Multiple Sclerosis, Relapsing Multiple Sclerosis, Advancing Multiple Sclerosis
Conditions
Keywords
Multiple sclerosis, Relapsing multiple sclerosis, Advancing multiple sclerosis, conversion, siponimod, adult, BAF312, disease modifying therapies, cognitive assessment, open-label
Brief summary
To assess safety and tolerability of patients converting from approved Relapsing Multiple Sclerosis (RMS) Disease Modifying Therapies (DMTs) to siponimod.
Detailed description
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.
Interventions
DRUGSiponimod
Siponimod 2mg tablets taken once daily
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open-label single arm study
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Signed informed consent. 2. Male or female aged 18 to 65 years (inclusive). 3. Patients with advancing RMS as defined by the principal investigator. 4. Prior history of relapsing MS (RMS), with or without progressive features, according to the 2010 Revised McDonald or Lublin criteria (Lublin et al, 2013). 5. EDSS score of \>/= 2.0 to 6.5 (inclusive). 6. Having been continuously treated with RMS Disease Modifying Therapies. Key
Exclusion criteria
1. Pregnant or nursing (lactating) women. 2. Patients with any medically unstable condition as determined by the investigator. 3. Certain cardiac risk factors defined in the protocol 4. History of hypersensitivity to the study drug or to drugs of similar chemical classes. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE) Related to Study Drug During the Treatment Period | From first dose of study drug up to 30 days after last dose of study drug (up to 7 months) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With at Least One Adverse Event (AE) | From first dose of study drug up to 30 days after last dose of study drug (up to 7 months) | AE is any untoward sign or symptom that occurs during the study treatment plus 30 days post treatment. |
| Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM-9) | Baseline up to Day 168 | 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. |
| Change in Heart Rate From Baseline to 6 Hours After First Treatment | From the first dose up to 6 hours | Heart rate was evaluated from the time of initial dose intake until 6 hours post dose intake via heart monitor. |
| 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 | From first dose of study drug up to 30 days after last dose of study drug (up to 7 months) | Patient retention was assessed over the study period. |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in the United States from 14 February 2019 to 06 July 2022.
Pre-assignment details
A total of 342 participants were screened of which 185 participants were enrolled to receive siponimod.
Participants by arm
| Arm | Count |
|---|---|
| Siponimod Participants received 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 started directly with 2 mg dose of siponimod. | 185 |
| Total | 185 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 15 |
| Overall Study | Guardian Decision | 1 |
| Overall Study | New Therapy for Study Indication | 1 |
| Overall Study | Patient Decision | 15 |
| Overall Study | Physician Decision | 4 |
| Overall Study | Protocol Deviation | 3 |
Baseline characteristics
| Characteristic | Siponimod |
|---|---|
| Age, Continuous | 46.5 years STANDARD_DEVIATION 10.35 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 39 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 145 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 25 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 157 Participants |
| Region of Enrollment United States | 185 Participants |
| Sex: Female, Male Female | 137 Participants |
| Sex: Female, Male Male | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 185 |
| other Total, other adverse events | 63 / 185 |
| serious Total, serious adverse events | 9 / 185 |
Outcome results
Primary
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.
Time frame: From first dose of study drug up to 30 days after last dose of study drug (up to 7 months)
Population: Safety set included all participants who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Siponimod | Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE) Related to Study Drug During the Treatment Period | 59 Participants |
Secondary
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.
Time frame: Baseline up to Day 168
Population: Safety set included all participants who received at least one dose of study treatment. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Siponimod | Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM-9) | Change From Baseline in Effectiveness | 13.5 score on a scale | Standard Deviation 25.64 |
| Siponimod | Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM-9) | Change From Baseline in Convenience | 15.6 score on a scale | Standard Deviation 25.52 |
| Siponimod | Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM-9) | Change From Baseline in Global Satisfaction | 15.3 score on a scale | Standard Deviation 27.9 |
Secondary
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.
Time frame: From the first dose up to 6 hours
Population: Safety set included all participants who received at least one dose of study treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Siponimod | Change in Heart Rate From Baseline to 6 Hours After First Treatment | 2.47 beats per minute (bpm) | Standard Deviation 12.169 |
Secondary
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.
Time frame: From first dose of study drug up to 30 days after last dose of study drug (up to 7 months)
Population: Safety set included all participants who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Siponimod | Number of Participants With at Least One Adverse Event (AE) | 138 Participants |
Secondary
Number of Participants With at Least One Hospitalization During the Treatment
Time frame: From first dose of study drug up to last dose of study drug (up to 6 months)
Population: Safety set included all participants who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Siponimod | Number of Participants With at Least One Hospitalization During the Treatment | 9 Participants |
Secondary
Patient Retention Reported as Number of Participants Who Completed the Study
Patient retention was assessed over the study period.
Time frame: From first dose of study drug up to 30 days after last dose of study drug (up to 7 months)
Population: Safety set included all participants who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Siponimod | Patient Retention Reported as Number of Participants Who Completed the Study | 146 Participants |