerns about increased risks of infections related to hypogammaglobulinemia developing during long term anti CD20 therapies or a documented decrease of ≥10% IgG and/or IgM compared to pre- anti CD20 therapy;
- or CD20_GROUP: no need to stop CD20 therapy due decrease of ≥10% IgG and/or IgM, or increased risk of infections related to hypogammaglobulinemia or other reasons, continued anti CD20 therapies clinically indicated;
- EDSS ≤7.0;
- Age >18 years.
Who cannot join
- Non relapsing MS;
- Pregnancy - breastfeeding;
- Contraindications to perform MRI;
- Contraindication to receive cladribine or to continue anti CD therapies
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
Neurocenter of Southern Switzerland, Ospedale Regionale di Lugano
Lugano, Canton Ticino, 6903
About this study
Official title: Safety and Efficacy of a Therapy With Cladribine Following a Treatment With Anti CD20 Compounds in Relapsing Multiple Sclerosis Patients: a Pilot Study
Prolonged anti CD20 therapy for the treatment of active multiple sclerosis leading to continuous B cell depletion is associated with hypogammaglobulinemia predisposing to a potentially increased risk of serious infections, particularly in the more disabled and aged patients. No data have been published on the sequential use of anti CD20 therapies and cladribine, that is thought to act as an immune reconstitution agent. his study aims at investigating IgG and IgM serum concentration changes at 6 and 12 months after switching to cladribine in patients previously treated with anti CD20 therapies (ie, ocrelizumab ≥1.8 gr or rituximab 3.0 gr) for ≥18 months, as compared to continued anti CD20 therapies.
Read the detailed description
The study population will include patients with remitting relapsing multiple sclerosis consulting the Multiple Sclerosis Center of Neurocenter of Southern Switzerland.
Enrolled patients will have 5 Study Visits, one every 3 months according to clinical practice. At visits at 3 and 6 months only adverse events will be collected for study purposes. Clinical assessments will be performed at baseline, Month 6 and Month 12. Clinical assessments correspond to medical exams performed routinely in MS patients treated with anti CD20 or cladribine therapy: clinical assessments, monitoring haemoglobin parameters, serum immunoglobulins, liver and renal function.(6, 12 months), radiological disability progression and biomarker of ongoing neurodegeneration (12 months).
- Conditions
- Multiple Sclerosis
- Being tested
- Cladribine Oral Tablet, Rituximab, Ocrelizumab
- Keywords
- anti CD20 therapy, cladribine
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cladribine Oral TabletDrug
Also called Mavenclade
Treatment according to the label and medical prescription
RituximabDrug
Also called Mabthera, Rixathon
Treatment according to the label and medical prescription
OcrelizumabDrug
Also called Ocrevus
Treatment according to the label and medical prescription
| Study group | Role | What they receive |
|---|---|---|
| CLAD-GROUP | Patients with cladribine therapy Receives: Drug: Cladribine Oral Tablet | |
| CD20-GROUP | Patients with anti CD20 therapy (ocrelizumab or rituximab) Receives: Drug: Rituximab; Drug: Ocrelizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in IgG serum concentrations in Cald-Group
Standard laboratory test
Measured: 6 months
Changes in IgM serum concentrations in Cald-Group
Standard laboratory test
Measured: 6 months
Changes in IgG serum concentrations in Clad-Group
Standard laboratory test
Measured: 12 months
Changes in IgM serum concentrations in Clad-Group
Standard laboratory test
Measured: 12 months
Secondary outcomes (11)
Changes in IgG serum concentrations after switching to cladribine, as compared to continued anti CD20 therapies
Standard laboratory test
Measured: 6 months
Changes in IgM serum concentrations after switching to cladribine, as compared to continued anti CD20 therapies
