Safety and Efficacy of Cladribine Therapy After Anti CD20 Therapy

Multiple Sclerosis Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04640818
• Other study ID #: EOCNSIMS.2001
• Status: Active, not recruiting
• Start date: December 17, 2020
• Est. completion date: October 31, 2022

Study information

• Verified date: March 2022
• Source: Ospedale Civico, Lugano
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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. 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.

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 45
• Est. completion date: October 31, 2022
• Est. primary completion date: October 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• Non relapsing MS;

• Pregnancy - breastfeeding;

• Contraindications to perform MRI;

• Contraindication to receive cladribine or to continue anti CD therapies

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• Cladribine Oral Tablet
Treatment according to the label and medical prescription
• Rituximab
Treatment according to the label and medical prescription
• Ocrelizumab
Treatment according to the label and medical prescription

Locations

Country	Name	City	State
Switzerland	Neurocenter of Southern Switzerland, Ospedale Regionale di Lugano	Lugano	Ticino

Sponsors (2)

Lead Sponsor	Collaborator
Claudio Gobbi	Merck AG Switzerland

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Frequency of infections	Safety endpoint	6 months
Other	Frequency of infections	Safety endpoint	12 months
Other	Intensity of infections	Safety endpoint, intensity will be rated according to the following definitions: Mild: Awareness of a sign or symptom that does not interfere with the study participant's usual activity or is transient, resolved without treatment and with no sequelae; Moderate: Interferes with the study participant's usual activity and/or requires symptomatic treatment; Severe: Symptom(s) causing severe discomfort and significant impact of the study participant's usual activity and requires treatment.; Serious: results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/ incapacity, is a congenital anomaly/ birth defect, or is otherwise considered as medically important.	6 months
Other	Intensity of infections	Safety endpoint, intensity will be rated according to the following definitions: Mild: Awareness of a sign or symptom that does not interfere with the study participant's usual activity or is transient, resolved without treatment and with no sequelae; Moderate: Interferes with the study participant's usual activity and/or requires symptomatic treatment; Severe: Symptom(s) causing severe discomfort and significant impact of the study participant's usual activity and requires treatment.; Serious: results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/ incapacity, is a congenital anomaly/ birth defect, or is otherwise considered as medically important.	12 months
Other	Proportion of patients with abnormal creatinine values of clinical relevance	Safety endpoint	6 months
Other	Proportion of patients with abnormal creatinine values of clinical relevance	Safety endpoint	12 months
Other	Proportion of patients with abnormal ASAT values of clinical relevance	Safety endpoint	6 months
Other	Proportion of patients with abnormal ASAT values of clinical relevance	Safety endpoint	12 months
Other	Proportion of patients with abnormal ALAT values of clinical relevance	Safety endpoint	6 months
Other	Proportion of patients with abnormal ALAT values of clinical relevance	Safety endpoint	12 months
Other	Proportion of patients with any abnormal hematology values of clinical relevance	Safety endpoint	6 months
Other	Proportion of patients with any abnormal hematology values of clinical relevance	Safety endpoint	12 months
Primary	Changes in IgG serum concentrations in Cald-Group	Standard laboratory test	6 months
Primary	Changes in IgM serum concentrations in Cald-Group	Standard laboratory test	6 months
Primary	Changes in IgG serum concentrations in Clad-Group	Standard laboratory test	12 months
Primary	Changes in IgM serum concentrations in Clad-Group	Standard laboratory test	12 months
Secondary	Changes in IgG serum concentrations after switching to cladribine, as compared to continued anti CD20 therapies	Standard laboratory test	6 months
Secondary	Changes in IgM serum concentrations after switching to cladribine, as compared to continued anti CD20 therapies	Standard laboratory test	6 months
Secondary	Changes in IgG serum concentrations after switching to cladribine, as compared to continued anti CD20 therapies	Standard laboratory test	12 months
Secondary	Changes in IgM serum concentrations after switching to cladribine, as compared to continued anti CD20 therapies	Standard laboratory test	12 months
Secondary	Proportion of patients reaching NEDA -3	NEDA -3: no relapses, no disability progression, no new/enlarging or Gd enhancing brain or spinal MR lesions	12 months
Secondary	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	12 months
Secondary	Proportion of patients with disability progression	Expanded disability scale 0-6 (6 worst outcome)	6 months
Secondary	Proportion of patients with disability progression	Expanded disability scale 0-6 (6 worst outcome)	12 months
Secondary	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	12 months
Secondary	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	12 months
Secondary	Changes in serum neurofilament light chain concentration	single-molecule array (Simoa) assay	12 months