Snapshot of PERSIST-2 and PAC-203 clinical trials
| . | PERSIST-235 . | PAC20338 . |
|---|---|---|
| Design | Phase 3/randomized 1:1:1 | Phase 2/randomized 1:1:1 |
| Inclusion criteria | ||
| Disease | Primary, post-ET/PVMF | Primary, post-ET/PVMF |
| Risk | DIPSS INT-1, INT-2, high risk | DIPSS INT-1, INT-2, high risk |
| Prior RX | 1 or 2 JAK-inhibitors | Ruxolitinib |
| Platelet count | ≤100 × 109/L | Any |
| Ruxolitinib (RUX) Intolerance | N/A | RUX<20 mg twice day for ≥ 28 complicated by a requirement for red blood cell transfusion, grade ≥ 3 anemia, thrombocytopenia, hematoma, and/or hemorrhage |
| Ruxolitinib failure | N/A | RUX treatment for ≥ 3 mo with < 10% SVR or < 30% decrease in spleen length or regrowth |
| Key exclusion criteria | ||
| To mitigate bleeding risk | Active bleeding | a) Grade ≥ 2 bleeding events within the previous 3 mo b) Treated with anticoagulation or antiplatelet agents within 14 d prior to starting treatment |
| To mitigate cardiovascular risk | a) Symptomatic/uncontrolled cardiac disease b) NYHA class 3-4 c) MI or unstable angina or CHF 6 mo prior to randomization d) Grade ≥3 cardiac arrythmias e) QTc ≥ 450 ms | a) NYHA class≥2 heart failure b) Grade ≥ 2 cardiac conditions within 6 mo prior to starting treatment c) QTc > 450 ms d) LVEF < 45% |
| Intervention | ||
| Dosing/arms | PAC 400 mg once daily | PAC 100 mg once daily |
| PAC 200 mg twice daily | PAC 100 mg twice daily | |
| BAT (physician choice, symptomatic treatment, observation) | PAC 200 mg twice daily | |
| End points | Co-primary end points | Primary objective: to determine the recommended dose of PAC |
| – SVR 35% and TSS50 at week 24 | Secondary objectives: | |
| a) examine the dose-response relationship for efficacy and safety b) characterize pharmacokinetics and pharmacodynamics of PAC | ||
| SVR35% at week 24 | ||
| Overall | PAC 400 mg daily – 15% | PAC 100 mg once daily – 0% |
| PAC 200 mg twice daily – 22% | PAC 100 mg twice daily – 1.8% | |
| BAT – 3% | PAC 200 mg twice daily – 9.3% | |
| Platelet count <50 × 109/L | PAC 400 mg daily – 18% | PAC 100 mg once daily – 0% |
| PAC 200 mg twice daily–29% | PAC 100 mg twice daily – 0% | |
| BAT – 3% | PAC 200 mg twice daily – 16.7% | |
| TSS50 | ||
| Overall | PAC 400 mg daily – 17% | PAC 100 mg once daily – 7.7% |
| PAC 200 mg twice daily – 32% | PAC 100 mg twice daily – 7.3% | |
| BAT – 14% | PAC 200 mg twice daily – 7.4% | |
| Platelet count <50 × 109/L | PAC 400 mg daily – 16% | PAC 100 mg once daily – 8.7% |
| PAC 200 mg twice daily – 23% | PAC 100 mg twice daily – 0% | |
| BAT – 13% | PAC 200 mg twice daily – 8.3% | |
| Most common TEAEs | ||
| Nonhematologic | ||
| Diarrhea Gr 1 or 2 | PAC 400 mg daily – 67% | PAC 200 mg twice daily – 29.6% |
| PAC 200 mg twice daily – 48% | ||
| BAT – 15% | ||
| Hematologic | ||
| Thrombocytopenia | PAC 400 mg daily – 33% | PAC 200 mg twice daily – 40.7% |
| PAC 200 mg twice daily – 34% | ||
| BAT–23% | ||
| Anemia | PAC 400 mg daily – 33% | PAC 200 mg twice daily – 24.9% |
| PAC 200 mg twice daily – 34% | ||
| BAT – 23% | ||
| TEAE of special interest in patients with platelets ≤ 50 × 109/L 39 | ||
| Cardiac event grade ≥ 3 | PAC 400 mg daily – 13% | PAC 200 mg twice daily – 8% |
| PAC 200 mg twice daily – 9% | ||
| BAT – 19% | ||
| Any bleeding grade ≥ 3 | PAC 400 mg daily – 13% | PAC 200 mg twice daily – 13% |
| PAC 200 mg twice daily – 17% | ||
| BAT – 12% | ||
| . | PERSIST-235 . | PAC20338 . |
