We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05376579
Recruitment Status : Recruiting
First Posted : May 17, 2022
Last Update Posted : September 16, 2022
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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

Condition or disease Intervention/treatment
Active Secondary Progressive Multiple Sclerosis Other: siponimod

Detailed Description:
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.

Layout table for study information
Study Type : Observational
Estimated Enrollment : 200 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Impact of Mayzent (Siponimod) on Active Secondary Progressive Multiple Sclerosis Patients in a Long-term Non-interventional Study in Italy
Actual Study Start Date : June 17, 2022
Estimated Primary Completion Date : June 30, 2026
Estimated Study Completion Date : June 30, 2026


Group/Cohort Intervention/treatment
siponimod
patients treated with siponimod
Other: 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.
Other Name: mayzent




Primary Outcome Measures :
  1. Proportion of patients with six-month CDP during 36 months of treatment [ Time Frame: 36 months ]
    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.


Secondary Outcome Measures :
  1. Annualized relapse rate (ARR) [ Time Frame: Month 12, month 24 and month 36 ]
    ARR is the number of relapses during the period / person-years of subject Person-years for subject = period (in days) / 365.25

  2. Number of new/newly enlarging T2 [neT2] and Gd+T1 lesions [ Time Frame: Baseline, month 3, month 6, month 12, month 18, month 24, month 30 and month 36 ]
    Number of new/newly enlarging T2-hyperintense lesions and number of new 1 gadolinium-enhancing (Gd+) lesions is collected

  3. Expanded Disability Status Scale scores [ Time Frame: Month 12, month 24 and month 36 ]
    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

  4. Expanded Disability Status Scale trend [ Time Frame: Month 12, month 24 and month 36 ]

    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.

  5. Proportion of patients with No Evidence of Disease Activity (NEDA)-3 [ Time Frame: Month 12, month 24 and month 36 ]
    NEDA-3 is defined as no Confirmed disability progression (CDP), no confirmed relapse and absence of T1 gadolinium-enhancing (Gd+) lesions.

  6. UK Neurological Disability Scale (UKNDS) [ Time Frame: Baseline, month 3, month 6, month 12, month 18, month 24, month 30 and month 36 ]
    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.

  7. Fatigue Scale for Motor and Cognitive Functions (FSMC) [ Time Frame: Baseline, month 3, month 6, month 12, month 18, month 24, month 30 and month 36 ]
    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.

  8. Hospital Anxiety and Depression Scale (HADS) [ Time Frame: Baseline, month 3, month 6, month 12, month 18, month 24, month 30 and month 36 ]

    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.


  9. Symbol Digit Modality test (SDMT) [ Time Frame: Baseline, month 3, month 6, month 12, month 18, month 24, month 30 and month 36 ]

    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


  10. Clinical Global Impression (CGI) [ Time Frame: Baseline, month 3, month 6, month 12, month 18, month 24, month 30 and month 36 ]

    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.


  11. MS activity status (MS-AS) - number of relapse [ Time Frame: Baseline, month 3, month 6, month 12, month 18, month 24, month 30 and month 36 ]
    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

  12. MS activity status (MS-AS) - Number of patients with presence of symptoms [ Time Frame: Baseline, month 3, month 6, month 12, month 18, month 24, month 30 and month 36 ]
    Number of patients with presence of symptoms to be collected

  13. T25-foot-walk [ Time Frame: Baseline, month 3, month 6, month 12, month 18, month 24, month 30 and month 36 ]
    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

  14. 9-Hole peg test [ Time Frame: Baseline, month 3, month 6, month 12, month 18, month 24, month 30 and month 36 ]
    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

  15. EQ-5D: EuroQol five-dimensional [ Time Frame: Baseline, month 3, month 6, month 12, month 18, month 24, month 30 and month 36 ]
    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).

  16. TSQM-9: Treatment Satisfaction Questionnaire for Medication [ Time Frame: Baseline, month 3, month 6, month 12, month 18, month 24, month 30 and month 36 ]

    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.


  17. Exposure adjusted proportion of patients with adverse event (AE) or serious adverse event (SAE) per 100 subject-years [ Time Frame: Up to 36 months ]
    Exposure adjusted proportion of patients with adverse event (AE) or serious adverse event (SAE) per 100 subject-years to be collected

  18. Discontinuation rates due to AE or other reasons [ Time Frame: Up to 36 months ]
    Discontinuation rates due to AE or other reasons to be collected

  19. Proportion of patient who required FDO when starting siponimod and the reason why [ Time Frame: Baseline ]
    Proportion of patient who required first dose observation (FDO) when starting siponimod and the reason why



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
patients in Italy with active SPMS treated with siponimod as per label and local clinical practice.
Criteria

Inclusion Criteria:

  1. Signed informed consent: patient must provide written informed consent before any study assessment is performed.
  2. Male/female participants aged between 18 and 60.
  3. Documented diagnosis of active SPMS.
  4. Siponimod treatment as routine medical care: patients newly treated with siponimod (starting not more than 7 days before baseline visit), for whom the decision to start treatment has already been taken independently of study inclusion based on clinical practice and according to SmPC and AIFA criteria, and who successfully qualified for treatment with siponimod (i.e. passed the screening procedure mandated by the SmPC and Risk Management Plan (RMP) for this treatment, including genotyping for CYP2C9 to determine CYP2C9 metaboliser status).

Exclusion Criteria:

  1. Patients treated outside the approved siponimod label or with any controindication indicated in the SmPC.
  2. Pregnant or lactating women.
  3. Patients with any clinical condition that may interfere with the subject's ability to cooperate and comply with the study procedures based on the investigator's judgement.
  4. Current participation in an interventional trial.
  5. Treatment with siponimod prior to inclusion in this study (siponimod can be started not more than 7 days before baseline visit).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05376579


Contacts
Layout table for location contacts
Contact: Novartis Pharmaceuticals +41613241111 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals

Locations
Layout table for location information
Italy
Novartis Investigative Site Recruiting
L Aquila, AQ, Italy, 67100
Novartis Investigative Site Recruiting
Bergamo, BG, Italy, 24128
Novartis Investigative Site Recruiting
Bologna, BO, Italy, 40139
Novartis Investigative Site Recruiting
Brescia, BS, Italy, 25123
Novartis Investigative Site Recruiting
Como, CO, Italy, 22100
Novartis Investigative Site Recruiting
Foggia, FG, Italy, 71100
Novartis Investigative Site Recruiting
Messina, ME, Italy, 98121
Novartis Investigative Site Recruiting
Milano, MI, Italy, 20133
Novartis Investigative Site Recruiting
Palermo, PA, Italy, 90127
Novartis Investigative Site Recruiting
Pavia, PV, Italy, 27100
Novartis Investigative Site Recruiting
Roma, RM, Italy, 00133
Novartis Investigative Site Recruiting
Roma, RM, Italy, 00152
Novartis Investigative Site Recruiting
Roma, RM, Italy, 00189
Novartis Investigative Site Recruiting
Vicenza, VI, Italy, 36100
Novartis Investigative Site Recruiting
Novara, Italy, 28100
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Layout table for investigator information
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Layout table for additonal information
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT05376579    
Other Study ID Numbers: CBAF312AIT04
First Posted: May 17, 2022    Key Record Dates
Last Update Posted: September 16, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Secondary Progressive Multiple Sclerosis
aSPMS
NIS
Italy
Mayzent
siponimod
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasm Metastasis
Multiple Sclerosis
Multiple Sclerosis, Chronic Progressive
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Neoplastic Processes
Neoplasms
Siponimod
Sphingosine 1 Phosphate Receptor Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs