Trials of drugs targeting FXI(a) for patients undergoing TKA
| Clinical trial (drug) . | Dosing . | Primary efficacy end point . | Primary safety end point . | Incidence of venous thrombosis . | Incidence of bleeding . |
|---|---|---|---|---|---|
| FXI-ASO TKA (Ionis FXI Rx) | 9 subcutaneous doses starting 36 days before op. Last dose 3 days after op | VTE by bilateral venography 8-12 d after op or symptomatic VTE | Major or clinically relevant nonmajor bleeding out to 100 d after op | Ionis FXIRx 200 mg (27%)∗, Ionis FXIRx 300 mg (4%)† Enoxaparin (30%) | Major or CRNM bleeding: Ionis FXIRx 200 mg (3%) and 300 mg (3%) Enoxaparin (8%) |
| FOXTROT (osocimab) | Single IV dose the day after surgery or just before surgery | VTE by bilateral venography 10-13 d after op or symptomatic VTE | Major or clinically relevant nonmajor bleeding out to 10-13 d after op | Post-op osocimab (mg/kg): 0.3 (23.7%), 0.6 (15.7%)∗, 1.2 (16.5)∗, 1.8 (17.9%)∗, Pre-op osocimab (mg/kg): 0.3 (29.9%) and 1.8 (11.3%)† Enoxaparin (26.3%) Apixaban (14.5%) | Major or CRNM bleeding: Osocimab after op (0%-3%) Osocimab before op (1.9%-5.9%) Enoxaparin (5.9%) Apixaban (2%) |
| ANT-005 TKA (abelacimab) | Single IV dose 4-8 h after op | VTE by venography of involved leg 8-12 d after op or symptomatic VTE | Major or clinically relevant nonmajor bleeding out to 30 d after op | Abelacimab: 30 mg (13%)∗, 75 mg (5%)†, and 150 mg (4%)† Enoxaparin (22%) | Major or CRNM bleeding: Abelacimab 30 mg (2%), 75 mg (2%), and 150 mg (0%) Enoxaparin (0%) |
| AXIOMATIC-TKR (milvexian) | Once-daily or BID oral dosing starting 12-24 h after op, for 10-14 d | VTE by venography of involved leg 10-14 d after op, symptomatic VTE or death | Major, clinically relevant nonmajor, and minimal bleeding out to 6 wks after op | Milvexian BID: 25 mg (21%), 50 mg (11%)‡, 100 mg (9%)‡, and 200 mg (8%)‡, Milvexian once per day: 25 mg (25%), 50 mg (24%), and 200 mg (7%)‡ Enoxaparin (21%) | Major or CRNM bleeding: Milvexian (1%) and enoxaparin (2%) Any bleeding: Milvexian (4%) and enoxaparin (4%) |
| Clinical trial (drug) . | Dosing . | Primary efficacy end point . | Primary safety end point . | Incidence of venous thrombosis . | Incidence of bleeding . |
|---|---|---|---|---|---|
| FXI-ASO TKA (Ionis FXI Rx) | 9 subcutaneous doses starting 36 days before op. Last dose 3 days after op | VTE by bilateral venography 8-12 d after op or symptomatic VTE | Major or clinically relevant nonmajor bleeding out to 100 d after op | Ionis FXIRx 200 mg (27%)∗, Ionis FXIRx 300 mg (4%)† Enoxaparin (30%) | Major or CRNM bleeding: Ionis FXIRx 200 mg (3%) and 300 mg (3%) Enoxaparin (8%) |
| FOXTROT (osocimab) | Single IV dose the day after surgery or just before surgery | VTE by bilateral venography 10-13 d after op or symptomatic VTE | Major or clinically relevant nonmajor bleeding out to 10-13 d after op | Post-op osocimab (mg/kg): 0.3 (23.7%), 0.6 (15.7%)∗, 1.2 (16.5)∗, 1.8 (17.9%)∗, Pre-op osocimab (mg/kg): 0.3 (29.9%) and 1.8 (11.3%)† Enoxaparin (26.3%) Apixaban (14.5%) | Major or CRNM bleeding: Osocimab after op (0%-3%) Osocimab before op (1.9%-5.9%) Enoxaparin (5.9%) Apixaban (2%) |
| ANT-005 TKA (abelacimab) | Single IV dose 4-8 h after op | VTE by venography of involved leg 8-12 d after op or symptomatic VTE | Major or clinically relevant nonmajor bleeding out to 30 d after op | Abelacimab: 30 mg (13%)∗, 75 mg (5%)†, and 150 mg (4%)† Enoxaparin (22%) | Major or CRNM bleeding: Abelacimab 30 mg (2%), 75 mg (2%), and 150 mg (0%) Enoxaparin (0%) |
| AXIOMATIC-TKR (milvexian) | Once-daily or BID oral dosing starting 12-24 h after op, for 10-14 d | VTE by venography of involved leg 10-14 d after op, symptomatic VTE or death | Major, clinically relevant nonmajor, and minimal bleeding out to 6 wks after op | Milvexian BID: 25 mg (21%), 50 mg (11%)‡, 100 mg (9%)‡, and 200 mg (8%)‡, Milvexian once per day: 25 mg (25%), 50 mg (24%), and 200 mg (7%)‡ Enoxaparin (21%) | Major or CRNM bleeding: Milvexian (1%) and enoxaparin (2%) Any bleeding: Milvexian (4%) and enoxaparin (4%) |