Nervous System Diseases

Immune System Diseases

All Conditions

Symptoms and General Pathology

Neoplasms

Rare Diseases

Multiple Sclerosis

Multiple Sclerosis, Chronic Progressive

Sclerosis

Neoplasm Metastasis

Multiple Sclerosis, Relapsing-Remitting

Autoimmune Diseases

Demyelinating Autoimmune Diseases, CNS

Autoimmune Diseases of the Nervous System

Demyelinating Diseases

Neoplastic Processes

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Antineoplastic Agents

All Drugs and Chemicals

Ofatumumab

Prospective observational cohort study. There is no treatment allocation.

Kesimpta

Novartis Pharmaceuticals

This study is an uncontrolled, central registration system, open-label, multicenter observational study in patients using Kesimpta for the labeled indication.

This is a primary data collection-based special drug-use surveillance to be conducted in accordance with the GPSP ordinance.

Observational period will last 24 months from the start of treatment with Kesimpta.

Special Drug-use Surveillance for Kesimpta for s.c. Injection 20 mg Pen

Special Drug-use Surveillance for Kesimpta for s.c. Injection 20 mg Pen (Relapsing-remitting Multiple Sclerosis and Active Secondary Progressive Multiple Sclerosis)

An adverse event (AE) is any untoward medical occurrence experienced by a patient administered a medicinal product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not related to the medicinal product(s).

A SAE is defined as an adverse event which:

* Is fatal or life-threatening
* Results in persistent or significant disability/incapacity
* Constitutes a congenital anomaly/birth defect
* Requires inpatient hospitalization or prolongation of existing hospitalization, unless hospitalization is for:

  * Routine treatment or monitoring of the indication under study, not associated with any deterioration in condition
  * Elective or pre-planned treatment for a pre-existing condition that is unrelated to the indication under study and has not worsened since the start of treatment with Kesimpta
  * Social reasons and respite care in the absence of any deterioration in the patient's general condition
* Is medically significant, i.e., events that jeopardize the patient or may require medical or surgical intervention to prevent one of the outcomes listed above.

An adverse reaction is defined as an adverse event that is suspected by the investigator to be causally related to Kesimpta or whose causality is not recorded.

The investigator will comprehensively assess the symptom changes in relapsing-remitting Multiple Sclerosis (MS) and active Secondary Progressive Multiple Sclerosis (SPMS), rating the changes as "very much improved", "improved", "unchanged", "worsening" or "not assessable" in comparison with the symptoms at the start of this drug, and record the results in the Case report forms (CRFs).

EDSS is a method of quantifying disability in multiple sclerosis (MS) and monitoring changes in the level of disability over time. The scale ranges from 0 (being normal neurological exam and no disability in any functional system) up to 10 (death due to MS). Confirmed disability worsening on EDSS continuing for ≥ 3 months and ≥ 6 months (3mCDW, 6mCDW)

EDSS is a method of quantifying disability in multiple sclerosis (MS) and monitoring changes in the level of disability over time. The scale ranges from 0 (being normal neurological exam and no disability in any functional system) up to 10 (death due to MS). Confirmed improvement on EDSS continuing for ≥ 6 months (6mCDI)

The investigator will record, in the Case report forms (CRFs), the numbers of gadolinium (Gd)-enhancing lesions on MRI

Relapse: Occurrence of new neurological abnormalities or pre-existing neurological abnormalities in stable state or remission occurring at least 30 days after the occurrence of the previous clinical demyelination event that continues at least for 24 hours without pyrexia and infection.

