Relapsing-remitting Multiple Sclerosis
Conditions
Keywords
Multiple Sclerosis, FTY720, Fingolimod
Brief summary
This study assessed the efficacy, safety, and tolerability of 2 doses of oral fingolimod (1.25 mg/day and 0.5 mg/day) compared to placebo in patients with relapsing-remitting multiple sclerosis (RRMS)
Interventions
Patients self-administered fingolimod 1.25 mg capsules orally once daily.
Patients self-administered fingolimod 0.5 mg capsules orally once daily.
DRUGPlacebo
Patients self-administered a fingolimod placebo capsule orally once daily.
Sponsors
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Male and female patients between ages 18-55 with a diagnosis of multiple sclerosis * Patients with a relapsing-remitting disease course * Patients with EDSS score of 0-5.5
Exclusion criteria
* Patients with other chronic disease of the immune system, malignancies, acute pulmonary disease, cardiac failure, etc. * Pregnant or nursing women Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Estimated Annualized Aggregate Relapse Rate (ARR) | Baseline to end of study (Month 24) | The ARR is defined as the number of confirmed relapses in a year. A relapse is defined as the appearance of a new or worsening of a previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding relapse. The abnormality must be present for at least 24 hours and occur in the absence of fever or infection. The annualized ARR for each treatment group was the mean of the annualized ARRs for all patients in the group calculated as the total number of confirmed relapses divided by the total number of days on study, multiplied by 365.25. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Free of Disability Progression at Month 24 Assessed With the Expanded Disability Status Scale (EDSS) | Baseline to end of study (Month 24) | EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) is calculated. Disability progression was determined by the following: One point increase from baseline in patients with baseline EDSS score from 0 to 5.0; or half a point increase in patients with baseline EDSS score of 5.5 or above. A 3-month confirmed disability progression required onset EDSS, 3-month confirming EDSS, and all EDSS in between to meet the disability progression criteria. Percent of free of disability progression was calculated using the Kaplan Meier method. |
| Number of New or Newly Enlarged T2 Lesions at Month 24 in Comparison With Baseline | Baseline to end of study (Month 24) | The number of new or newly enlarged T2 lesions at Month 24 in comparison to baseline was assessed with T2-weighted magnetic resonance image (MRI) scans. A T2-weighted MRI scan utilizes particular values of the echo time (TE) and the repetition time (TR) parameters of image acquisition. Inflammation and tissue damage are seen as bright areas in T2 images and are often referred to as T2 lesions. T2-weighted MRI scans are a sensitive way to evaluate the brain for demyelinating diseases, such as multiple sclerosis. |
Countries
Australia, Belgium, Canada, Czechia, Finland, France, Germany, Greece, Israel, Lithuania, Netherlands, Poland, Russia, Slovakia, South Africa, Sweden, Switzerland, Turkey (Türkiye), United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fingolimod 1.25 mg Patients self-administered fingolimod 1.25 mg capsules orally once daily. | 429 |
| Fingolimod 0.5 mg Patients self-administered fingolimod 0.5 mg capsules orally once daily. | 425 |
| Placebo Patients self-administered a fingolimod placebo capsule orally once daily. | 418 |
| Total | 1,272 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Abnormal laboratory value(s) | 20 | 9 | 1 |
| Overall Study | Abnormal test procedure result(s) | 2 | 1 | 1 |
| Overall Study | Adverse Event | 22 | 13 | 18 |
| Overall Study | Death | 1 | 0 | 2 |
| Overall Study | Lack of Efficacy | 13 | 6 | 25 |
| Overall Study | Lost to Follow-up | 3 | 5 | 7 |
| Overall Study | Protocol Violation | 5 | 5 | 4 |
| Overall Study | Withdrawal by Subject | 31 | 17 | 28 |
Baseline characteristics
| Characteristic | Fingolimod 1.25 mg | Fingolimod 0.5 mg | Placebo | Total |
|---|---|---|---|---|
| Age Continuous | 37.4 years STANDARD_DEVIATION 8.91 | 36.6 years STANDARD_DEVIATION 8.77 | 37.2 years STANDARD_DEVIATION 8.6 | 37.1 years STANDARD_DEVIATION 8.76 |
| Age, Customized 18 -30 | 107 participants | 120 participants | 97 participants | 324 participants |
| Age, Customized <18 years | 1 participants | 0 participants | 0 participants | 1 participants |
| Age, Customized 31-40 | 147 participants | 162 participants | 165 participants | 474 participants |
| Age, Customized 41-55 | 174 participants | 143 participants | 156 participants | 473 participants |
| Duration of multiple sclerosis since first symptoms | 8.4 Years STANDARD_DEVIATION 6.86 | 8.0 Years STANDARD_DEVIATION 6.6 | 8.1 Years STANDARD_DEVIATION 6.35 | 8.2 Years STANDARD_DEVIATION 6.6 |
| Expanded Disability Status Scale (EDSS) | 2.41 Units on a scale STANDARD_DEVIATION 1.36 | 2.30 Units on a scale STANDARD_DEVIATION 1.29 | 2.49 Units on a scale STANDARD_DEVIATION 1.29 | 2.40 Units on a scale STANDARD_DEVIATION 1.32 |
| Number of relapses in last 2 years | 1.5 relapses STANDARD_DEVIATION 0.81 | 1.5 relapses STANDARD_DEVIATION 0.76 | 1.4 relapses STANDARD_DEVIATION 0.73 | 1.5 relapses STANDARD_DEVIATION 0.77 |
| Sex: Female, Male Female | 295 Participants | 296 Participants | 298 Participants | 889 Participants |
| Sex: Female, Male Male | 134 Participants | 129 Participants | 120 Participants | 383 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 346 / 429 | 355 / 425 | 323 / 418 |
| serious Total, serious adverse events | 51 / 429 | 43 / 425 | 56 / 418 |
Outcome results
Primary
Estimated Annualized Aggregate Relapse Rate (ARR)
The ARR is defined as the number of confirmed relapses in a year. A relapse is defined as the appearance of a new or worsening of a previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding relapse. The abnormality must be present for at least 24 hours and occur in the absence of fever or infection. The annualized ARR for each treatment group was the mean of the annualized ARRs for all patients in the group calculated as the total number of confirmed relapses divided by the total number of days on study, multiplied by 365.25.
Time frame: Baseline to end of study (Month 24)
Population: This analysis was conducted using the Intent-to-treat (ITT) population which includes all patients who were randomized and received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fingolimod 1.25 mg | Estimated Annualized Aggregate Relapse Rate (ARR) | 0.16 Relapses per year |
| Fingolimod 0.5 mg | Estimated Annualized Aggregate Relapse Rate (ARR) | 0.18 Relapses per year |
| Placebo | Estimated Annualized Aggregate Relapse Rate (ARR) | 0.40 Relapses per year |
Secondary
Number of New or Newly Enlarged T2 Lesions at Month 24 in Comparison With Baseline
The number of new or newly enlarged T2 lesions at Month 24 in comparison to baseline was assessed with T2-weighted magnetic resonance image (MRI) scans. A T2-weighted MRI scan utilizes particular values of the echo time (TE) and the repetition time (TR) parameters of image acquisition. Inflammation and tissue damage are seen as bright areas in T2 images and are often referred to as T2 lesions. T2-weighted MRI scans are a sensitive way to evaluate the brain for demyelinating diseases, such as multiple sclerosis.
Time frame: Baseline to end of study (Month 24)
Population: Intent-to-treat population (ITT): All patients who were randomized and received at least one dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fingolimod 1.25 mg | Number of New or Newly Enlarged T2 Lesions at Month 24 in Comparison With Baseline | 2.5 T2 lesions | Standard Deviation 5.52 |
| Fingolimod 0.5 mg | Number of New or Newly Enlarged T2 Lesions at Month 24 in Comparison With Baseline | 2.5 T2 lesions | Standard Deviation 7.19 |
| Placebo | Number of New or Newly Enlarged T2 Lesions at Month 24 in Comparison With Baseline | 9.8 T2 lesions | Standard Deviation 13.17 |
Secondary
Percentage of Patients Free of Disability Progression at Month 24 Assessed With the Expanded Disability Status Scale (EDSS)
EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) is calculated. Disability progression was determined by the following: One point increase from baseline in patients with baseline EDSS score from 0 to 5.0; or half a point increase in patients with baseline EDSS score of 5.5 or above. A 3-month confirmed disability progression required onset EDSS, 3-month confirming EDSS, and all EDSS in between to meet the disability progression criteria. Percent of free of disability progression was calculated using the Kaplan Meier method.
Time frame: Baseline to end of study (Month 24)
Population: Intent-to-treat population (ITT): All patients who were randomized and received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Fingolimod 1.25 mg | Percentage of Patients Free of Disability Progression at Month 24 Assessed With the Expanded Disability Status Scale (EDSS) | 83.4 Percentage of participants | 95% Confidence Interval 1.87 |
| Fingolimod 0.5 mg | Percentage of Patients Free of Disability Progression at Month 24 Assessed With the Expanded Disability Status Scale (EDSS) | 82.3 Percentage of participants | 95% Confidence Interval 1.89 |
| Placebo | Percentage of Patients Free of Disability Progression at Month 24 Assessed With the Expanded Disability Status Scale (EDSS) | 75.9 Percentage of participants | 95% Confidence Interval 2.17 |