Journal: Hematology: the American Society of Hematology Education Program

Article Title: Using disease-modifying therapies in sickle cell disease

doi: 10.1182/hematology.2023000485

Figure Lengend Snippet: Actively recruiting clinical trials of antisickling agents in SCD

Article Snippet: GBT021601-012 Global Blood Therapeutics NCT05431088 (GBT021601-021) Phase 2/3 Initial 1:1 randomization to 100 mg and 150 mg, after review of safety data of 150 mg, then randomization 1:1:1 to 100 mg, 150 mg, and 200 mg 480/6 mo-65 y Safety, pharmacokinetics, proportion of participants with increase in Hb >1 gm/dL at week 48 Allosteric activator of RBC pyruvate kinase-R Mitapivat sulfate (AG-348) Agios Pharmaceuticals NCT05031780 (RISE UP) Phase 2/3 Phase 2: oral, twice daily 50-mg dose vs 100-mg dose vs placebo × 12 wk followed by open-label extension period for 216 wk Phase 3: based on phase 2 results either 50 mg or 100 mg twice daily vs placebo for 52 wk followed by open label extension period for 216 wk 267/ ≥ 16 y Safety, adverse events, change in Hb, effect on hemolysis, effect on annualized rate of pain crisis, pharmacokinetics, pharmacodynamics, QOL measures AG- 946 Agios Pharmaceuticals NCT04536792 Phase 1 Single and multiple ascending dose study Part 1: single dose Part 2: once daily for 14 d Part 3: once daily for 28 d 64/18-70 y Safety, tolerability, pharmacokinetics, pharmacodynamics Etavopivat (FT 4202) Forma Therapeutics NCT04987489 Phase 2 Open label, 400 mg once daily in transfusion-dependent sickle cell participants and in transfusion and non–transfusion dependent thalassemia participants 60/12-65 y Safety, evaluate proportion of participants with reduction in blood transfusion requirement, change in Hb, ferritin, and liver iron concentration NCT04624659 (HIBISCUS) Phase 2/3 Phase 2: once daily, 200-mg dose vs 400-mg dose vs placebo for 24 wk Phase 3: based on phase 2 results either 200 mg or 400 mg once daily vs placebo for 28 wk, followed by 52-wk open-label extension period 344/12-65 y Safety, change in Hb, markers of hemolysis, effect on annualized pain crisis rate, patient reported outcome measures (PROMIS) Open in a separate window ACR, albumin creatinine ratio; BUN, serum urea nitrogen; ECG, electrocardiogram; eGFR, estimated glomerular filtration rate;.

Techniques: Extraction, Concentration Assay