CLADRIBINE for Multiple sclerosis

Inclusion criteria

• {"criterion_text":"- Signing the informed consent form\n- Cladribine treatment is planned and indicated and is according to label\n- 35-55 years of age at the time of signing the research informed consent form\n- RRMS diagnosis in accordance with McDonald 2017 criteria"}

Exclusion criteria

• {"criterion_text":"- Patients with other neurodegenerative disease than MS\n- Patients with claustrophobia, or a history of moderate to severe anxiety disorder or panic attacks (which could potentially lead to preterm termination of the imaging)\n- Contraindication to PET scan investigations\n- Exposure to experimental radiation in the past 12 months such that radiodosimetry limits would be exceeded by participating in this study.\n- Intolerance to previous PET scans; i.e. previous hypersensitivity reactions to any PET ligand or imaging agent or failure to participate in and comply with previous PET scans.\n- Patients with previous alemtuzumab administration\n- Patients with less than 6 months since previous administration of ocrelizumab or rituximab (or with abnormal B-cell counts)\n- Patients with less than 1 month since previous administration of other DMT\n- Abnormal lymphocyte counts\n- Patients with human immunodeficiency virus (HIV).\n- Patients with active chronic infection (tuberculosis or hepatitis).\n- Patients with active malignancy.\n- Patients with moderate or severe renal impairment (creatinine clearance <60 mL/min)\n- Patients that are pregnant or breast-feeding\n- Corticosteroid treatment within 4 weeks of imaging\n- Patients with significant abnormal findings other than MS in the screening MRI."}

Primary endpoints

• {"endpoint_text":"- Change in microglial cell activation in different brain areas (NAWM normal appearing grey matter and the chronic active/ smoldering (slowly expanding) lesions) before and after 18 months of treatment with cladribine evaluated with [11C]PK11195-PET-imaging.","definition_or_measurement_approach":"Measured by [11C]PK11195-PET-imaging comparing baseline and after 18 months of treatment in specified brain areas (NAWM, NAGM, chronic active/smoldering lesions)."}

Secondary endpoints

• {"endpoint_text":"- Change in microglial cell activation in different brain areas (normal appearing white matter (NAWM), normal appearing grey matter (NAGM) and the chronic active/ smoldering lesions) before and after 18 months of treatment with cladribine evaluated with QSM-MRI.","definition_or_measurement_approach":"Measured by QSM-MRI comparing baseline and after 18 months in NAWM, NAGM and chronic active/smoldering lesions."}
• {"endpoint_text":"- Change in the total lesion load of the white matter MS plaques at different time points using MRI","definition_or_measurement_approach":"Assessed using MRI measurements of total white matter lesion load at multiple time points."}
• {"endpoint_text":"- Change in total brain, white matter (WM) and gray matter (GM) volumes using MRI at different time points of the study","definition_or_measurement_approach":"Measured by MRI volumetric analysis at specified time points."}
• {"endpoint_text":"- Change in MD (mean diffusivity) and FA (fractional anisotropy) using DTI (diffusion tensor imaging at different time points of the study","definition_or_measurement_approach":"Measured by DTI to determine MD and FA at multiple time points."}
• {"endpoint_text":"- Correlation of the baseline microglial activation status to the clinical outcome parameters at the end of the study (18 months) to evaluate whether high microglial activation is predictive of higher likelihood of progression and other measures of disability.","definition_or_measurement_approach":"Correlation analysis between baseline microglial activation measures and clinical outcome parameters at 18 months."}
• {"endpoint_text":"- Correlation of the baseline microglial activation status to the MRI parameters","definition_or_measurement_approach":"Correlation analysis between baseline microglial activation and MRI parameter changes."}
• {"endpoint_text":"- Different microglial activation at baseline in the study group when compared to microglial activation in a group of age-matched previously imaged healthy controls","definition_or_measurement_approach":"Comparison of baseline microglial activation between study participants and age-matched previously imaged healthy controls."}
• {"endpoint_text":"- Different microglial activation in the study group to microglial activation in an independent group of previously imaged age-matched untreated MS-patients.","definition_or_measurement_approach":"Comparison of baseline microglial activation between study participants and an independent group of previously imaged age-matched untreated MS patients."}

Finland

Earliest CTIS Part Ii Submission Date

13-12-2024

Latest Decision Or Authorization Date

19-12-2024

Processing Time Days

6

Number Of Sites

1

Number Of Participants

15

Primary sponsor

Full Name

Varsinais-Suomen hyvinvointialue

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Finland