Table 1.

Clinical program of fitusiran.

Study (NCT number)	Number and type of participants (N)	Dosing schedule	Key study endpoints	Status
Phase I, Part A [32] (NCT02035605)Timeframe: through day 56 (SAD phase)	N = 4 healthy participants	Fitusiran 0.03 mg/kg SC once	Primary:Safety and tolerabilitySecondary:PharmacokineticsPharmacodynamics	Completed
Phase I, Part B [32] (NCT02035605)Timeframe: through day 70 (MAD phase)	N = 12 people with moderate/severe hemophilia A/B with previous prophylaxis	Fitusiran 0.015, 0.045 or 0.075 mg/kg SC QW x 3
Phase I, Part C [32] (NCT02035605)Timeframe: through day 112 (MD phase)a	N = 18 people with moderate/severe hemophilia A/B with previous prophylaxisa	Fitusiran 0.225, 0.45, 0.9 or 1.8 mg/kg or 80 mg SC QM x 3
Phase I, Part D [39] (NCT02035605)Timeframe: through day 112 (MD phase in patients with inhibitors)	N = 17 people with moderate/severe hemophilia A/B, with inhibitors	Fitusiran 50 or 80 mg SC QM ×3
Phase II open-label extension [46,55] (NCT02554773)	N = 34 people with moderate/severe hemophilia A/B, with or without inhibitors who tolerated fitusiran in Phase I (Parts B, C, and D)	Fitusiran 50 or 80 mg SC QM, then following the revised protocol as of December 2020	Primary:Long-term safety and tolerabilitySecondary:ABRAssessment of concomitantly administered FVIII, FIX, or BPA for bleeding episodesHRQoLPharmacokineticsPharmacodynamicsPlasma AT levelsPlasma thrombin generation	Active, not recruiting
Phase III ATLAS-A/B [51,57] (NCT03417245)	N = 120 people with severe hemophilia A/B without inhibitors previously treated on-demand	Fitusiran 80 mg SC QM prophylaxis (n = 80)On-demand factor concentrates (n = 40)Duration: 9 mo	Primary:ABRSecondary:Spontaneous ABRJoint ABRHRQoLTEAEs and SAEs	Completed
Phase III ATLAS-INH [50,56] (NCT03417102)	N = 57 people with severe hemophilia A/B with inhibitors previously treated on demand	Fitusiran 80 mg SC QM prophylaxis (n = 38)On-demand BPAs (n = 19)Duration: 9 mo	Primary:ABRSecondary:Spontaneous ABRJoint ABRHRQoLTEAEs and SAEs	Completed
Phase III ATLAS-PPX [49,58] (NCT03549871)	N = 80 people with severe hemophilia A/B previously receiving factor or BPA prophylaxis	Fitusiran 80 mg SC QM for 7 mo	Primary:ABRSecondary:Spontaneous ABRJoint ABRHRQoLTEAEs (19 mo [including up to 6 mo of AT follow-up])	Completed
Phase III ATLAS- open-label extension [48] (NCT03754790)	Actual enrollment: N = 355 people with hemophilia with or without inhibitory antibodies (FVIII, FIX)	Fitusiran 80 mg SC QM for 48 months then following the revised regimen	Primary:Safety and tolerabilitySecondary:ABRSpontaneous ABRJoint ABRHRQoL	Active, not recruiting
Phase III ATLAS-PEDS [47] (NCT03974113)	Estimated enrollment: N = 32 male pediatric participants (aged 1 to <12 y) with severe hemophilia A/B with inhibitors	Fitusiran SC at regular intervals as per study protocol	Primary:Plasma AT activity levels at the end of the efficacy period (approximately 160 wk)Secondary:AEs (160 wk)Fitusiran plasma concentrations (days 1 and 85)	Active, recruiting
Phase III ATLAS-NEO [53] (NCT05662319)	Estimated enrollment: N = 75 male adult and adolescent ≥12 y old with hemophilia A/B with or without inhibitory antibodies (FVIII, FIX)	In SoC period, on-demand or prophylactic treatment with CFCs or BPAs for 6 mo. In fitusiran treatment period, SC fitusiran prophylaxis Q2M or QM for 36 mo	Primary:ABR in the fitusiran efficacy periodSecondary:ABR while on fitusiran prophylaxis and ABR while on SoC prophylaxisABR while on fitusiran prophylaxis and ABR while on on-demand SoCSpontaneous ABR in the fitusiran efficacy period and the SoC periodJoint ABR in the fitusiran efficacy period and the SoC periodHaem-A-QoL in the fitusiran efficacy period and the SoC periodAE	Active, recruiting

ABR, annualized bleeding rate; AE, adverse event; AT, antithrombin; BPA, bypassing agent; CFC, clotting factor concentrate; FIX, factor IX; FVIII, factor VIII; FX, factor X; Haem-A-QoL, The Haemophilia Quality of Life Questionnaire for Adults; HRQoL, health-related quality of life; MAD, multiple-ascending dose; MD, multiple dose; QM, once-monthly; Q2M, once every other month; QW, once-weekly; SAD, single-ascending dose; SAE, serious adverse event; SoC, standard of care; TEAE, treatment emergent adverse event.

^aUntil AT activity returns to ≥80% of levels measured at screening.