Standard laboratory test
Measured: 6 months
Changes in IgG serum concentrations after switching to cladribine, as compared to continued anti CD20 therapies
Standard laboratory test
Measured: 12 months
Changes in IgM serum concentrations after switching to cladribine, as compared to continued anti CD20 therapies
Standard laboratory test
Measured: 12 months
Proportion of patients reaching NEDA -3
NEDA -3: no relapses, no disability progression, no new/enlarging or Gd enhancing brain or spinal MR lesions
Measured: 12 months
Annualized relapse rate (ARR) over 12 months after switching to cladribine as compared to patients continuing anti CD20 therapies
ARR will be calculated based on recorded number of relapses
Measured: 12 months
Proportion of patients with disability progression
Expanded disability scale 0-6 (6 worst outcome)
Measured: 6 months
Proportion of patients with disability progression
Expanded disability scale 0-6 (6 worst outcome)
Measured: 12 months
Number/volume of cumulative new T2/ enlarging lesions at brain and spinal MRI over 12 months after switching to cladribine, as compared to patients continuing anti CD20 therapies
Evaluation of MRI
Measured: 12 months
Number/volume of cumulative Gd enhancing lesions at brain and spinal MRI over 12 months after switching to cladribine, as compared to patients continuing anti CD20 therapies
Evaluation of MRI
Measured: 12 months
Changes in serum neurofilament light chain concentration
single-molecule array (Simoa) assay
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2020
- Study start17 Dec 2020
- Primary completion31 Oct 2022 (estimated)
- Study completion31 Oct 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple SclerosisStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Claudio Gobbi
- Sponsor type
- Other government
- Collaborators
- Merck AG Switzerland
- Responsible party
- Sponsor-investigator, Claudio Gobbi, Ospedale Civico, Lugano
- Investigators
- Claudio Gobbi, MD, Principal investigator, Ospedale Regionale di Lugano, Neurocentro della Svizzera italiana, Centro Sclerosi multipla
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04640818
- Sponsor's protocol ID
- EOCNSIMS.2001
- Status last verified
- Mar 2022
- First submitted
- 18 Nov 2020
- Last updated
- 23 Mar 2022
- 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 23 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of a Therapy With Cladribine Following a Treatment With Anti CD20 Compounds in Relapsing Multiple Sclerosis Patients: a Pilot Study
- ClinicalTrials.gov ID
- NCT04640818
- Acronym / sponsor ID
- EOCNSIMS.2001
- Conditions
- Multiple Sclerosis
- Keywords
- anti CD20 therapy, cladribine
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- Claudio GobbiOther government
- Collaborators
- Merck AG Switzerland
- Study start
- 17 Dec 2020 (actual)
- Primary completion
- 31 Oct 2022 (estimated)
- Study completion
- 31 Oct 2022 (estimated)
- First posted
- 23 Nov 2020 (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.
Prolonged anti CD20 therapy for the treatment of active multiple sclerosis leading to continuous B cell depletion is associated with hypogammaglobulinemia predisposing to a potentially increased risk of serious infections, particularly in the more disabled and aged patients. No data have been published on the sequential use of anti CD20 therapies and cladribine, that is thought to act as an immune reconstitution agent. his study aims at investigating IgG and IgM serum concentration changes at 6 and 12 months after switching to cladribine in patients previously treated with anti CD20 therapies (ie, ocrelizumab ≥1.8 gr or rituximab 3.0 gr) for ≥18 months, as compared to continued anti CD20 therapies.
Detailed description
The study population will include patients with remitting relapsing multiple sclerosis consulting the Multiple Sclerosis Center of Neurocenter of Southern Switzerland.
