MESENCHYMAL STROMAL CELLS, EX VIVO CULTURED for Multiple sclerosis | Primary progressive multiple sclerosis | Secondary progressive multiple sclerosis

Inclusion criteria

• {"criterion_text":"- Age ≥18 to ≤55, both genders\n- Diagnosis of secondary progressive or primary progressive MS using revised McDonald criteria of clinically definite MS\n- An EDSS score of 4 to 7\n- Disease duration 2 - 18 years\n- Signed, written informed consent"}

Exclusion criteria

• {"criterion_text":"- Treatment with cytotoxic medications during the last 3 months prior to inclusion\n- History of malignancy, other than basal cell carcinoma of the skin or carcinoma in situ that has been in remission for more than one year within the last 10 years\n- Severely limited life expectancy by another co-morbid illness\n- History of previous diagnosis of myelodysplasia or previous hematologic disease (including lymphoproliferative disease, bone marrow insufficiency or previous lymphoid irradiation) or current clinically relevant abnormalities of white blood cell counts\n- Immunocompromised patients\n- Estimated glomerular filtration rate <60 ml/min/1.73 m2 or known renal failure\n- Bleeding or clotting diathesis or the use of antithrombotic or anticoagulative treatment\n- Platelet (thrombocyte) count <100 x 10*9/L\n- Participation in another experimental clinical study with administration of another IMP within the preceding 12 months\n- Contraindications to MRI\n- Prior or current major depression\n- Any illness or prior/ongoing treatment that in the opinion of the investigators would jeopardize the ability of the patient to tolerate autologous stem cell treatment\n- Prior or current psychiatric illness, mental deficiency or cognitive dysfunction influencing the patient ability to make an informed consent or comply with the treatment and follow-up phases of this protocol.\n- Pregnancy or risk of pregnancy (this includes patients that are unwilling to practice active contraception during the duration of the study), breastfeeding or lactation\n- Known hypersensitivity against paracetamol, codein or xylocain\n- Diagnosis or strong suspicion of polyneuropathy\n- Prior or current alcohol or drug dependencies\n- Inability to give informed consent\n- Any ongoing infection, including Tbc, CMV, EBV, HSV, VZV, hepatitis virus, toxoplasmosis, HIV or syphilis infections, as well as heaptitis B surface antigen positivity and/or hepatitis C PCR positivity\n- Current immunomodulatory/immunosuppressive treatment\n- Immunomodulatory/immunosuppressive treatment within 6 months prior to inclusion. This includes, but is not restricted to treatment with natalizumab, fingolimod, dimetylfumurat, glatiramer acetate, interferon beta medications, teriflunomide, and siponimod.\n- Treatment with kladribin, ocrelizumab, rituximab, and alemtuzumab within 12 months prior to inclusion\n- Treatment with hematopoietic stem cell therapy within 12 months prior to inclusion\n- Treatment with glucocorticoids or ACTH within three months prior to start of inclusion\n- Having experienced an MS relapse within 2 years prior to study inclusion"}

Primary endpoints

• {"endpoint_text":"- Difference in CEP (VEP+SEP+MEP) at 6 months as compared to baseline between MSCs treatment vs. placebo (arm A vs. arm B)","definition_or_measurement_approach":"CEP defined as the composite of VEP (visual evoked potentials), SEP (somatosensory evoked potentials), and MEP (motor evoked potentials); measured as the difference in CEP at 6 months compared to baseline between MSC treatment and placebo (arm A vs. arm B)."}

