Table 1.
Study designs of the pivotal phase III and IV trials of daily oral fingolimod in patients with MS
| Study name and identifier | Design | Duration | Patients | Intervention/s | Brain volume assessment |
|---|---|---|---|---|---|
| RMS studies | |||||
| FREEDOMS NCT00289978 [20] |
Multicenter, phase III, randomized, double-blind, placebo-controlled, parallel-group | 2 years | Aged 18–55 years; RMS according to 2005 revised McDonald criteria; ≥1 confirmed relapses during the preceding year (or ≥2 during the previous 2 years); EDSS score of 0.0–5.5; treatment-naïve or previously treated; no relapse or steroid treatment within 30 days of randomization (N = 1272) | Fingolimod 1.25 mg (n = 429) Fingolimod 0.5 mg (n = 425) Placebo (n = 418) |
MRI scan at screening, 6, 12, and 24 months; PBVC evaluated with SIENA |
| FREEDOMS II NCT00355134 [21] |
Multicenter, phase III, randomized, double-blind, placebo-controlled, double-dummy, parallel-group | 2 years | Aged 18–55 years; RMS according to 2005 revised McDonald criteria; ≥1 confirmed relapses during the preceding year (or ≥2 during the previous 2 years); EDSS score of 0.0–5.5; treatment-naïve or previously treated; no relapse or steroid treatment within 30 days of randomization (N = 1083) | Fingolimod 1.25 mg (n = 370) Fingolimod 0.5 mg (n = 358) Placebo (n = 355) |
MRI scan at screening, 6, 12, and 24 months; PBVC evaluated with SIENA |
| TRANSFORMS NCT00340834 [22] |
Multicenter, phase III, randomized, double-blind, active-controlled, double-dummy, parallel-group | 1 year | Aged 18–55 years; RMS according to 2005 revised McDonald criteria; ≥1 confirmed relapses during the preceding year (or ≥2 during the previous 2 years); EDSS score of 0.0–5.5; treatment-naïve or previously treated with IFNβ or GA; no relapse or steroid treatment within 30 days of randomization (N = 1292) | Fingolimod 1.25 mg (n = 426) Fingolimod 0.5 mg (n = 431) IFNβ-1a IM 30 μg/week (n = 435) |
MRI scan at screening and 12 months; PBVC evaluated with SIENA |
| FREEDOMS extension NCT00662649 [27] |
Dose-blinded, parallel-group extension | 2 years | Completed FREEDOMS; did not discontinue study owing to an AE; did not experience onset of chronic immune system disease requiring immunosuppressive treatment (N = 920) |
Continuous
Fingolimod 1.25 mg (n = 289) Fingolimod 0.5 mg (n = 331) Switch Fingolimod 1.25 mg (n = 145) Fingolimod 0.5 mg (n = 155) |
MRI scan every 12 months; PBVC evaluated with SIENA |
| FREEDOMS II extension [29, 72] | Randomized, dose-blinded, then open-label extension | 2 years | Completed FREEDOMS II (N = 632) |
Continuous
Fingolimod 1.25 mg (n = 203) Fingolimod 0.5 mg (n = 217) Switch Fingolimod 1.25 mg (n = 105) Fingolimod 0.5 mg (n = 107) |
MRI scan at baseline, month 12, month 24, and EOS; PBVC evaluated with SIENA |
| TRANSFORMS extension NCT00340834 [28, 36] |
Randomized, dose-blinded, double-blinded, then open-label extension | 2 years, then up to 4.5 years | Completed TRANSFORMS (N = 1027) |
Continuous
Fingolimod 1.25 mg (n = 330) Fingolimod 0.5 mg (n = 356) Switch Fingolimod 1.25 mg (n = 174) Fingolimod 0.5 mg (n = 167) |
MRI scan at screening, month 12, and month 24, at study discontinuation and at a 3-month follow-up visit; PBVC evaluated with SIENA |
| LONGTERMS NCT01281657 [30, 34, 73] |
Single-arm, open-label, long-term follow-up extension | Up to 7 years | Completed phase II, III and IIIb trials or extension studies (N = 2355) |
Continuous
Fingolimod 0.5 mg (n = 783) Switch Placebo–fingolimod 0.5 mg (n = 773) |
MRI scan at screening and at months 6, 12, 24, 36, 48, 60, and 72; PBVC evaluated with SIENA |
| PPMS studies | |||||
| INFORMS NCT00731692 [31] |
Multicenter, phase III, randomized, double-blind, placebo-controlled | 3–5 years | Aged 25–65 years old; PPMS according to 2005 revised McDonald criteria; at least 1 year of disease progression; two or more of the following: positive brain MRI; positive spinal cord MRI; positive cerebrospinal fluid; EDSS score of 3.5–5.6; increase in EDSS score of ≥0.5 points in the past 2 years (N = 970) |
Cohort 1
Fingolimod 1.25 mg (n = 147) Placebo (n = 133) Cohort 2 Fingolimod 0.5 mg (n = 336) Placebo (n = 354) |
MRI scan at screening and every 12 months; PBVC evaluated with SIENA |
AE adverse event, EDSS Expanded Disability Status Scale, EOS end of study, GA glatiramer acetate, IFNβ-1a interferon beta-1a, IM intramuscular, MRI magnetic resonance imaging, MS multiple sclerosis, PBVC percentage brain volume change, PPMS primary progressive multiple sclerosis, RMS relapsing multiple sclerosis, SIENA Structural Image Evaluation, using Normalization, of Atrophy