Relapsing Remitting Multiple Sclerosis
Conditions
Keywords
Multiple Sclerosis, Relapsing Remitting Multiple Sclerosis, Fingolimod, Early multiple sclerosis, Naive patients
Brief summary
This study assessed the efficacy of fingolimod in patients with short duration relapsing-remitting multiple sclerosis who had not been previously treated with disease-modifying therapies (DMTs), versus patients with the same disease duration who had previously received first-line DMTs.
Interventions
Hard gelatin capsules containing 0.5 mg of fingolimod.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Patients diagnosed with multiple sclerosis, according to the 2010 revised McDonald criteria, with a relapsing-remitting course, and with at least 9 T2 lesions consistent with the disease, with disease duration greater than or equal to one year and less than or equal to five years. * Patients who have had at least two relapses in the past two years and an Expanded Disability Status Scale score between 0 and 3.5, inclusive. Patients * Treatment naïve: patients who have never been treated with a Disease Modifying Therapy or * Previously treated with a first-line Disease Modifying Therapy
Exclusion criteria
* Patients who have received treatment with: Fingolimod at any time (e.g. participation in a fingolimod clinical trial), Immunosuppressant drugs such as azathioprine or methotrexate at any time; Immunoglobulins in the past 6 months. Monoclonal antibodies including natalizumab, Cladribine, cyclophosphamide or mitoxantrone, at any time. \- Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annual Relapse Rate (ARR) | 12 months | ARR = 365 days \* number of relapses / total days taking the study medication. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Expanded Disability Status Scale (EDSS) Score | baseline, 12 months | The EDSS is an ordinal clinical rating scale ranging from a total score of 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments. A negative change from baseline indicates improvement. |
| Change From Baseline in Cerebral Volume | baseline, 12 months | Cerebral volume was assessed by magnetic resonance imaging (MRI). A negative change from baseline indicates improvement. |
| Time to First Relapse | first day of treatment to the first day of a new neurological symptom or worsening of an existing one, up to 12 months | Time to first relapse was defined as the time from the first day of treatment to the first day of a new neurological symptom or worsening of an existing one. |
| Percentage of Relapse-free Participants | 12 months | Relapse-free participants were defined as participants who experienced no new neurological symptom or worsening of an existing one (relapses) during the 12-month treatment period with 0.5 mg fingolimod. |
| Mean Number of T2 Active Lesions | 12 months | The mean number of new or enlarged T2 active lesions was assessed by MRI. |
| Percentage of Participants With Mild, Moderate or Severe Relapse | 12 months | The investigator classified a relapse as moderate-severe if oral or intravenous (IV) treatment (according to the local clinical practice) with steroids and/or hospitalization was needed. If neither oral nor IV treatment with steroids nor hospitalization was needed, the relapse was considered as mild. |
Countries
Australia, Spain
Participant flow
Pre-assignment details
This was an open-label, non-randomized, parallel group study.
Participants by arm
| Arm | Count |
|---|---|
| Naive or de Novo Participants Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months. | 185 |
| Previously Treated With First-line DMTs Participants Participants received 0.5 mg FTY720 (fingolimod) orally once daily for 12 months. | 135 |
| Total | 320 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Abnormal laboratory value | 2 | 2 |
| Overall Study | Abnormal result from test procedure | 1 | 1 |
| Overall Study | Administrative problems | 1 | 0 |
| Overall Study | Adverse Event | 4 | 1 |
| Overall Study | Lack of Efficacy | 5 | 3 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Protocol Violation | 1 | 3 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Naive or de Novo Participants | Previously Treated With First-line DMTs Participants | Total |
|---|---|---|---|
| Age, Continuous | 33.1 Years STANDARD_DEVIATION 8.08 | 34.0 Years STANDARD_DEVIATION 7.44 | 33.5 Years STANDARD_DEVIATION 7.81 |
| Sex: Female, Male Female | 137 Participants | 88 Participants | 225 Participants |
| Sex: Female, Male Male | 48 Participants | 47 Participants | 95 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 | 143 / 200 | 114 / 147 | 257 / 347 |
| serious Total, serious adverse events | 11 / 200 | 4 / 147 | 15 / 347 |
Outcome results
Primary
Annual Relapse Rate (ARR)
ARR = 365 days \* number of relapses / total days taking the study medication.
Time frame: 12 months
Population: The ITT population was analyzed. The ITT consisted of all participants included in the safety population who met the inclusion/exclusion criteria and had at least one primary endpoint (ARR) measurement recorded.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naive or de Novo Participants | Annual Relapse Rate (ARR) | 0.290 Relapses per year | Standard Deviation 0.7399 |
| Previously Treated With First-line DMTs Participants | Annual Relapse Rate (ARR) | 0.354 Relapses per year | Standard Deviation 0.8547 |
p-value: 0.3118Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline in Cerebral Volume
Cerebral volume was assessed by magnetic resonance imaging (MRI). A negative change from baseline indicates improvement.
Time frame: baseline, 12 months
Population: Participants from the ITT population with both baseline and 12 month values were analyzed. The ITT consisted of all participants included in the safety population who met the inclusion/exclusion criteria and had at least one primary endpoint (ARR) measurement recorded.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Naive or de Novo Participants | Change From Baseline in Cerebral Volume | -0.595 Percent change |
| Previously Treated With First-line DMTs Participants | Change From Baseline in Cerebral Volume | -0.387 Percent change |
Secondary
Change From Baseline in Expanded Disability Status Scale (EDSS) Score
The EDSS is an ordinal clinical rating scale ranging from a total score of 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments. A negative change from baseline indicates improvement.
Time frame: baseline, 12 months
Population: Participants from the ITT population with both baseline and 12 month values were analyzed. The ITT consisted of all participants included in the safety population who met the inclusion/exclusion criteria and had at least one primary endpoint (ARR) measurement recorded.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naive or de Novo Participants | Change From Baseline in Expanded Disability Status Scale (EDSS) Score | 0.000 score on a scale | Standard Deviation 0.804 |
| Previously Treated With First-line DMTs Participants | Change From Baseline in Expanded Disability Status Scale (EDSS) Score | -0.077 score on a scale | Standard Deviation 0.7911 |
Secondary
Mean Number of T2 Active Lesions
The mean number of new or enlarged T2 active lesions was assessed by MRI.
Time frame: 12 months
Population: Participants from the ITT population with 12 month T2 lesion numbers were analyzed. The ITT consisted of all participants included in the safety population who met the inclusion/exclusion criteria and had at least one primary endpoint (ARR) measurement recorded.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Naive or de Novo Participants | Mean Number of T2 Active Lesions | 2.0 T2 lesions | Standard Deviation 3.36 |
| Previously Treated With First-line DMTs Participants | Mean Number of T2 Active Lesions | 1.6 T2 lesions | Standard Deviation 2.72 |
Secondary
Percentage of Participants With Mild, Moderate or Severe Relapse
The investigator classified a relapse as moderate-severe if oral or intravenous (IV) treatment (according to the local clinical practice) with steroids and/or hospitalization was needed. If neither oral nor IV treatment with steroids nor hospitalization was needed, the relapse was considered as mild.
Time frame: 12 months
Population: Only participants from the ITT population with severity values were analyzed. The ITT consisted of all participants included in the safety population who met the inclusion/exclusion criteria and had at least one primary endpoint (ARR) measurement recorded.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Naive or de Novo Participants | Percentage of Participants With Mild, Moderate or Severe Relapse | Mild | 42.55 Percentage of participants |
| Naive or de Novo Participants | Percentage of Participants With Mild, Moderate or Severe Relapse | Moderate | 57.45 Percentage of participants |
| Naive or de Novo Participants | Percentage of Participants With Mild, Moderate or Severe Relapse | Severe | 0.00 Percentage of participants |
| Previously Treated With First-line DMTs Participants | Percentage of Participants With Mild, Moderate or Severe Relapse | Mild | 38.46 Percentage of participants |
| Previously Treated With First-line DMTs Participants | Percentage of Participants With Mild, Moderate or Severe Relapse | Moderate | 56.41 Percentage of participants |
| Previously Treated With First-line DMTs Participants | Percentage of Participants With Mild, Moderate or Severe Relapse | Severe | 5.13 Percentage of participants |
Secondary
Percentage of Relapse-free Participants
Relapse-free participants were defined as participants who experienced no new neurological symptom or worsening of an existing one (relapses) during the 12-month treatment period with 0.5 mg fingolimod.
Time frame: 12 months
Population: The ITT population was analyzed. The ITT consisted of all participants included in the safety population who met the inclusion/exclusion criteria and had at least one primary endpoint (ARR) measurement recorded.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Naive or de Novo Participants | Percentage of Relapse-free Participants | 71.89 Percent |
| Previously Treated With First-line DMTs Participants | Percentage of Relapse-free Participants | 66.67 Percent |
Secondary
Time to First Relapse
Time to first relapse was defined as the time from the first day of treatment to the first day of a new neurological symptom or worsening of an existing one.
Time frame: first day of treatment to the first day of a new neurological symptom or worsening of an existing one, up to 12 months
Population: The ITT population was analyzed. The ITT consisted of all participants included in the safety population who met the inclusion/exclusion criteria and had at least one primary endpoint (ARR) measurement recorded.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Naive or de Novo Participants | Time to First Relapse | NA months |
| Previously Treated With First-line DMTs Participants | Time to First Relapse | NA months |