Primary endpoint and selected secondary and exploratory biochemical endpoints in the intention-to-treat population
| Statistic/ category . | SC411 . | . | |||
|---|---|---|---|---|---|
| Dose level 1 (n = 16) . | Dose level 2 (n = 18) . | Dose level 3 (n = 16) . | Pooled (n = 50) . | Placebo (n = 17) . | |
| Primary endpoint: DHA + EPA blood cell membrane levels at week 4 | |||||
| Baseline (SD), μg/mL | 36.32 (11.74) | 38.59 (11.92) | 36.66 (14.70) | 37.28 (12.56) | 44.64 (18.30) |
| Week 4 (SD), μg/mL | 74.71 (20.63) | 108.40 (43.38) | 99.38 (24.90) | 96.01 (34.66) | 43.74 (18.82) |
| Change vs baseline (95% CI), %* | 109.00 (46.67-171.33) | 163.78 (108.32-219.24) | 170.84 (90.25-251.42) | 147.87 (105.54-190.21) | 28.61 (−50.07-107.29) |
| P value vs baseline | .0007 | <.0001 | <.0001 | <.0001 | .4730 |
| P value vs placebo | .0814 | .0037 | .0096 | .0043 | |
| Biomarkers associated with SCD pathophysiology at week 8 | |||||
| Hemoglobin | |||||
| Baseline (SD), μg/mL | 9.06 (1.23) | 8.84 (1.34) | 9.66 (1.47) | 9.18 (1.37) | 8.96 (0.89) |
| Week 8 (SD), μg/mL | 10.29 (1.16) | 9.58 (1.21) | 9.63 (1.33) | 9.79 (1.25) | 9.43 (0.96) |
| Change vs baseline (95% CI), g/dL† | 0.97 (0.51-1.42) | 0.70 (0.31-1.09) | 0.01 (−0.37 to 0.39) | 0.56 (0.31-0.81) | 0.33 (−0.11 to 0.78) |
| P value vs baseline | <.0001 | .0006 | .9402 | <.0001 | .1389 |
| P value vs placebo | .0389 | .2010 | .2667 | .3488 | |
| Reticulocytes | |||||
| Baseline (SD), % | 6.65 (2.82) | 7.52 (3.90) | 6.25 (2.83) | 6.83 (3.23) | 6.66 (2.91) |
| Week 8 (SD), % | 5.02 (1.55) | 5.85 (2.71) | 5.53 (2.81) | 5.51 (2.46) | 5.76 (3.02) |
| Change vs baseline (95% CI), %† | −0.98 (−2.3 to 0.3) | −0.86 (−1.9 to 0.2) | −0.57 (−1.7 to 0.5) | −0.80 (−1.5 to −0.1) | −0.07 (−1.3 to 1.2) |
| P value vs baseline | .1292 | .1165 | .2981 | .0266 | .9051 |
| P value vs placebo | .2786 | .3227 | .5320 | .2744 | |
| Exploratory endpoints: biomarkers associated with SCD at week 8 | |||||
| E-selectin | |||||
| Baseline (SD), ng/mL | 57.86 (19.32) | 72.10 (41.63) | 62.48 (24.56) | 64.74 (30.97) | 53.34 (19.77) |
| Week 8 (SD), ng/mL | 57.17 (17.78) | 60.77 (33.40) | 59.30 (23.38) | 59.23 (28.84) | 53.06 (19.88) |
| Change vs baseline (95% CI), ng/mL† | −2.89 (−10.8 to 5.0) | −8.95 (−15.1 to −2.8) | −1.60 (−8.1 to 5.0) | −4.48 (−8.8 to −0.2) | 1.74 (−5.4 to 8.9) |
| P value vs baseline | .4682 | .0052 | .6265 | .0429 | .6281 |
| P value vs placebo | .3435 | .0219 | .4691 | .1068 | |
| D-dimer | |||||
| Baseline (SD), μg/mL | 1.66 (2.87) | 1.18 (1.0) | 1.16 (0.73) | 1.33 (1.74) | 1.36 (0.69) |
| Week 8 (SD), μg/mL | 1.12 (0.75) | 0.71 (0.36) | 1.17 (1.00) | 0.99 (0.76) | 2.58 (3.02) |
| D-dimer change vs baseline (95% CI), μg/mL | −0.31 (−1.16 to 0.54) | −0.63 (−1.33 to 0.06) | −0.02 (−0.81 to 0.77) | −0.32 (−0.81 to 0.17) | 0.54 (−0.27 to 1.34) |
| P value vs baseline | .4683 | .0728 | .9541 | .1926 | .1845 |
| P value vs placebo | .1216 | .0250 | .3009 | .0521 | |
| Statistic/ category . | SC411 . | . | |||
|---|---|---|---|---|---|
| Dose level 1 (n = 16) . | Dose level 2 (n = 18) . | Dose level 3 (n = 16) . | Pooled (n = 50) . | Placebo (n = 17) . | |
| Primary endpoint: DHA + EPA blood cell membrane levels at week 4 | |||||
| Baseline (SD), μg/mL | 36.32 (11.74) | 38.59 (11.92) | 36.66 (14.70) | 37.28 (12.56) | 44.64 (18.30) |