Secondary endpoints

• {"endpoint_text":"- Difference in CEP at 12 months (study treatment 1 vs. study treatment 2)","definition_or_measurement_approach":"Measured as the difference in CEP between study treatment 1 and study treatment 2 at 12 months."}
• {"endpoint_text":"- Difference in VEP at 6 months (arm A vs. arm B)","definition_or_measurement_approach":"Measured as the difference in VEP between arm A and arm B at 6 months."}
• {"endpoint_text":"- Difference in VEP at 12 months (study treatment 1 vs. study treatment 2)","definition_or_measurement_approach":"Measured as the difference in VEP between study treatment 1 and study treatment 2 at 12 months."}
• {"endpoint_text":"- Difference in SEP at 6 months (arm A vs. arm B)","definition_or_measurement_approach":"Measured as the difference in SEP between arm A and arm B at 6 months."}
• {"endpoint_text":"- Difference in SEP at 12 months (study treatment 1 vs. study treatment 2)","definition_or_measurement_approach":"Measured as the difference in SEP between study treatment 1 and study treatment 2 at 12 months."}
• {"endpoint_text":"- Difference in MEP at 6 months (arm A vs. arm B)","definition_or_measurement_approach":"Measured as the difference in MEP between arm A and arm B at 6 months."}
• {"endpoint_text":"- Difference in MEP at 12 months (study treatment 1 vs. study treatment 2)","definition_or_measurement_approach":"Measured as the difference in MEP between study treatment 1 and study treatment 2 at 12 months."}
• {"endpoint_text":"- Difference in EDSS at 6 months (arm A vs. arm B)","definition_or_measurement_approach":"Measured as the difference in Expanded Disability Status Scale (EDSS) score between arm A and arm B at 6 months."}
• {"endpoint_text":"- Difference in EDSS at 12 months (study treatment 1 vs. study treatment 2)","definition_or_measurement_approach":"Measured as the difference in EDSS score between study treatment 1 and study treatment 2 at 12 months."}
• {"endpoint_text":"- Difference in MRI T2-weighted hyperintense lesion volume at 6 months (arm A vs. arm B)","definition_or_measurement_approach":"Measured as the difference in MRI T2-weighted hyperintense lesion volume between arm A and arm B at 6 months."}
• {"endpoint_text":"- Difference in MRI T2-weighted hyperintense lesion volume at 12 months (study treatment 1 vs. study treatment 2)","definition_or_measurement_approach":"Measured as the difference in MRI T2-weighted hyperintense lesion volume between study treatment 1 and study treatment 2 at 12 months."}
• {"endpoint_text":"- Difference in MRI T1-weighted hypointense lesion volume at 6 months (arm A vs. arm B)","definition_or_measurement_approach":"Measured as the difference in MRI T1-weighted hypointense lesion volume between arm A and arm B at 6 months."}
• {"endpoint_text":"- Difference in MRI T1-weighted hypointense lesion volume at 12 months (study treatment 1 vs. study treatment 2)","definition_or_measurement_approach":"Measured as the difference in MRI T1-weighted hypointense lesion volume between study treatment 1 and study treatment 2 at 12 months."}
• {"endpoint_text":"- Difference in brain volume at 6 months (arm A vs. arm B)","definition_or_measurement_approach":"Measured as the difference in brain volume between arm A and arm B at 6 months."}
• {"endpoint_text":"- Difference in brain volume at 12 months (study treatment 1 vs. study treatment 2)","definition_or_measurement_approach":"Measured as the difference in brain volume between study treatment 1 and study treatment 2 at 12 months."}
• {"endpoint_text":"- Difference in visual function (visual acuity, visual field, color vision and contrast sensitivity) at 6 months (arm A vs. arm B)","definition_or_measurement_approach":"Measured as differences in visual function metrics (visual acuity, visual field, color vision, contrast sensitivity) between arm A and arm B at 6 months."}
• {"endpoint_text":"- Difference in visual function (visual acuity, visual field, color vision and contrast sensitivity) at 12 months (study treatment 1 vs. study treatment 2)","definition_or_measurement_approach":"Measured as differences in visual function metrics between study treatment 1 and study treatment 2 at 12 months."}