Enrolled patients will have 5 Study Visits, one every 3 months according to clinical practice. At visits at 3 and 6 months only adverse events will be collected for study purposes. Clinical assessments will be performed at baseline, Month 6 and Month 12. Clinical assessments correspond to medical exams performed routinely in MS patients treated with anti CD20 or cladribine therapy: clinical assessments, monitoring haemoglobin parameters, serum immunoglobulins, liver and renal function.(6, 12 months), radiological disability progression and biomarker of ongoing neurodegeneration (12 months).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CLAD-GROUP | – | Drug: Cladribine Oral TabletPatients with cladribine therapy |
| CD20-GROUP | – | Drug: Rituximab, Drug: OcrelizumabPatients with anti CD20 therapy (ocrelizumab or rituximab) |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with relapsing multiple sclerosis
Key inclusion criteria (6 listed)
- Relapsing MS according to Lublin;
- Treatment with ocrelizumab or rituximab for ≥18 months and having received 1.8 / 3.0 gr, respectively;
- CLAD_GROUP: Planning to switch to cladribine because of concerns about increased risks of infections related to hypogammaglobulinemia developing during long term anti CD20 therapies or a documented decrease of ≥10% IgG and/or IgM compared to pre- anti CD20 therapy;
- or CD20_GROUP: no need to stop CD20 therapy due decrease of ≥10% IgG and/or IgM, or increased risk of infections related to hypogammaglobulinemia or other reasons, continued anti CD20 therapies clinically indicated;
- EDSS ≤7.0;
Key exclusion criteria (4 listed)
- Non relapsing MS;
- Pregnancy - breastfeeding;
- Contraindications to perform MRI;
- Contraindication to receive cladribine or to continue anti CD therapies
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 Oral TabletAlso: MavencladeTreatment according to the label and medical prescription | Drug | CLAD-GROUP |
| RituximabAlso: Mabthera, RixathonTreatment according to the label and medical prescription | Drug | CD20-GROUP |
| OcrelizumabAlso: OcrevusTreatment according to the label and medical prescription | Drug | CD20-GROUP |
Primary outcome
Changes in IgG serum concentrations in Cald-Group
Time frame: 6 months
Standard laboratory test
Changes in IgM serum concentrations in Cald-Group
Time frame: 6 months
Standard laboratory test
Changes in IgG serum concentrations in Clad-Group
Time frame: 12 months
Standard laboratory test
Changes in IgM serum concentrations in Clad-Group
Time frame: 12 months
Standard laboratory test
11 secondary outcomes
Changes in IgG serum concentrations after switching to cladribine, as compared to continued anti CD20 therapies
Time frame: 6 months
Changes in IgM serum concentrations after switching to cladribine, as compared to continued anti CD20 therapies
Time frame: 6 months
Changes in IgG serum concentrations after switching to cladribine, as compared to continued anti CD20 therapies
Time frame: 12 months
Changes in IgM serum concentrations after switching to cladribine, as compared to continued anti CD20 therapies
Time frame: 12 months
Proportion of patients reaching NEDA -3
Time frame: 12 months
Annualized relapse rate (ARR) over 12 months after switching to cladribine as compared to patients continuing anti CD20 therapies
Time frame: 12 months
Proportion of patients with disability progression
Time frame: 6 months
Proportion of patients with disability progression
Time frame: 12 months
Number/volume of cumulative new T2/ enlarging lesions at brain and spinal MRI over 12 months after switching to cladribine, as compared to patients continuing anti CD20 therapies
Time frame: 12 months
Number/volume of cumulative Gd enhancing lesions at brain and spinal MRI over 12 months after switching to cladribine, as compared to patients continuing anti CD20 therapies
Time frame: 12 months
Changes in serum neurofilament light chain concentration
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2022.
- 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.
Claudio Gobbi, MD principal investigator
Ospedale Regionale di Lugano, Neurocentro della Svizzera italiana, Centro Sclerosi multipla
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Multiple Sclerosis, run by Claudio Gobbi at 1 site in Switzerland.
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 6 inclusion and 4 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 23 Mar 2022. 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 Switzerland. 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.
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?
Changes in IgG serum concentrations in Cald-Group (time frame: 6 months). The study lists 4 primary outcomes in all. 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 23 Mar 2022.