Table 2.
Actively recruiting clinical trials of antisickling agents in SCD
| Mechanism | Drug | Sponsor | NCT number (study acronym) | Clinical phase | Study design/Intervention | Number/age | Outcomes |
|---|---|---|---|---|---|---|---|
| HbF induction | Hydroxyurea | ADDMEDICA SASA |
NCT03806452 (SIKAMIC) |
Phase 2 | Oral 15 mg/kg/d for 6 mo vs placebo | 120/ ≥ 18 y | Proportion of patients with at least a 30% decrease in ACR, mean change in GFR, change in ACR, systolic blood pressure, adverse events. |
| Children's Hospital Medical Center, Cincinnati |
NCT03789591 (HOPS) |
Phase 3 | Starting hydroxyurea dose 20 mg/kg/d vs PK-guided initial hydroxyurea dose | 116/6 mo-21 y | Evaluate HbF, F cells, gene-expression patterns | ||
|
NCT02286154 (TREAT) |
N/A | Open-label, single-arm study Old cohort: includes participants already on hydroxyurea upon study entry New cohort: includes participants starting hydroxyurea with starting dose predicted using PK/PD data |
150/6 mo-21 y | Evaluate time to reach maximum tolerated dose, hydroxyurea adherence, neurological function (TCD), splenic (pit count), kidney (BUN/creatinine, urinalysis, cystatin-c) and cardiac function (echo/ECG) | |||
| Nicotinamide vs THU and decitabine | EpiDestiny Inc; National Institutes of Health; NHLBI | NCT04055818 | Phase 1 | Oral nicotinamide vs THU plus decitabine for 12 wk followed by combination for a further 12 wk | 20/ ≥ 18 y | Compare effect of oral nicotinamide vs THU-decitabine and in combination on Hb level at week 12 | |
| Allosteric modifier (to the R-state) | Voxelotor (formerly GBT440) | Global Blood Therapeutics |
NCT02850406 (HOPE Kids) |
Phase 2a | Oral, open-label, single- and multiple-doses study Part A: single dose Part B: 24 wk Part C: 48 wk |
125/4-17 y | Pharmacokinetics, change in Hb, effect on hemolysis, TCD velocity, safety |
| NCT04188509 | Phase 3 | Oral, open-label | 50/4-18 y | Evaluate safety and tolerability, SCD-related complications | |||
| NCT04335721 | Phase 1/2 | Open label, voxelotor vs standard of care (observation) | 12/ ≥ 18 y | Evaluate change in albuminuria and other kidney function measures (24-h urine protein, eGFR, serum creatinine, serum cystatin C) | |||
|
NCT05561140 (RESOLVE) |
Phase 3 | Oral daily voxelotor vs placebo for 12 wk | 80/ ≥ 12 y | Evaluate effect on healing of leg ulcers, time to resolution of target ulcer, change in total surface area of target ulcer, and incidence of new ulcers | |||
| NCT05228834 | Phase 3 | Oral daily voxelotor vs placebo for 12 wk | 80/8-17 y | Evaluate change in executive abilities composite score, processing speed, nonexecutive cognitive abilities, change in hematological parameters, HRQOL score | |||
| Robert Clark Brown | NCT05018728 | Phase 2 | Oral daily voxelotor × 12 wk | 50/4-17 y | Change in cerebral blood flow, oxygen extraction fraction, cerebral metabolic rate of oxygen, Hb, voxelotor-modified Hb | ||
| Emory University |
NCT05018728 (VoxSCAN) |
Phase 2 | Open label, once daily for 12 wk | 12/4-17 y | Evaluate effect on cerebral hemodynamics including cerebral blood flow, oxygen extraction fraction. | ||
| 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) |
ACR, albumin creatinine ratio; BUN, serum urea nitrogen; ECG, electrocardiogram; eGFR, estimated glomerular filtration rate;
HRQOL, health-related quality of life; N/A, not available; PK/PD, pharmacokinetics/pharmacodynamics; R-state, relaxed state; QOL, quality of life; THU, tetrahydrouridine.