Sickle Cell Disease
Conditions
Brief summary
Part A: Change from baseline in Hb through Week 12., Part B: Co-primary endpoints • Hb response (increase from baseline of > 1 g/dL) at Week 48 (based on average of Hb levels at Week 40 and Week 48). • Annualized rate of VOC through end of Week 48. See Section 8.1 for the definition of VOC., Part C: • AUC0-last and AUC0-inf of osivelotor in whole blood and plasma after single dose, and AUC0-24 after multiple dose administration of osivelotor. • Cmax after a single dose, and both Cmax and Cmin after multiple dose administration. • Accumulation ratios based on Cmax and AUC0-24. • % Hb occupancy after multiple dose administration of osivelotor.
Detailed description
Part A: • Hb response at Week 12 (increase from baseline of >1 g/dL). • Change from baseline in hemolysis measures, including indirect bilirubin, absolute and % reticulocytes, and LDH through Week 12. • Incidence of TEAEs, changes in laboratory assessments, ECGs, and vital signs. • Effect on Hb OEC as measured by p50 through Week 12. • AUC, Cmax, Tmax, B:P ratios of these PK parameters after the first dose. Cmin and B:P ratio after multiple dose administration. • % Hb occupancy, Part B: Key Secondary Efficacy Endpoints: • Change from baseline in absolute reticulocyte count at Week 48. • Change from baseline in PROMIS SF Fatigue 13a raw total score at Week 48. • Change from baseline in PROMIS SF Pain Interference 8a raw total score at Week 48., Part C: • Incidence of adverse events, changes in laboratory assessments, ECGs, and vital signs. • Change from baseline in Hb at MD Week 2 (Day 14). • Change from baseline in hemolysis measures, including indirect bilirubin, absolute and % reticulocytes, and LDH at MD Week 2 (Day 14). • RBC count at MD Week 2 (Day 14). • PK parameters after single dose in both plasma and whole blood, including t1/2, Tmax, CL/F, V/F, and B:P ratios. • PK parameters after multiple doses in both plasma and whole
Interventions
Sponsors
Global Blood Therapeutics Inc.
Eligibility
Sex/Gender
All
Age
0 Years to No maximum
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part A: Change from baseline in Hb through Week 12., Part B: Co-primary endpoints • Hb response (increase from baseline of > 1 g/dL) at Week 48 (based on average of Hb levels at Week 40 and Week 48). • Annualized rate of VOC through end of Week 48. See Section 8.1 for the definition of VOC., Part C: • AUC0-last and AUC0-inf of osivelotor in whole blood and plasma after single dose, and AUC0-24 after multiple dose administration of osivelotor. • Cmax after a single dose, and both Cmax and Cmin after multiple dose administration. • Accumulation ratios based on Cmax and AUC0-24. • % Hb occupancy after multiple dose administration of osivelotor. | — |
Secondary
| Measure | Time frame |
|---|---|
| Part A: • Hb response at Week 12 (increase from baseline of >1 g/dL). • Change from baseline in hemolysis measures, including indirect bilirubin, absolute and % reticulocytes, and LDH through Week 12. • Incidence of TEAEs, changes in laboratory assessments, ECGs, and vital signs. • Effect on Hb OEC as measured by p50 through Week 12. • AUC, Cmax, Tmax, B:P ratios of these PK parameters after the first dose. Cmin and B:P ratio after multiple dose administration. • % Hb occupancy, Part B: Key Secondary Efficacy Endpoints: • Change from baseline in absolute reticulocyte count at Week 48. • Change from baseline in PROMIS SF Fatigue 13a raw total score at Week 48. • Change from baseline in PROMIS SF Pain Interference 8a raw total score at Week 48., Part C: • Incidence of adverse events, changes in laboratory assessments, ECGs, and vital signs. • Change from baseline in Hb at MD Week 2 (Day 14). • Change from baseline in hemolysis measures, including indirect bilirubin, absolute and % r | — |
Countries
France, Germany
Outcome results
None listed