• {"endpoint_text":"- Difference in retinal thickness measured with OCT at 6 months (arm A vs. arm B)","definition_or_measurement_approach":"Measured as the difference in retinal thickness by OCT between arm A and arm B at 6 months."}
• {"endpoint_text":"- Difference in retinal thickness measured with OCT at 12 months (study treatment 1 vs study treatment 2)","definition_or_measurement_approach":"Measured as the difference in retinal thickness by OCT between study treatment 1 and study treatment 2 at 12 months."}
• {"endpoint_text":"- Difference in Nine-Hole-Peg Test (9-HPT) score at 6 months (arm A vs. arm B)","definition_or_measurement_approach":"Measured as the difference in 9-HPT score between arm A and arm B at 6 months."}
• {"endpoint_text":"- Difference in Nine-Hole-Peg Test (9-HPT) score at 12 months (study treatment 1 vs. study treatment 2)","definition_or_measurement_approach":"Measured as the difference in 9-HPT score between study treatment 1 and study treatment 2 at 12 months."}
• {"endpoint_text":"- Difference in Timed 25 Foot Walk (T25FW) score at 6 months (arm A vs. arm B)","definition_or_measurement_approach":"Measured as the difference in T25FW score between arm A and arm B at 6 months."}
• {"endpoint_text":"- Difference in Timed 25 Foot Walk (T25FW) score at 12 months (study treatment 1 vs. study treatment 2)","definition_or_measurement_approach":"Measured as the difference in T25FW score between study treatment 1 and study treatment 2 at 12 months."}
• {"endpoint_text":"- Difference in the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS), European Quality of Life 5 dimensions (EQ-5D-5L), Multiple Sclerosis Impact Scale (MSIS) and Fatigue severity scale (FSS) score at 6 months (arm A vs. arm B)","definition_or_measurement_approach":"Measured as differences in BICAMS, EQ-5D-5L, MSIS and FSS scores between arm A and arm B at 6 months."}
• {"endpoint_text":"- Difference in the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS), European Quality of Life 5 dimensions (EQ-5D-5L), Multiple Sclerosis Impact Scale (MSIS) and Fatigue severity scale (FSS) score at 12 months (study treatment 1 vs. study treatment 2)","definition_or_measurement_approach":"Measured as differences in BICAMS, EQ-5D-5L, MSIS and FSS scores between study treatment 1 and study treatment 2 at 12 months."}
• {"endpoint_text":"- Difference in serum neurofilament light chain and GFAP at 6 months (arm A vs. arm B)","definition_or_measurement_approach":"Measured as difference in serum neurofilament light chain and GFAP concentrations between arm A and arm B at 6 months."}
• {"endpoint_text":"- Difference in serum neurofilament light chain and GFAP at 12 monhts (study treatment 1 vs. study treatment 2)","definition_or_measurement_approach":"Measured as difference in serum neurofilament light chain and GFAP concentrations between study treatment 1 and study treatment 2 at 12 months."}
• {"endpoint_text":"- Intraindividual CEP (longitudinal) between study treatment 1 vs. study treatment 2 in each patient","definition_or_measurement_approach":"Within-patient longitudinal comparison of CEP between study treatment 1 and study treatment 2."}
• {"endpoint_text":"- Rate and nature of adverse- and serious adverse events during 18 months of follow up","definition_or_measurement_approach":"Safety assessed as the rate and characterization of adverse events and serious adverse events over 18 months of follow-up."}
• {"endpoint_text":"- Clinical relevant changes in vital signs during 18 months of follow up","definition_or_measurement_approach":"Assessment of clinically relevant changes in vital signs over 18 months of follow-up."}
• {"endpoint_text":"- Clinical relevant changes on physical examinations during 18 months of follow up","definition_or_measurement_approach":"Assessment of clinically relevant changes on physical examinations over 18 months of follow-up."}
• {"endpoint_text":"- Clinical relevant changes in clinical laboratory results during 18 months of follow up","definition_or_measurement_approach":"Assessment of clinically relevant changes in clinical laboratory results over 18 months of follow-up."}

Norway

Earliest CTIS Part Ii Submission Date

22-04-2024

Latest Decision Or Authorization Date

30-04-2024

Processing Time Days

8

Number Of Sites

4

Number Of Participants

18

Primary sponsor

Full Name

Helse Bergen HF

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Norway