NEDA-3 assessments: no relapse, no new/enlarged MRI lesion, no disability progression on EDSS

Antipyretics

Analgesics

Antirheumatic Agents

Anti-Inflammatory Agents

Hematinics

Antiemetics

Neuroprotective Agents

Gastrointestinal Agents

Anti-Infective Agents

Anti-Allergic Agents

Dermatologic Agents

Acetaminophen

Rituximab

Prednisolone

Liver Extracts

Methylprednisolone

Carbamide Peroxide

Methylprednisolone Acetate

Methylprednisolone Hemisuccinate

Prednisolone acetate

Prednisolone hemisuccinate

Prednisolone phosphate

Glatiramer Acetate

(T,G)-A-L

Chlorpheniramine

Antineoplastic Agents, Immunological

Immunologic Factors

Adjuvants, Immunologic

Immunosuppressive Agents

Patients in this group will receive 1g of rituximab in 500 cc normal saline serum through intravenous infusion as one treatment course. The treatment course will be repeated in 6 months. Along with rituximab, 100 mg methylprednisolone, 10 mg chlorpheniramine, and 500 mg acetaminophen will also be injected to decrease side effects of rituximab.

Patients in this group will receive 40 mg of glatiramer acetate three times per week through subcutaneous injection.

Patients will receive 1 g of rituximab (two vials of Zytux 500 mg/50 ml) in 500 cc normal saline serum through intravenous infusion as one treatment cycle. This cycle will be repeated every 6 months. Along with rituximab, patients will receive 100 mg of methylprednisolone, 10 mg of chlorpheniramine, and 500 mg of acetaminophen. Before each cycle, patients will be evaluated regarding complete blood count (CBC)-diff, blood urea nitrogen (BUN), Cr, and liver function tests.

Patients will receive 40 mg of glatiramer acetate three times per week through subcutaneous injection. Patients will undergo electrocardiography before starting the treatment to find any abnormal finding. Also, lab tests will be checked for them prior to the treatment, including CBC-diff, BUN, Cr, and liver function tests.

Vahid Shaygannejad, M.D.

The purpose of this study is to compare expanded disability status scale, annualized relapse rate, Gad-enhanced brain lesions, and side effects after administration of rituximab and glatiramer acetate among patients with active secondary progressive multiple sclerosis during a one year follow up through a randomized clinical trial.

Multiple sclerosis (MS) is an autoimmune inflammatory demyelinative disease of central nervous system. Active secondary progressive MS means progressive accumulation of disability after an initial relapsing course which is also associated with clinical relapses and/or new/enlarged Gad-enhanced brain lesions. This form of the disease leads to high rates of morbidity and mortality among patients. Different immunosuppressive and immunomodulatory agents are recommended by researchers to decrease relapses and improve disability among MS patients. The effect of these medications on different phenotypes of MS are mostly investigated solely and very small number of comparative studies are conducted to evaluate the superiority of these medications on each other.

Glatiramer acetate is one of the known MS medications which is being used to control relapses from a long time ago and different clinical trials have shown its partial efficacy among MS patients. On the other hand, rituximab is one of the medications which is recently suggested for treatment of MS and currently phase II clinical trials are conducted to evaluate the efficacy of this medication among patients. As previously stated, there is a lack of clinical trials to compare the efficacy of suggested medications among secondary progressive patients. To fill this gap, we aimed to compare the efficacy of these two medications on disability, annualized relapse rate, and Gad-enhanced brain lesions among patients with active secondary progressive MS through a randomized clinical trial during a one-year follow-up period.

Comparison of Clinical Effects of Rituximab and Glatiramer Acetate in Secondary Progressive Multiple Sclerosis Patients

Comparison of Expanded Disability Status Scale, Gad-enhanced Brain Lesions, Annualized Relapse Rate, and Side Effects Between Active Secondary Progressive Multiple Sclerosis Patients on Rituximab and Glatiramer Acetate

We may share the individual participant data (anonymously) on request of qualified investigators.

expanded disability status scale will be measured in the baseline and after 12 months of intervention. This scale measures the disability of patients with a score, ranging from 0 (normal neurological exam) to 10 (death due to MS). This score is assigned to the patient by the neurologist and after neurological examination. The patient will be given a score in this scale according to the observed disability. The scores will be compared at the end of study.

adverse drug reactions will be observed closely and reported during the intervention. We will compare the number of adverse drug reactions in two groups. Also, adverse drug reactions will be described by details in each group.

patients will undergo brain MRI before and after the study and number of Gad-enhanced brain lesions will compared before and after intervention.

annualized relapse rate will be measured in the baseline (according to patients' history in the last year) and after 12 months of intervention.

Isfahan University of Medical Sciences

Professor of Neurology

Siponimod

Prospective observational cohort study. There is no treatment allocation. Patients will be invited to participate in the study after the independent decision by physician and patient to start siponimod treatment as routine clinical care.

siponimod

This is an observational, multicenter, single-arm, prospective study conducted in Italy

Primary data will be collected over a period of three years. Medical history of participants will be collected including EDSS, MRI outcomes, relapses and previous medication to allow the estimation of the effects of siponimod treatment on an individual basis.

Impact of Mayzent on aSPMS Patients in a Long-term NIS in Italy

Impact of Mayzent (Siponimod) on Active Secondary Progressive Multiple Sclerosis Patients in a Long-term Non-interventional Study in Italy

Confirmed disability progression (CDP) is defined as a ≥1.0-point worsening of Expanded Disability Status Scale (EDSS) score from ≤5.0 baseline or a 0.5-point worsening from \>5.0 baseline for at least 6 months OR a ≥4.0-point confirmed cognitive worsening (CCW) from baseline of Symbol Digit Modalities Test (SDMT) for at least 6 months.

ARR is the number of relapses during the period / person-years of subject Person-years for subject = period (in days) / 365.25

Number of new/newly enlarging T2-hyperintense lesions and number of new 1 gadolinium-enhancing (Gd+) lesions is collected

Expanded Disability Status Scale (EDSS) score is composed of the overall impression and individual scores of the following functional systems: cognition, mood, fatigue, vision, brain stem, upper extremities, lower extremities, bladder-intestinal function, sexuality. Scores are on a scale of 0 (healthy) to 10 (death from MS) with 0.5 unit increments

EDSS trend is measured by differentiating patients who stabilize from those who experience an increase of EDSS score (increment of ≥1 or ≥0.5 point if baseline EDSS was ≤5.0 or ˃5.0, respectively). Moreover, patients with progression will be categorized as patients with continuous disability accrual (CDA) or one-step worsening (OneS-wors), defined as:

* OneS-wors: the occurrence of one single episode of confirmed EDSS deterioration.
* CDA: occurrence of at least two episodes of OneS-wors associated with continuous disability progression between at least two time points.

NEDA-3 is defined as no Confirmed disability progression (CDP), no confirmed relapse and absence of T1 gadolinium-enhancing (Gd+) lesions.

The UKNDS is a questionnaire for recording impairments in MS from the patient's perspective and considers 12 functional systems: perception and thinking, mood, vision, speech and communication, swallowing, arm and hand function, walking ability, bladder function, bowel function, fatigue, sexuality, pain, cramps and others. Answering the questions results in a score of 0 (no disability) to 60 (maximum disability). This questionnaire will be completed by the patients during site visits.

The FSMC is a patient questionnaire for the clarification of cognitive and motor fatigue, a typical symptom of MS (Penner et al., 2009), and considers a cognitive, motor and total score. Score ranges from 200 to 100, the greater the score the greater the impairment caused by fatigue.

The HADS has seven items each for depression and anxiety subscales. Scoring for each item ranges from zero to three, with three denoting highest anxiety or depression level. A total subscale score of \>8 points out of a possible 21 denotes considerable symptoms of anxiety or depression.

Calculations of scores: each of the 14 items is rated on a 4-point scale ('Yes, definitely', 'Yes, sometimes', 'No, not much' and 'No, not at all'). All items except 7 and 10 are scored as 'Yes, definitely' = 3 to 'No, not at all' = 0. Items 7 and 10 are scored as 'Yes, definitely' = 0 to 'No, not at all' = 3. The HADS consists of two sub-scores: the HAD-A for anxiety and HAD-D for depression; each sub-score ranges from 0 to 21 points; scores ≥11 indicate the presence of anxious or depressive disorders; scores between 8-10 points are borderline abnormal, and scores of ≤7 indicate that the disorder is not present.

