Clinical data from completed phase 2 trials with FXI and FXII inhibitors
| Agent . | Registry number (name) . | Clinical trial phase and indication . | No. of patients . | Comparator . | Efficacy outcome . | Safety outcome . | Remarks . |
|---|---|---|---|---|---|---|---|
| IONIS FXI-Rx (ISIS 416858) | NCT01713361 | Phase 2 VTE prevention in patients undergoing TKA48 | 315 | SC enoxaparin 40 mg OD | Composite of asymptomatic DVT (via bilateral venography) and symptomatic VTE, fatal PE, and unexplained death | Major bleeding or CRNMB | IONIS FXI-Rx 200 mg noninferior efficacy, 300 mg superior efficacy, comparable safety |
| NCT02553889 | Phase 2 Patients with ESRD on hemodialysis50 | 49 | Placebo | PK | Safety and tolerability; frequency and severity of adverse events | PK in patients with ESRD consistent with previous reports in healthy volunteers Less category 3 or 4 clots in the air traps and dialysis membranes | |
| Abelacimab (MAA868) | EudraCT 2019-003756-37 (ANT-005 TKA) | Phase 2 VTE prevention in patients undergoing TKA53 | 412 | SC enoxaparin 40 mg OD | Confirmed VTE (via ipsilateral venography) and symptomatic VTE | Major bleeding or CRNMB | 30 mg abelacimab noninferior efficacy, 75 mg and 150 mg superior efficacy, comparable safety |
| Osocimab (BAY 1213790) | NCT03276143 (FOXTROT) | Phase 2 VTE prevention in patients undergoing TKA57 | 813 | SC enoxaparin 40 mg OD or oral apixaban 2.5 mg BID | Composite of asymptomatic DVT (via bilateral venography) and symptomatic VTE, fatal PE, and unexplained death | Major bleeding or CRNMB | Postoperative osocimab 0.6-1.2 mg/kg noninferior to enoxaparin, preoperative osocimab 1.8 mg/kg superior, but ↑ bleeding |
| Xisomab (AB023) | NCT03612856 | Phase 2 Patients with ESRD on hemodialysis61 | 24 | Placebo | Hemodialysis efficiency as measured by frequency of clotting on the dialysis filters and circuit and levels of potassium and blood urea nitrogen | Treatment-related AEs, bleeding | Xisomab well tolerated, less occlusive events |
| Garadacimab (CSL312) | NCT03712228 | Phase 2 Prevention of attacks in HAE-C1-INH36 | 32 | Placebo | Time-normalized number of HAE-C1-INH attacks during treatment period | AEs and serious AEs, anaphylaxis, thromboembolic events, and bleeding events | Garadacimab significantly reduced the number of monthly attacks vs placebo and was well tolerated during the study |
| Milvexian (BMS-986177/JNJ-70033093) | NCT03891524 (AXIOMATIC-TKR) | Phase 2 VTE prevention in patients undergoing TKA66 | 1242 | SC enoxaparin 40 mg OD | Confirmed VTE (via ipsilateral venography) and symptomatic VTE | Major bleeding or CRNMB | Met proof-of-efficacy criteria; VTE incidence 12% significantly lower than the prespecified benchmark of 30% (1-sided P < .001) |
| Asundexian (BAY 2433334) | NCT04218266 (PACIFIC-AF) | Phase 2 Stroke prevention in AF68 | 753 | Apixaban 5 mg BID | NA | Major bleeding or CRNMB | Lower bleeding rates with asundexian 20 mg and 50 mg OD vs apixaban |
| Agent . | Registry number (name) . | Clinical trial phase and indication . | No. of patients . | Comparator . | Efficacy outcome . | Safety outcome . | Remarks . |
|---|---|---|---|---|---|---|---|
| IONIS FXI-Rx (ISIS 416858) | NCT01713361 | Phase 2 VTE prevention in patients undergoing TKA48 | 315 | SC enoxaparin 40 mg OD | Composite of asymptomatic DVT (via bilateral venography) and symptomatic VTE, fatal PE, and unexplained death | Major bleeding or CRNMB | IONIS FXI-Rx 200 mg noninferior efficacy, 300 mg superior efficacy, comparable safety |
| NCT02553889 | Phase 2 Patients with ESRD on hemodialysis50 | 49 | Placebo | PK | Safety and tolerability; frequency and severity of adverse events | PK in patients with ESRD consistent with previous reports in healthy volunteers Less category 3 or 4 clots in the air traps and dialysis membranes | |
| Abelacimab (MAA868) | EudraCT 2019-003756-37 (ANT-005 TKA) | Phase 2 VTE prevention in patients undergoing TKA53 | 412 | SC enoxaparin 40 mg OD | Confirmed VTE (via ipsilateral venography) and symptomatic VTE | Major bleeding or CRNMB | 30 mg abelacimab noninferior efficacy, 75 mg and 150 mg superior efficacy, comparable safety |
| Osocimab (BAY 1213790) | NCT03276143 (FOXTROT) | Phase 2 VTE prevention in patients undergoing TKA57 | 813 | SC enoxaparin 40 mg OD or oral apixaban 2.5 mg BID | Composite of asymptomatic DVT (via bilateral venography) and symptomatic VTE, fatal PE, and unexplained death | Major bleeding or CRNMB | Postoperative osocimab 0.6-1.2 mg/kg noninferior to enoxaparin, preoperative osocimab 1.8 mg/kg superior, but ↑ bleeding |
| Xisomab (AB023) | NCT03612856 | Phase 2 Patients with ESRD on hemodialysis61 | 24 | Placebo | Hemodialysis efficiency as measured by frequency of clotting on the dialysis filters and circuit and levels of potassium and blood urea nitrogen | Treatment-related AEs, bleeding | Xisomab well tolerated, less occlusive events |
| Garadacimab (CSL312) | NCT03712228 | Phase 2 Prevention of attacks in HAE-C1-INH36 | 32 | Placebo | Time-normalized number of HAE-C1-INH attacks during treatment period | AEs and serious AEs, anaphylaxis, thromboembolic events, and bleeding events | Garadacimab significantly reduced the number of monthly attacks vs placebo and was well tolerated during the study |
| Milvexian (BMS-986177/JNJ-70033093) | NCT03891524 (AXIOMATIC-TKR) | Phase 2 VTE prevention in patients undergoing TKA66 | 1242 | SC enoxaparin 40 mg OD | Confirmed VTE (via ipsilateral venography) and symptomatic VTE | Major bleeding or CRNMB | Met proof-of-efficacy criteria; VTE incidence 12% significantly lower than the prespecified benchmark of 30% (1-sided P < .001) |
| Asundexian (BAY 2433334) | NCT04218266 (PACIFIC-AF) | Phase 2 Stroke prevention in AF68 | 753 | Apixaban 5 mg BID | NA | Major bleeding or CRNMB | Lower bleeding rates with asundexian 20 mg and 50 mg OD vs apixaban |
AEs, adverse events; BID, twice daily; CRNMB, clinically relevant nonmajor bleeding; DVT, deep venous thrombosis; HAE-C1-INH, C1-esterase inhibitor-deficient hereditary angioedema; NA, not available; OD, once daily; PE, pulmonary emboli; PK, pharmacokinetics.