Table 1.
Phase II clinical trials of teriflunomide in multiple sclerosis.
| Clinical trial name (ClinicalTrials.gov identifier) | Study phase/ design | Study participants | Study arms | Treatment period | Primary/key secondary outcomes | Results |
|---|---|---|---|---|---|---|
| Safety and efficacy of teriflunomide in MS with relapses (NCT01487096) |
Phase IIMulticenter, randomized, placebo-controlled, double-blind, parallel group | Relapsing MSn = 179 | - Placebo - Teriflunomide 7 mg - Teriflunomide 14 mg |
36 weeks | Primary: CUALs per MRISecondary: other MRI outcomes, relapse frequency, disability progression, safety and tolerability | - Decrease in CUALs in both Rx groups - Decrease in other MRI outcomes in both Rx groups - Decrease in disability progression in 14 mg Rx group, trend towards a decrease in 7 mg group - Well-tolerated |
| Pilot study of teriflunomide as adjunctive therapy to IFN-β in subjects with MS (NCT00489489) |
Phase IIMulticenter,randomized, placebo-controlled, double-blind, parallel group | Relapsing MS on stable dose of IFN-β (>26 weeks)n = 118 | - IFN-β + placebo - IFN-β + teriflunomide 7 mg - IFN-β + teriflunomide 14 mg |
24 weeks | Primary: number of patients with adverse events, clinically significant abnormalities Secondary: ARR, MRI outcomes |
- Well-tolerated - Reduced number of T1-Gd lesions both Rx groups - T1-Gd lesion volume reduced in 14 mg Rx groups - Trend towards reduced ARR in high-dose Rx group |
| Pilot study of teriflunomide as adjunctive therapy to GA in subjects with MS (NCT00475865) |
Phase IIMulticenterrandomized, placebo-controlled, double-blind, parallel group | Relapsing MS on stable dose of GA (>26 weeks)n = 123 | - GA + placebo - GA + teriflunomide 7 mg - GA + teriflunomide 14 mg |
24 weeks | Primary: number of patients with adverse eventsSecondary: ARR, MRI outcomes, fatigue | - Acceptable safety - Decrease in T1-Gd lesion count in 7 mg Rx group - Decrease in T1-Gd volume in 14 mg Rx group |
| Long-term safety of teriflunomide when added to IFN-β or GA in patients with MS (NCT00811395) |
Phase IIMulticenterrandomized, placebo-controlled, double-blind, parallel group | Relapsing MS with completion of phase II IFN-β or GA add-on studiesn = 182 | - IFN-β + placebo - IFN-β + teriflunomide 7 mg - IFN-β + teriflunomide 14 mg - GA + placebo - GA + teriflunomide 7 mg - GA + teriflunomide 14 mg |
24 weeks | Primary: number of patients with adverse eventsSecondary: ARR, disability progression, MRI outcomes | - Pending |
| Long-term safety and efficacy of teriflunomide (HMR1726) in MS with relapses (NCT00228163) |
Phase IIMulticenter, randomized,open-labelparallel group | Relapsing MS with completion of phase II monotherapy study n = 180 (estimated); n = 147 (interim) |
- Teriflunomide 7 mg daily - Teriflunomide 14 mg daily |
528 weeks | Primary: number of patients with adverse eventsSecondary: ARR, disability accumulation (EDSS, MSFC), MRI outcomes, QOL, fatigue | Interim results: Favorablesafety profile - low annualized relapse rates- minimal disability progression - dose-dependent benefit with high-dose Rx for several MRI outcomes |
| Study to investigate the immune response to influenza vaccine in patients with MS on teriflunomide (TERIVA) (NCT01403376) |
Phase IIMulticenter, multinational, parallel-group | Relapsing MS treated for ≥6 months with: teriflunomide 7 mg or 14 mg, stable dose of IFN-β | - Teriflunomide 7 mg + influenza vaccine - Teriflunomide 14 mg + influenza vaccine - IFNβ + influenza vaccine |
28 days | Primary: proportion of patients who achieved seroprotection to influenza vaccine strains H1N1, H3N2 and B at 28 days postvaccination | - MS patients treated with teriflunomide mounted effective immune responses to the seasonal influenza vaccination - As expected, MS patients in the reference IFN-β group mounted an effective immune response to influenza vaccine - No new safety concerns identified in patients treated with teriflunomide following influenza vaccination |
ARR, annualized relapse rate; CUAL, combined unique active lesions; EDSS, Expanded Disability Status Scale; GA, glatiramer acetate; IFN-β, interferon-beta; MRI, magnetic resonance imaging; MS, multiple sclerosis; MSFC, Multiple Sclerosis Functional Composite; QOL, quality of life; Rx, treatment; T1-Gad, gadolinium-enhancing lesions on T1 weighted sequence on MRI.