The SDMT is a sensitive and specific test to investigate attention, concentration and information processing speed, which are typically impaired in cognitively impaired MS patients.

Nine numbers are shown paired with 9 corresponding individual symbols. Below this are further lines with symbols and empty boxes. The patients must assign the correct numbers to the symbols as quickly as possible. The number of correctly assigned numbers within 90 seconds gives the test score. The total duration of the test is about 5 minutes and scores range between 0 and 110 where higher scores indicate better result.

A deterioration of the SDMT score by ≥4 points is considered clinically relevant

The CGI scale represents a short, independent assessment by the treating physician of the overall condition of the patient.

It incorporates patient history, psychosocial circumstances, symptoms, behavior and the influence of symptoms on the patient's functional ability. The CGI consists of three different global measures and all three will be evaluated: Severity of illness (CGI-S) ranges from 0 to 7, Global Improvement (CGI-I) ranges from 0 to 7 and Efficacy index (CGI-E) ranges from 0 to 16. A higher score means a severe impact on the disease.

Number of relapse, number of relapse that affects the daily activities, number of relapse that required an hospitalization and number of treated relapse to be collected

Number of patients with presence of symptoms to be collected

The T25-FW is an objective and quantitative test of the lower extremities. The time in seconds it takes a patient to walk a distance of 25 feet (7.62 m) is measured. The patient should walk as quickly and safely as possible. This test is performed twice in a row and the mean value of the time required is documented in seconds. An improvement or deterioration of 20% is considered a significant change

This test examines manual dexterity. Patients must individually remove nine pegs from a flat dish with one hand and insert them into corresponding holes in a test board. The pegs are then placed back into the dish with the same hand. Two rounds are performed per hand and the average value of the time required is documented in seconds

The EQ-5D is a generic multidimensional measurement tool for describing health-related quality of life (EuroQol, 1999). The five domains of mobility, self-care ability, daily activities, pain/discomfort and anxiety/depression are considered. For each of the dimensions, the most appropriate answer from three given possibilities is selected (1=no problem, 2=moderate problem, 3=large problem). In addition, the patient marks the current state of health on a scale from 0 (worst conceivable state of health) to 100 (best conceivable state of health).

The TSQM-9 is a questionnaire to assess patient satisfaction with siponimod treatment. The TSQM-9 is a sound and valid measure of the major dimensions of patients' satisfaction with medication and also a good predictor of adherence across different types of medication and patient population.

Effectiveness, side effects, simplicity and overall satisfaction are all rated between 0 and 100. Higher values mean a worse condition. Responses to items are summed and transformed so that higher scores indicate greater satisfaction. Specifically, TSQM-9 scale scores are computed by adding the items loading on each domain. The lowest possible score is subtracted from the composite score and divided by the greatest possible score range. This provides a transformed score between 0 and 1 that is then multiplied by 100. If more than one item is missing from a subscale of the TSQM-9 for a particular patient, this subscale should be considered invalid for that respondent.

Exposure adjusted proportion of patients with adverse event (AE) or serious adverse event (SAE) per 100 subject-years to be collected

Discontinuation rates due to AE or other reasons to be collected

Proportion of patient who required first dose observation (FDO) when starting siponimod and the reason why

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Special Drug-use Surveillance for Kesimpta for s.c. Injection 20 mg Pen	NCT04940065	Relapsing-remit... Active Secondar...	Kesimpta	- 99 Years	Novartis
Comparison of Clinical Effects of Rituximab and Glatiramer Acetate in Secondary Progressive Multiple Sclerosis Patients	NCT03315923	Secondary Progr...	Rituximab Glatiramer Acet...	18 Years - 55 Years	Isfahan University of Medical Sciences
Impact of Mayzent on aSPMS Patients in a Long-term NIS in Italy	NCT05376579	Active Secondar...	siponimod	18 Years - 60 Years	Novartis
Impact of Mayzent on aSPMS Patients in a Long-term NIS in Italy	NCT05376579	Active Secondar...	siponimod	18 Years - 60 Years	Novartis

Spots Global Cancer Trial Database for active secondary progressive multiple sclerosis