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

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

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

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis; Relapsing Multiple Sclerosis; Advancing Multiple Sclerosis
• Intervention / Treatment: Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 185
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • Guaynabo, Puerto Rico, 00968
    • Novartis Investigative Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Novartis Investigative Site
    • Cullman, Alabama, United States, 35058
      • Novartis Investigative Site
    • Homewood, Alabama, United States, 35209
      • Alabama Neurology Associates
  • Arizona
    • Tucson, Arizona, United States, 85718
      • Novartis Investigative Site
  • California
    • Fresno, California, United States, 93710
      • Novartis Investigative Site
    • Fullerton, California, United States, 92835
      • Novartis Investigative Site
    • Irvine, California, United States, 92617
      • Novartis Investigative Site
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Novartis Investigative Site
    • Denver, Colorado, United States, 80209
      • Novartis Investigative Site
    • Fort Collins, Colorado, United States, 80528
      • Novartis Investigative Site
  • Florida
    • Boca Raton, Florida, United States, 33487
      • Novartis Investigative Site
    • Bradenton, Florida, United States, 34205
      • Novartis Investigative Site
    • Clearwater, Florida, United States, 33761
      • MS & Neuromuscular Center of Excellence
    • Maitland, Florida, United States, 32751
      • Novartis Investigative Site
    • Miami, Florida, United States, 33136
      • Novartis Investigative Site
    • Ocala, Florida, United States, 34471
      • Novartis Investigative Site
    • Oldsmar, Florida, United States, 34677
      • Novartis Investigative Site
    • Orlando, Florida, United States, 32806
      • Novartis Investigative Site
    • Ormond Beach, Florida, United States, 32174
      • Novartis Investigative Site
    • Sarasota, Florida, United States, 34243
      • Novartis Investigative Site
    • Sunrise, Florida, United States, 33351
      • Novartis Investigative Site
    • Tampa, Florida, United States, 33612
      • Novartis Investigative Site
    • Vero Beach, Florida, United States, 32960
      • Novartis Investigative Site
  • Illinois
    • Flossmoor, Illinois, United States, 60422
      • Novartis Investigative Site
  • Indiana
    • Indianapolis, Indiana, United States, 46256
      • Novartis Investigative Site
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Novartis Investigative Site
    • Lexington, Kentucky, United States, 40509
      • Novartis Investigative Site
    • Lexington, Kentucky, United States, 40513
      • Novartis Investigative Site
  • Maryland
    • Rockville, Maryland, United States, 20854
      • Novartis Investigative Site
  • Michigan
    • Clinton Township, Michigan, United States, 48035
      • Novartis Investigative Site
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Novartis Investigative Site
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Novartis Investigative Site
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Novartis Investigative Site
  • North Carolina
    • Asheville, North Carolina, United States, 28806
      • Novartis Investigative Site
    • Greensboro, North Carolina, United States, 27405
      • Novartis Investigative Site
    • Raleigh, North Carolina, United States, 27607
      • Novartis Investigative Site
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Novartis Investigative Site
    • Cleveland, Ohio, United States, 44106-5028
      • Novartis Investigative Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Novartis Investigative Site
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Neurological Associates, LTD
    • Philadelphia, Pennsylvania, United States, 19141
      • Novartis Investigative Site
    • Willow Grove, Pennsylvania, United States, 19090
      • Novartis Investigative Site
  • South Carolina
    • Greer, South Carolina, United States, 29650
      • Novartis Investigative Site
    • Indian Land, South Carolina, United States, 29707
      • Novartis Investigative Site
  • Tennessee
    • Cordova, Tennessee, United States, 38018
      • Novartis Investigative Site
    • Johnson City, Tennessee, United States, 37604
      • Novartis Investigative Site
  • Texas
    • Round Rock, Texas, United States, 78681
      • Novartis Investigative Site
    • San Antonio, Texas, United States, 78258
      • Novartis Investigative Site
  • Virginia
    • Falls Church, Virginia, United States, 22043
      • Novartis Investigative Site
  • Washington
    • Kirkland, Washington, United States, 98034
      • Novartis Investigative Site
    • Seattle, Washington, United States, 98122
      • Novartis Investigative Site
    • Spokane, Washington, United States, 99202
      • Novartis Investigative Site
    • Tacoma, Washington, United States, 98405
      • Novartis Investigative Site
  • Wisconsin
    • Waukesha, Wisconsin, United States, 53188
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Siponimod; 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; Siponimod 2mg tablets taken once daily; Other Names: BAF312

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Patient Lay Trial Summary

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2019
• Primary Completion (Actual): July 6, 2022
• Study Completion (Actual): July 6, 2022

Study Registration Dates

• First Submitted: August 7, 2018
• First Submitted That Met QC Criteria: August 8, 2018
• First Posted (Actual): August 9, 2018

Study Record Updates

• Last Update Posted (Actual): June 20, 2024
• Last Update Submitted That Met QC Criteria: June 17, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: adult; Multiple sclerosis; Relapsing multiple sclerosis; open-label; siponimod; conversion; cognitive assessment; Advancing multiple sclerosis; BAF312; disease modifying therapies
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Sphingosine 1 Phosphate Receptor Modulators; Siponimod
• Other Study ID Numbers: CBAF312AUS02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No