| Week 4 (SD), μg/mL | 74.71 (20.63) | 108.40 (43.38) | 99.38 (24.90) | 96.01 (34.66) | 43.74 (18.82) |
| Change vs baseline (95% CI), %* | 109.00 (46.67-171.33) | 163.78 (108.32-219.24) | 170.84 (90.25-251.42) | 147.87 (105.54-190.21) | 28.61 (−50.07-107.29) |
| P value vs baseline | .0007 | <.0001 | <.0001 | <.0001 | .4730 |
| P value vs placebo | .0814 | .0037 | .0096 | .0043 | |
| Biomarkers associated with SCD pathophysiology at week 8 | |||||
| Hemoglobin | |||||
| Baseline (SD), μg/mL | 9.06 (1.23) | 8.84 (1.34) | 9.66 (1.47) | 9.18 (1.37) | 8.96 (0.89) |
| Week 8 (SD), μg/mL | 10.29 (1.16) | 9.58 (1.21) | 9.63 (1.33) | 9.79 (1.25) | 9.43 (0.96) |
| Change vs baseline (95% CI), g/dL† | 0.97 (0.51-1.42) | 0.70 (0.31-1.09) | 0.01 (−0.37 to 0.39) | 0.56 (0.31-0.81) | 0.33 (−0.11 to 0.78) |
| P value vs baseline | <.0001 | .0006 | .9402 | <.0001 | .1389 |
| P value vs placebo | .0389 | .2010 | .2667 | .3488 | |
| Reticulocytes | |||||
| Baseline (SD), % | 6.65 (2.82) | 7.52 (3.90) | 6.25 (2.83) | 6.83 (3.23) | 6.66 (2.91) |
| Week 8 (SD), % | 5.02 (1.55) | 5.85 (2.71) | 5.53 (2.81) | 5.51 (2.46) | 5.76 (3.02) |
| Change vs baseline (95% CI), %† | −0.98 (−2.3 to 0.3) | −0.86 (−1.9 to 0.2) | −0.57 (−1.7 to 0.5) | −0.80 (−1.5 to −0.1) | −0.07 (−1.3 to 1.2) |
| P value vs baseline | .1292 | .1165 | .2981 | .0266 | .9051 |
| P value vs placebo | .2786 | .3227 | .5320 | .2744 | |
| Exploratory endpoints: biomarkers associated with SCD at week 8 | |||||
| E-selectin | |||||
| Baseline (SD), ng/mL | 57.86 (19.32) | 72.10 (41.63) | 62.48 (24.56) | 64.74 (30.97) | 53.34 (19.77) |
| Week 8 (SD), ng/mL | 57.17 (17.78) | 60.77 (33.40) | 59.30 (23.38) | 59.23 (28.84) | 53.06 (19.88) |
| Change vs baseline (95% CI), ng/mL† | −2.89 (−10.8 to 5.0) | −8.95 (−15.1 to −2.8) | −1.60 (−8.1 to 5.0) | −4.48 (−8.8 to −0.2) | 1.74 (−5.4 to 8.9) |
| P value vs baseline | .4682 | .0052 | .6265 | .0429 | .6281 |
| P value vs placebo | .3435 | .0219 | .4691 | .1068 | |
| D-dimer | |||||
| Baseline (SD), μg/mL | 1.66 (2.87) | 1.18 (1.0) | 1.16 (0.73) | 1.33 (1.74) | 1.36 (0.69) |
| Week 8 (SD), μg/mL | 1.12 (0.75) | 0.71 (0.36) | 1.17 (1.00) | 0.99 (0.76) | 2.58 (3.02) |
| D-dimer change vs baseline (95% CI), μg/mL | −0.31 (−1.16 to 0.54) | −0.63 (−1.33 to 0.06) | −0.02 (−0.81 to 0.77) | −0.32 (−0.81 to 0.17) | 0.54 (−0.27 to 1.34) |
| P value vs baseline | .4683 | .0728 | .9541 | .1926 | .1845 |
| P value vs placebo | .1216 | .0250 | .3009 | .0521 | |
LS Means and LS mean differences are from a mixed-model repeated-measures analysis with baseline blood cell DHA+EPA, HU use, age group, baseline disease severity, and treatment as covariates. The model uses subject as a repeated measure with a compound symmetry covariance structure and includes a visit by treatment interaction. Contrasts, dose trend, and P values are produced inside the model.
LS means and LS mean differences are from a mixed-model repeated-measures analysis with each parameter's respective baseline, HU use, age group, baseline disease severity, visit, and treatment as covariates, and subject as a random variable. The model uses subject as a repeated measure with an unstructured covariance structure and includes a visit by treatment interaction. Contrasts and P values are produced inside the model.