|---|---|---|
| Design | Phase 3/randomized 1:1:1 | Phase 2/randomized 1:1:1 |
| Inclusion criteria | ||
| Disease | Primary, post-ET/PVMF | Primary, post-ET/PVMF |
| Risk | DIPSS INT-1, INT-2, high risk | DIPSS INT-1, INT-2, high risk |
| Prior RX | 1 or 2 JAK-inhibitors | Ruxolitinib |
| Platelet count | ≤100 × 109/L | Any |
| Ruxolitinib (RUX) Intolerance | N/A | RUX<20 mg twice day for ≥ 28 complicated by a requirement for red blood cell transfusion, grade ≥ 3 anemia, thrombocytopenia, hematoma, and/or hemorrhage |
| Ruxolitinib failure | N/A | RUX treatment for ≥ 3 mo with < 10% SVR or < 30% decrease in spleen length or regrowth |
| Key exclusion criteria | ||
| To mitigate bleeding risk | Active bleeding | a) Grade ≥ 2 bleeding events within the previous 3 mo b) Treated with anticoagulation or antiplatelet agents within 14 d prior to starting treatment |
| To mitigate cardiovascular risk | a) Symptomatic/uncontrolled cardiac disease b) NYHA class 3-4 c) MI or unstable angina or CHF 6 mo prior to randomization d) Grade ≥3 cardiac arrythmias e) QTc ≥ 450 ms | a) NYHA class≥2 heart failure b) Grade ≥ 2 cardiac conditions within 6 mo prior to starting treatment c) QTc > 450 ms d) LVEF < 45% |
| Intervention | ||
| Dosing/arms | PAC 400 mg once daily | PAC 100 mg once daily |
| PAC 200 mg twice daily | PAC 100 mg twice daily | |
| BAT (physician choice, symptomatic treatment, observation) | PAC 200 mg twice daily | |
| End points | Co-primary end points | Primary objective: to determine the recommended dose of PAC |
| – SVR 35% and TSS50 at week 24 | Secondary objectives: | |
| a) examine the dose-response relationship for efficacy and safety b) characterize pharmacokinetics and pharmacodynamics of PAC | ||
| SVR35% at week 24 | ||
| Overall | PAC 400 mg daily – 15% | PAC 100 mg once daily – 0% |
| PAC 200 mg twice daily – 22% | PAC 100 mg twice daily – 1.8% | |
| BAT – 3% | PAC 200 mg twice daily – 9.3% | |
| Platelet count <50 × 109/L | PAC 400 mg daily – 18% | PAC 100 mg once daily – 0% |
| PAC 200 mg twice daily–29% | PAC 100 mg twice daily – 0% | |
| BAT – 3% | PAC 200 mg twice daily – 16.7% | |
| TSS50 | ||
| Overall | PAC 400 mg daily – 17% | PAC 100 mg once daily – 7.7% |
| PAC 200 mg twice daily – 32% | PAC 100 mg twice daily – 7.3% | |
| BAT – 14% | PAC 200 mg twice daily – 7.4% | |
| Platelet count <50 × 109/L | PAC 400 mg daily – 16% | PAC 100 mg once daily – 8.7% |
| PAC 200 mg twice daily – 23% | PAC 100 mg twice daily – 0% | |
| BAT – 13% | PAC 200 mg twice daily – 8.3% | |
| Most common TEAEs | ||
| Nonhematologic | ||
| Diarrhea Gr 1 or 2 | PAC 400 mg daily – 67% | PAC 200 mg twice daily – 29.6% |
| PAC 200 mg twice daily – 48% | ||
| BAT – 15% | ||
| Hematologic | ||
| Thrombocytopenia | PAC 400 mg daily – 33% | PAC 200 mg twice daily – 40.7% |
| PAC 200 mg twice daily – 34% | ||
| BAT–23% | ||
| Anemia | PAC 400 mg daily – 33% | PAC 200 mg twice daily – 24.9% |
| PAC 200 mg twice daily – 34% | ||
| BAT – 23% | ||
| TEAE of special interest in patients with platelets ≤ 50 × 109/L 39 | ||
| Cardiac event grade ≥ 3 | PAC 400 mg daily – 13% | PAC 200 mg twice daily – 8% |
| PAC 200 mg twice daily – 9% | ||
| BAT – 19% | ||
| Any bleeding grade ≥ 3 | PAC 400 mg daily – 13% | PAC 200 mg twice daily – 13% |
| PAC 200 mg twice daily – 17% | ||
| BAT – 12% | ||
DIPSS, Dynamic International Prognostic Scoring System; ET, essential thrombocythemia; PV, polycythemia vera.