Baseline demographic and clinical characteristics
| Characteristic, median (range), unless indicated . | Single dose . | MAD . | OL . | |||
|---|---|---|---|---|---|---|
| Placebo . | Etavopivat single dose . | Pooled placebo . | Etavopivat once daily for 2 wk . | Etavopivat once daily for 12 wk . | ||
| (n = 2) . | 700 mg (n = 5) . | (n = 4) . | MAD1, 300 mg (n = 8) . | MAD2, 600 mg (n = 8) . | 400 mg (n = 15) . | |
| Age, y | 45 (42-48) | 32 (15-42) | 26.5 (17-36) | 24.0 (19-43) | 29.5 (22-64) | 33.0 (17-55) |
| Male sex, n (%) | 1 (50.0) | 1 (20.0) | 3 (75.0) | 2 (25.0) | 1 (12.5) | 5 (33.3) |
| Genotype, n (%) | ||||||
| HbSS | 2 (100) | 5 (100) | 4 (100) | 7 (87.5) | 6 (75.0) | 13 (86.7) |
| HbSC | 0 | 0 | 0 | 0 | 1 (12.5) | 2 (13.3) |
| HbSβ+ thalassemia | 0 | 0 | 0 | 1 (12.5) | 1 (12.5) | 0 |
| Current HU therapy, n (%) | 2 (100) | 5 (100) | 3 (75.0) | 6 (75.0) | 7 (87.5) | 13 (86.7) |
| Hb, g/dL | 7.2 (6.7-7.7) | 9.7 (7.7-10.4) | 7.6 (7.1-8.0) | 9.1 (6.9-10.1) | 8.9 (7.3-10.2) | 8.7 (7.2-10.1) |
| % HbS | 79.7 (70.2-89.1) | 78.8 (70-86.5) | 84.6 (76.6-92.7) | 83.3 (67.0-92.9) | 80.1 (78.2-87.8) | 80.3 (46.2-92.7) |
| % HbF | 17.4 (7.3-27.5) | 11.4 (5.5-20.5) | 10.0 (4.4-16.6) | 9.8 (3.5-20.1) | 15.3 (5.2-19.2) | 11.5 (1.2-23) |
| Advia MCV, fL∗ | 113.3 (101.6-125.0) | 108.7 (96.5-122.8) | 107.4 (100.1-131.5) | 112.9 (75.0-117.6) | 114.7 (68.5-129.6) | 108.1 (77.1-122.7) |
| ARC, ×109/L† | 178.1 (72.9-283.4) | 205.5 (136.0-366.4) | 238.4 (227.0-360.6) | 274.1 (125.6-329.6) | 226.8 (29.4-366.0) | 219.3 (80.5-511.0) |
| iBIL, mg/dL‡ | 3.8 (2.1-5.4) | 2.3 (1.6-5.1) | 2.8 (2.0-5.0) | 1.7 (0.5-10.5) | 1.3 (0.7-4.5) | 1.3 (0.8-5.2) |
| LDH, U/L | 374.5 (348-401) | 405.0 (308-543) | 352.0 (180-683) | 381.5 (207-699) | 368.5 (251-683) | 367.0 (186-683) |
| % F cells§ | 62.6 (33.3-91.8) | 50.6 (34.4-75.5) | 26.2 (22.3-30.1) | 36.1 (16.4-67.2) | 54.4 (13.3-64.8) | 54.4 (6.1-76.9) |
| Characteristic, median (range), unless indicated . | Single dose . | MAD . | OL . | |||
|---|---|---|---|---|---|---|
| Placebo . | Etavopivat single dose . | Pooled placebo . | Etavopivat once daily for 2 wk . | Etavopivat once daily for 12 wk . | ||
| (n = 2) . | 700 mg (n = 5) . | (n = 4) . | MAD1, 300 mg (n = 8) . | MAD2, 600 mg (n = 8) . | 400 mg (n = 15) . | |
| Age, y | 45 (42-48) | 32 (15-42) | 26.5 (17-36) | 24.0 (19-43) | 29.5 (22-64) | 33.0 (17-55) |
| Male sex, n (%) | 1 (50.0) | 1 (20.0) | 3 (75.0) | 2 (25.0) | 1 (12.5) | 5 (33.3) |
| Genotype, n (%) | ||||||
| HbSS | 2 (100) | 5 (100) | 4 (100) | 7 (87.5) | 6 (75.0) | 13 (86.7) |
| HbSC | 0 | 0 | 0 | 0 | 1 (12.5) | 2 (13.3) |
| HbSβ+ thalassemia | 0 | 0 | 0 | 1 (12.5) | 1 (12.5) | 0 |
| Current HU therapy, n (%) | 2 (100) | 5 (100) | 3 (75.0) | 6 (75.0) | 7 (87.5) | 13 (86.7) |
| Hb, g/dL | 7.2 (6.7-7.7) | 9.7 (7.7-10.4) | 7.6 (7.1-8.0) | 9.1 (6.9-10.1) | 8.9 (7.3-10.2) | 8.7 (7.2-10.1) |
| % HbS | 79.7 (70.2-89.1) | 78.8 (70-86.5) | 84.6 (76.6-92.7) | 83.3 (67.0-92.9) | 80.1 (78.2-87.8) | 80.3 (46.2-92.7) |
| % HbF | 17.4 (7.3-27.5) | 11.4 (5.5-20.5) | 10.0 (4.4-16.6) | 9.8 (3.5-20.1) | 15.3 (5.2-19.2) | 11.5 (1.2-23) |
| Advia MCV, fL∗ | 113.3 (101.6-125.0) | 108.7 (96.5-122.8) | 107.4 (100.1-131.5) | 112.9 (75.0-117.6) | 114.7 (68.5-129.6) | 108.1 (77.1-122.7) |
| ARC, ×109/L† | 178.1 (72.9-283.4) | 205.5 (136.0-366.4) | 238.4 (227.0-360.6) | 274.1 (125.6-329.6) | 226.8 (29.4-366.0) | 219.3 (80.5-511.0) |
| iBIL, mg/dL‡ | 3.8 (2.1-5.4) | 2.3 (1.6-5.1) | 2.8 (2.0-5.0) | 1.7 (0.5-10.5) | 1.3 (0.7-4.5) | 1.3 (0.8-5.2) |
| LDH, U/L | 374.5 (348-401) | 405.0 (308-543) | 352.0 (180-683) | 381.5 (207-699) | 368.5 (251-683) | 367.0 (186-683) |
| % F cells§ | 62.6 (33.3-91.8) | 50.6 (34.4-75.5) | 26.2 (22.3-30.1) | 36.1 (16.4-67.2) | 54.4 (13.3-64.8) | 54.4 (6.1-76.9) |
ARC, absolute reticulocyte count; HbF, fetal Hb; HbS, hemoglobin S; HU, hydroxyurea; iBIL, indirect bilirubin, LDH, lactate dehydrogenase; MAD, multiple ascending dose; MCV, mean corpuscular volume; OL, open-label.
n = 3 for MAD pooled placebo; n = 7 for MAD1 (300 mg); n = 14 for the 12-week cohort.
n = 3 for MAD pooled placebo.
n = 4 for single dose 700 mg; n = 3 for MAD pooled placebo.
n = 2 for MAD pooled placebo; n = 7 for MAD1 (300 mg); n = 14 for the 12-week cohort.