Safety and Tolerability of Conversion From Oral, Injectable, or Infusion Disease Modifying Therapies to Dose-titrated Oral Siponimod (Mayzent) in Advancing RMS Patients

Study Overview
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Brief Summary
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To assess safety and tolerability of patients converting from approved Relapsing Multiple Sclerosis (RMS) Disease Modifying Therapies (DMTs) to siponimod.

Detailed Description
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This is a 6-month, open-label, multi-center, single arm design, including advancing RMS patients, evaluating the overall safety and tolerability profile of converting from oral, injectable or infusion RMS DMTs to oral siponimod.

Official Title
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Exploring the Safety and Tolerability of Conversion From Oral, Injectable, or Infusion Disease Modifying Therapies to Dose-titrated Oral Siponimod (Mayzent) in Patients With Advancing Forms of Relapsing Multiple Sclerosis: A 6-month Open Label, Multi- Center Phase IIIb Study

Conditions
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Multiple Sclerosis, Relapsing Multiple Sclerosis, Advancing Multiple Sclerosis

Intervention / Treatment
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* Drug: Siponimod


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Signed informed consent. Male or female aged 18 to 65 years (inclusive). Patients with advancing RMS as defined by the principal investigator. Prior history of relapsing MS (RMS), with or without progressive features, according to the 2010 Revised McDonald or Lublin criteria (Lublin et al, 2013). EDSS score of >/= 2.0 to 6.5 (inclusive). Having been continuously treated with RMS Disease Modifying Therapies. Key Exclusion criteria: Pregnant or nursing (lactating) women. Patients with any medically unstable condition as determined by the investigator. Certain cardiac risk factors defined in the protocol History of hypersensitivity to the study drug or to drugs of similar chemical classes. Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open-label single arm study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Siponimod<br>Participants will receive titrated doses of siponimod tablets, orally, once daily of 0.25 mg on Day 2, 0.5 mg on Day 3, 0.75 mg on Day 4, 1.25 mg on Day 5, and maintenance dose of siponimod 2.0 mg tablets, orally, once daily from Day 6 up to 6 months. As of protocol amendment 3, participants entering the trial converting from fingolimod will start directly with 2 mg dose of siponimod. | Drug: Siponimod<br>* Siponimod 2mg tablets taken once daily<br>* Other names: BAF312;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE) Related to Study Drug During the Treatment Period | An Adverse Event (AE) is any untoward medical occurrence in a participant that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAEs are defined as the AEs started after the first dose of siponimod to 30 days after the date of the last actual administration, or events present prior to start of treatment but which increased in severity. TEAEs suspected to be related to study drug are reported. | From first dose of study drug up to 30 days after last dose of study drug (up to 7 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With at Least One Adverse Event (AE) | AE is any untoward sign or symptom that occurs during the study treatment plus 30 days post treatment. | From first dose of study drug up to 30 days after last dose of study drug (up to 7 months) | 
| Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM-9) | TSQM-9 measures participant satisfaction with the medication in 3 domains: Effectiveness, convenience, and global satisfaction. The scores were computed by adding items for each domain, i.e., 1 to 3 for effectiveness, 4 to 6 for convenience, and 7 to 9 for global satisfaction. The lowest possible score (1 for each item and 3 for all 3 subscales) was subtracted from the composite score and divided by the greatest possible score range. The greatest range was (7-1) x 3 items = 18 for effectiveness and convenience, and (5-1) x 3 items = 12 for global satisfaction. This provided a transformed score between 0 and 1 that was then multiplied by 100. TSQM-9 domain scores range from 0 to 100, with higher scores indicating greater satisfaction for that domain. A positive change from baseline indicates improvement. | Baseline up to Day 168 | 
| Change in Heart Rate From Baseline to 6 Hours After First Treatment | Heart rate was evaluated from the time of initial dose intake until 6 hours post dose intake via heart monitor. | From the first dose up to 6 hours | 
| Number of Participants With at Least One Hospitalization During the Treatment |  | From first dose of study drug up to last dose of study drug (up to 6 months) | 
| Patient Retention Reported as Number of Participants Who Completed the Study | Patient retention was assessed over the study period. | From first dose of study drug up to 30 days after last dose of study drug (up to 7 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple sclerosis, Relapsing multiple sclerosis, Advancing multiple sclerosis, conversion, siponimod, adult, BAF312, disease modifying therapies, cognitive assessment, open-label