Trial Outcomes & Findings for Safety and Tolerability of Conversion From Oral, Injectable, or Infusion Disease Modifying Therapies to Dose-titrated Oral Siponimod (Mayzent) in Advancing RMS Patients (NCT NCT03623243)

Last Updated: 2024-06-20

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

185 participants

Primary outcome timeframe

From first dose of study drug up to 30 days after last dose of study drug (up to 7 months)

Results posted on

2024-06-20

Participant Flow

Participants were enrolled at study sites in the United States from 14 February 2019 to 06 July 2022.

A total of 342 participants were screened of which 185 participants were enrolled to receive siponimod.

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	185
Overall Study Safety Set	185
Overall Study COMPLETED	146
Overall Study NOT COMPLETED	39

Reasons for withdrawal

Reasons for withdrawal
Measure	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.
Overall Study Adverse Event	15
Overall Study Guardian Decision	1
Overall Study New Therapy for Study Indication	1
Overall Study Protocol Deviation	3
Overall Study Physician Decision	4
Overall Study Patient Decision	15

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Siponimod n=185 Participants 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.
Age, Continuous	46.5 years STANDARD_DEVIATION 10.35 • n=5 Participants
Sex: Female, Male Female	137 Participants n=5 Participants
Sex: Female, Male Male	48 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	39 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	145 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	25 Participants n=5 Participants
Race (NIH/OMB) White	157 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	185 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Siponimod n=185 Participants 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.
Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE) Related to Study Drug During the Treatment Period	59 Participants

SECONDARY outcome

Timeframe: 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.

AE is any untoward sign or symptom that occurs during the study treatment plus 30 days post treatment.

Outcome measures

Outcome measures
Measure	Siponimod n=185 Participants 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.
Number of Participants With at Least One Adverse Event (AE)	138 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Siponimod n=97 Participants 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.
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
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
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 27.90

SECONDARY outcome

Timeframe: From the first dose up to 6 hours

Population: Safety set included all participants who received at least one dose of study treatment.

Heart rate was evaluated from the time of initial dose intake until 6 hours post dose intake via heart monitor.

Outcome measures

Outcome measures
Measure	Siponimod n=185 Participants 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.
Change in Heart Rate From Baseline to 6 Hours After First Treatment	2.47 beats per minute (bpm) Standard Deviation 12.169

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Siponimod n=185 Participants 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.
Number of Participants With at Least One Hospitalization During the Treatment	9 Participants

SECONDARY outcome

Timeframe: 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.

Patient retention was assessed over the study period.

Outcome measures

Outcome measures
Measure	Siponimod n=185 Participants 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.
Patient Retention Reported as Number of Participants Who Completed the Study	146 Participants

Adverse Events

Siponimod

Serious events: 9 serious events

Other events: 63 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Siponimod n=185 participants at risk 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.
General disorders Non-cardiac chest pain	0.54% 1/185 • From first dose of study drug up to 30 days after last dose of study drug (up to 7 months) Safety set included all participants who received at least one dose of study treatment.
Infections and infestations Appendicitis	0.54% 1/185 • From first dose of study drug up to 30 days after last dose of study drug (up to 7 months) Safety set included all participants who received at least one dose of study treatment.
Infections and infestations Cellulitis	0.54% 1/185 • From first dose of study drug up to 30 days after last dose of study drug (up to 7 months) Safety set included all participants who received at least one dose of study treatment.
Infections and infestations Pneumonia aspiration	0.54% 1/185 • From first dose of study drug up to 30 days after last dose of study drug (up to 7 months) Safety set included all participants who received at least one dose of study treatment.
Infections and infestations Pyelonephritis	0.54% 1/185 • From first dose of study drug up to 30 days after last dose of study drug (up to 7 months) Safety set included all participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Respiratory fume inhalation disorder	0.54% 1/185 • From first dose of study drug up to 30 days after last dose of study drug (up to 7 months) Safety set included all participants who received at least one dose of study treatment.
Nervous system disorders Cerebrovascular accident	0.54% 1/185 • From first dose of study drug up to 30 days after last dose of study drug (up to 7 months) Safety set included all participants who received at least one dose of study treatment.
Nervous system disorders Hemiparesis	0.54% 1/185 • From first dose of study drug up to 30 days after last dose of study drug (up to 7 months) Safety set included all participants who received at least one dose of study treatment.
Nervous system disorders Multiple sclerosis	0.54% 1/185 • From first dose of study drug up to 30 days after last dose of study drug (up to 7 months) Safety set included all participants who received at least one dose of study treatment.
Nervous system disorders Multiple sclerosis relapse	0.54% 1/185 • From first dose of study drug up to 30 days after last dose of study drug (up to 7 months) Safety set included all participants who received at least one dose of study treatment.
Renal and urinary disorders Tubulointerstitial nephritis	0.54% 1/185 • From first dose of study drug up to 30 days after last dose of study drug (up to 7 months) Safety set included all participants who received at least one dose of study treatment.
Vascular disorders Lymphoedema	0.54% 1/185 • From first dose of study drug up to 30 days after last dose of study drug (up to 7 months) Safety set included all participants who received at least one dose of study treatment.

Other adverse events

Other adverse events
Measure	Siponimod n=185 participants at risk 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.
Gastrointestinal disorders Nausea	8.1% 15/185 • From first dose of study drug up to 30 days after last dose of study drug (up to 7 months) Safety set included all participants who received at least one dose of study treatment.
General disorders Fatigue	7.0% 13/185 • From first dose of study drug up to 30 days after last dose of study drug (up to 7 months) Safety set included all participants who received at least one dose of study treatment.
Infections and infestations Urinary tract infection	8.6% 16/185 • From first dose of study drug up to 30 days after last dose of study drug (up to 7 months) Safety set included all participants who received at least one dose of study treatment.
Nervous system disorders Dizziness	7.0% 13/185 • From first dose of study drug up to 30 days after last dose of study drug (up to 7 months) Safety set included all participants who received at least one dose of study treatment.
Nervous system disorders Headache	13.5% 25/185 • From first dose of study drug up to 30 days after last dose of study drug (up to 7 months) Safety set included all participants who received at least one dose of study treatment.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: +1 862 778 8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER