Back to resultsSafety and Tolerability of Conversion From Oral, Injectable, or Infusion Disease Modifying Therapies to Dose-titrated Oral Siponimod (Mayzent) in Advancing RMS Patients (EXCHANGE)
Primary Purpose
Multiple Sclerosis, Relapsing Multiple Sclerosis, Advancing Multiple Sclerosis
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Siponimod
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Sclerosis focused on measuring Multiple sclerosis, Relapsing multiple sclerosis, Advancing multiple sclerosis, conversion, siponimod, adult, BAF312, disease modifying therapies, cognitive assessment, open-label
Eligibility Criteria
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.
Sites / Locations
- Novartis Investigative Site
- Novartis Investigative Site
- Alabama Neurology Associates
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- MS & Neuromuscular Center of Excellence
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Abington Neurological Associates, Ltd
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Siponimod
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
Number of Participants With at Least One Hospitalization During the Treatment
Patient Retention Reported as Number of Participants Who Completed the Study
Patient retention was assessed over the study period.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03623243
Brief Title
Safety and Tolerability of Conversion From Oral, Injectable, or Infusion Disease Modifying Therapies to Dose-titrated Oral Siponimod (Mayzent) in Advancing RMS Patients
Acronym
EXCHANGE
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
February 14, 2019 (Actual)
Primary Completion Date
July 6, 2022 (Actual)
Study Completion Date
July 6, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Model Description
Open-label single arm study
Masking
None (Open Label)
Allocation
N/A
Enrollment
185 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Siponimod
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Siponimod
Other Intervention Name(s)
BAF312
Intervention Description
Siponimod 2mg tablets taken once daily
Primary Outcome Measure Information:
Title
Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE) Related to Study Drug During the Treatment Period
Description
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)
Secondary Outcome Measure Information:
Title
Number of Participants With at Least One Adverse Event (AE)
Description
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)
Title
Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM-9)
Description
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
Title
Change in Heart Rate From Baseline to 6 Hours After First Treatment
Description
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
Title
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)
Title
Patient Retention Reported as Number of Participants Who Completed the Study
Description
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35209
Country
United States
Facility Name
Novartis Investigative Site
City
Cullman
State/Province
Alabama
ZIP/Postal Code
35058
Country
United States
Facility Name
Alabama Neurology Associates
City
Homewood
State/Province
Alabama
ZIP/Postal Code
35209
Country
United States
Facility Name
Novartis Investigative Site
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85718
Country
United States
Facility Name
Novartis Investigative Site
City
Fresno
State/Province
California
ZIP/Postal Code
93710
Country
United States
Facility Name
Novartis Investigative Site
City
Fullerton
State/Province
California
ZIP/Postal Code
92835
Country
United States
Facility Name
Novartis Investigative Site
City
Irvine
State/Province
California
ZIP/Postal Code
92617
Country
United States
Facility Name
Novartis Investigative Site
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80907
Country
United States
Facility Name
Novartis Investigative Site
City
Denver
State/Province
Colorado
ZIP/Postal Code
80209
Country
United States
Facility Name
Novartis Investigative Site
City
Fort Collins
State/Province
Colorado
ZIP/Postal Code
80528
Country
United States
Facility Name
Novartis Investigative Site
City
Boca Raton
State/Province
Florida
ZIP/Postal Code
33487
Country
United States
Facility Name
Novartis Investigative Site
City
Bradenton
State/Province
Florida
ZIP/Postal Code
34205
Country
United States
Facility Name
MS & Neuromuscular Center of Excellence
City
Clearwater
State/Province
Florida
ZIP/Postal Code
33761
Country
United States
Facility Name
Novartis Investigative Site
City
Maitland
State/Province
Florida
ZIP/Postal Code
32751
Country
United States
Facility Name
Novartis Investigative Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Novartis Investigative Site
City
Ocala
State/Province
Florida
ZIP/Postal Code
34471
Country
United States
Facility Name
Novartis Investigative Site
City
Oldsmar
State/Province
Florida
ZIP/Postal Code
34677
Country
United States
Facility Name
Novartis Investigative Site
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Novartis Investigative Site
City
Ormond Beach
State/Province
Florida
ZIP/Postal Code
32174
Country
United States
Facility Name
Novartis Investigative Site
City
Sarasota
State/Province
Florida
ZIP/Postal Code
34243
Country
United States
Facility Name
Novartis Investigative Site
City
Sunrise
State/Province
Florida
ZIP/Postal Code
33351
Country
United States
Facility Name
Novartis Investigative Site
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Novartis Investigative Site
City
Vero Beach
State/Province
Florida
ZIP/Postal Code
32960
Country
United States
Facility Name
Novartis Investigative Site
City
Flossmoor
State/Province
Illinois
ZIP/Postal Code
60422
Country
United States
Facility Name
Novartis Investigative Site
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46256
Country
United States
Facility Name
Novartis Investigative Site
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40503
Country
United States
Facility Name
Novartis Investigative Site
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40509
Country
United States
Facility Name
Novartis Investigative Site
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40513
Country
United States
Facility Name
Novartis Investigative Site
City
Rockville
State/Province
Maryland
ZIP/Postal Code
20854
Country
United States
Facility Name
Novartis Investigative Site
City
Clinton Township
State/Province
Michigan
ZIP/Postal Code
48035
Country
United States
Facility Name
Novartis Investigative Site
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Novartis Investigative Site
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89128
Country
United States
Facility Name
Novartis Investigative Site
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Novartis Investigative Site
City
Asheville
State/Province
North Carolina
ZIP/Postal Code
28806
Country
United States
Facility Name
Novartis Investigative Site
City
Greensboro
State/Province
North Carolina
ZIP/Postal Code
27405
Country
United States
Facility Name
Novartis Investigative Site
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27607
Country
United States
Facility Name
Novartis Investigative Site
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Facility Name
Novartis Investigative Site
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106-5028
Country
United States
Facility Name
Novartis Investigative Site
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Abington Neurological Associates, Ltd
City
Abington
State/Province
Pennsylvania
ZIP/Postal Code
19001
Country
United States
Facility Name
Novartis Investigative Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19141
Country
United States
Facility Name
Novartis Investigative Site
City
Willow Grove
State/Province
Pennsylvania
ZIP/Postal Code
19090
Country
United States
Facility Name
Novartis Investigative Site
City
Greer
State/Province
South Carolina
ZIP/Postal Code
29650
Country
United States
Facility Name
Novartis Investigative Site
City
Indian Land
State/Province
South Carolina
ZIP/Postal Code
29707
Country
United States
Facility Name
Novartis Investigative Site
City
Cordova
State/Province
Tennessee
ZIP/Postal Code
38018
Country
United States
Facility Name
Novartis Investigative Site
City
Johnson City
State/Province
Tennessee
ZIP/Postal Code
37604
Country
United States
Facility Name
Novartis Investigative Site
City
Round Rock
State/Province
Texas
ZIP/Postal Code
78681
Country
United States
Facility Name
Novartis Investigative Site
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78258
Country
United States
Facility Name
Novartis Investigative Site
City
Falls Church
State/Province
Virginia
ZIP/Postal Code
22043
Country
United States
Facility Name
Novartis Investigative Site
City
Kirkland
State/Province
Washington
ZIP/Postal Code
98034
Country
United States
Facility Name
Novartis Investigative Site
City
Seattle
State/Province
Washington
ZIP/Postal Code
98122
Country
United States
Facility Name
Novartis Investigative Site
City
Spokane
State/Province
Washington
ZIP/Postal Code
99202
Country
United States
Facility Name
Novartis Investigative Site
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98405
Country
United States
Facility Name
Novartis Investigative Site
City
Waukesha
State/Province
Wisconsin
ZIP/Postal Code
53188
Country
United States
Facility Name
Novartis Investigative Site
City
Guaynabo
ZIP/Postal Code
00968
Country
Puerto Rico
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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
Learn more about this trial
Safety and Tolerability of Conversion From Oral, Injectable, or Infusion Disease Modifying Therapies to Dose-titrated Oral Siponimod (Mayzent) in Advancing RMS Patients
We'll reach out to this number within 24 hrs