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

NCT03623243 | Completed Phase 3 Results FDA Drug

• 1 other identifier: CBAF312AUS02
• Study Type: interventional
• Target: 185
• Locations: 2 countries
• Sites: 55

Brief Summary

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

Conditions

Multiple Sclerosis; Relapsing Multiple Sclerosis; Advancing Multiple Sclerosis

Keywords

Multiple sclerosis; Relapsing multiple sclerosis; Advancing multiple sclerosis; conversion; siponimod; adult; BAF312; disease modifying therapies; cognitive assessment; open-label

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• 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)

• Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM-9)

  Baseline up to Day 168

• Change in Heart Rate From Baseline to 6 Hours After First Treatment

  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

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

Study Arms (1)

Siponimod

EXPERIMENTAL

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

Interventions

Siponimod DRUG

Siponimod 2mg tablets taken once daily

Also known as: BAF312

Siponimod

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (55)

Novartis Investigative Site

Birmingham, Alabama, 35209, United States

Location

Novartis Investigative Site

Cullman, Alabama, 35058, United States

Location

Alabama Neurology Associates

Homewood, Alabama, 35209, United States

Location

Novartis Investigative Site

Tucson, Arizona, 85718, United States

Location

Novartis Investigative Site

Fresno, California, 93710, United States

Location

Novartis Investigative Site

Fullerton, California, 92835, United States

Location

Novartis Investigative Site

Irvine, California, 92617, United States

Location

Novartis Investigative Site

Colorado Springs, Colorado, 80907, United States

Location

Novartis Investigative Site

Denver, Colorado, 80209, United States

Location

Novartis Investigative Site

Fort Collins, Colorado, 80528, United States

Location

Novartis Investigative Site

Boca Raton, Florida, 33487, United States

Location

Novartis Investigative Site

Bradenton, Florida, 34205, United States

Location

MS & Neuromuscular Center of Excellence

Clearwater, Florida, 33761, United States

Location

Novartis Investigative Site

Maitland, Florida, 32751, United States

Location

Novartis Investigative Site

Miami, Florida, 33136, United States

Location

Novartis Investigative Site

Ocala, Florida, 34471, United States

Location

Novartis Investigative Site

Oldsmar, Florida, 34677, United States

Location

Novartis Investigative Site

Orlando, Florida, 32806, United States

Location

Novartis Investigative Site

Ormond Beach, Florida, 32174, United States

Location

Novartis Investigative Site

Sarasota, Florida, 34243, United States

Location

Novartis Investigative Site

Sunrise, Florida, 33351, United States

Location

Novartis Investigative Site

Tampa, Florida, 33612, United States

Location

Novartis Investigative Site

Vero Beach, Florida, 32960, United States

Location

Novartis Investigative Site

Flossmoor, Illinois, 60422, United States

Location

Novartis Investigative Site

Indianapolis, Indiana, 46256, United States

Location

Novartis Investigative Site

Lexington, Kentucky, 40503, United States

Location

Novartis Investigative Site

Lexington, Kentucky, 40509, United States

Location

Novartis Investigative Site

Lexington, Kentucky, 40513, United States

Location

Novartis Investigative Site

Rockville, Maryland, 20854, United States

Location

Novartis Investigative Site

Clinton Township, Michigan, 48035, United States

Location

Novartis Investigative Site

St Louis, Missouri, 63110, United States

Location

Novartis Investigative Site

Las Vegas, Nevada, 89128, United States

Location

Novartis Investigative Site

Hackensack, New Jersey, 07601, United States

Location

Novartis Investigative Site

Asheville, North Carolina, 28806, United States

Location

Novartis Investigative Site

Greensboro, North Carolina, 27405, United States

Location

Novartis Investigative Site

Raleigh, North Carolina, 27607, United States

Location

Novartis Investigative Site

Cincinnati, Ohio, 45219, United States

Location

Novartis Investigative Site

Cleveland, Ohio, 44106-5028, United States

Location

Novartis Investigative Site

Oklahoma City, Oklahoma, 73104, United States

Location

Abington Neurological Associates, Ltd

Abington, Pennsylvania, 19001, United States

Location

Novartis Investigative Site

Philadelphia, Pennsylvania, 19141, United States

Location

Novartis Investigative Site

Willow Grove, Pennsylvania, 19090, United States

Location

Novartis Investigative Site

Greer, South Carolina, 29650, United States

Location

Novartis Investigative Site

Old Point Station, South Carolina, 29707, United States

Location

Novartis Investigative Site

Cordova, Tennessee, 38018, United States

Location

Novartis Investigative Site

Johnson City, Tennessee, 37604, United States

Location

Novartis Investigative Site

Round Rock, Texas, 78681, United States

Location

Novartis Investigative Site

San Antonio, Texas, 78258, United States

Location

Novartis Investigative Site

Falls Church, Virginia, 22043, United States

Location

Novartis Investigative Site

Kirkland, Washington, 98034, United States

Location

Novartis Investigative Site

Seattle, Washington, 98122, United States

Location

Novartis Investigative Site

Spokane, Washington, 99202, United States

Location

Novartis Investigative Site

Tacoma, Washington, 98405, United States

Location

Novartis Investigative Site

Waukesha, Wisconsin, 53188, United States

Location

Novartis Investigative Site

Guaynabo, 00968, Puerto Rico

Location

Related Publications (1)

• Fox RJ, Cohan S, Mao-Draayer Y, Weinstock-Guttman B, Cruz LA, Arnould S, Cox GM, Bar-Or A. Safety and tolerability of conversion to siponimod from other disease-modifying therapies in patients with advancing forms of relapsing MS: Results from the EXCHANGE study. Mult Scler. 2025 May;31(6):706-718. doi: 10.1177/13524585251330085. Epub 2025 Apr 18.

  PMID: 40248858 DERIVED

Related Links

• Patient Lay Trial Summary

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

siponimod

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+1 862 778 8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open-label single arm study

Study Record Dates

• First Submitted: August 7, 2018
• First Posted: August 9, 2018
• Study Start: February 14, 2019
• Primary Completion: July 6, 2022
• Study Completion: July 6, 2022
• Last Updated: June 20, 2024
• Results First Posted: July 20, 2023

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share

Locations

US (54); PR (1)