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 II Multicenter, randomized, placebo-controlled, double-blind, parallel-group	Relapsing MS n = 179	Placebo Teriflunomide 7 mg Teriflunomide 14 mg	36 weeks	Primary: CUALs per MRI Secondary: 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 II Multicenter, 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 II Multicenter randomized, 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 events Secondary: 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 glatiramer acetate in patients with MS (NCT00811395)	Phase II Multicenter randomized, placebo-controlled, double-blind, parallel-group	Relapsing MS with completion of phase II IFN-β or GA add-on studies n = 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 events Secondary: ARR, disability progression, MRI outcomes	Pending
Long-term safety and efficacy of teriflunomide (HMR1726) in MS with relapses (NCT00228163)	Phase II Multicenter, randomized, open-label, parallel-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 events Secondary: ARR, disability accumulation (EDSS, MSFC), MRI outcomes, quality of life, fatigue	Recruitment complete, active. Interim results: favorable safety 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 multiple sclerosis on teriflunomide (TERIVA) (NCT01403376)	Phase II Multicenter, 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 IFN-β + 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

Abbreviations: MS, multiple sclerosis; MRI, magnetic resonance imaging; CUAL, combined unique active lesions; IFN-β, interferon-beta; ARR, annualized relapse rate; Rx, treatment; T₁-Gad, gadolinium-enhancing lesions on T₁-weighted sequence on MRI; GA, glatiramer acetate; EDSS, expanded disability status scale; MSFC, multiple sclerosis functional composite.