Actively recruiting clinical trials of antioxidants, antiadhesive, and anti-inflammatory agents in SCD
| Mechanism . | Drug . | Sponsor . | NCT number (study acronym) . | Clinical phase/status . | Study design/intervention . | Number/age . | Outcome . |
|---|---|---|---|---|---|---|---|
| P-selectin antagonist | Crizanlizumab | Novartis Pharmaceuticals | NCT03938454 (SPARTAN) | Phase 2 | IV infusion every 2 wk for first month and then every 4 wk × 51 wk | 56/ ≥ 16 y | Evaluate efficacy in priapism, uncomplicated VOC events |
| NCT04657822 | Phase 4 | Open-label extension study, IV infusion every 2 wk for first month and then every 4 wk | 130/all ages | Evaluate the frequency of treatment-related adverse events | |||
| NCT03474965 | Phase 2 | Open label extension study, IV infusion every 2 wk for first month and then every 4 wk | 119/6 mo-17 y | Pharmacokinetics, pharmacodynamics and safety, pain crisis rate | |||
| Inclacumab | Global Blood Therapeutics | NCT04927247 | Phase 3 | Single IV dose (30 mg/kg) of inclacumab vs placebo after VOC event (that required hospitalization and IV pain medication) | 280/ ≥ 12 y | Evaluate proportion of participants with readmission for VOC within 90 d, time to readmission, pharmacodynamics | |
| NCT04935879 | Phase 3 | Inclacumab (30 mg/kg) vs placebo administered IV every 12 wk for 48 wk | 240/ ≥ 12 y | Safety and effect on VOC including frequency of VOC during treatment period, time to first and second VOC, hospitalization duration | |||
| NCT05348915 | Phase 3 | Open-label extension study, inclacumab (30 mg/kg) IV every 12 wk | 520/ ≥ 12 y | Safety, evaluate annualized rate of VOC, hospitalizations, complicated VOCs, transfusions, pharmacokinetics | |||
| Blockade of fcγriii receptors | IVIG | Albert Einstein College of Medicine | NCT01757418 | Phase 1/2 | Single dose of IVIG vs placebo given within 24 h of hospitalization | 94/12-65 y | Length of VOC, total opioid use, time to end of VOC, in vitro adhesion studies |
| Antioxidant | Glutamine | Ain Shams University | NCT05371184 | Phase 4 | 0.3 gm/kg/dose twice daily orally (up to a maximum of 15 g/dose) for 24 wk | 30/2-18 y | Incidence of pain crisis, change in transcranial Doppler |
| Anti-inflammatory | Rifaximin (antibiotic, decrease aged neutrophils) | Bausch Health Americas Inc | NCT05098028 | Phase 2a | Oral, extended release (high and low dose) vs delayed extended release (high and low dose) vs placebo | 60/18-70 y | Evaluate pharmacokinetics and pharmacodynamics |
| Crovalimab (anticomplement C5 monoclonal antibody) | Hoffmann-La Roche | NCT04912869 (CROSSWALK-a) | Phase 1 | Single IV infusion of crovalimab vs placebo for management of uncomplicated VOC | 30/12-55 y | Safety, adverse events, pharmacokinetics, pharmacodynamics, time to resolution of VOC, cumulative opioid dose, time to discontinuation of parenteral opioids, percentage of participants with VOC complication (ACS, ICU, blood transfusion) | |
| NCT05075824 (CROSSWALK-c) | Phase 2 | IV loading dose of crovalimab on day 1, followed by SQ dose day 2 and then weekly for 3 wk. Monthly maintenance SQ dosing starting week 5 for 48 wk vs placebo. | 90/12-55 y | Evaluated effect on frequency of VOC events, ACS events, duration of hospitalization, change in urine albumin-creatinine ratio, tricuspid regurgitant jet velocity, and PROMIS score | |||
| Tocilizumab (anti- interleukin 6) | University of Chicago | NCT05640271 | Phase 2 | Single 80-mg IV dose at time of ACS diagnosis followed by placebo (50 mL normal saline) 48 h later. Control arm receives placebo first followed by tocilizumab 48 h later. | 200/ ≥ 18 y | Changes in peripheral oxygen saturation, changes in the route, rate, and FiO2 of supplemental oxygen delivery from day 0 to day 4. The time-weighted SaO2/FiO2 ratio will be calculated based on this. | |
| ALXN1820 (bispecific- antiproperdin antibody) | Alexion | NCT05565092 (PHOENIX) | Phase 2a | Open-label study to evaluate multiple dosing regimens (i) 300 mg SQ weekly, (ii) 600 mg SQ every 4 wk, (iii) 300 mg SQ every 2 wk | 30/18-65 y | Safety, pharmacokinetics, changes from baseline in Hb, hemolysis markers, hemopexin, complement activity, and concentration of properdin and complement biomarkers |
| Mechanism . | Drug . | Sponsor . | NCT number (study acronym) . | Clinical phase/status . | Study design/intervention . | Number/age . | Outcome . |
|---|---|---|---|---|---|---|---|
| P-selectin antagonist | Crizanlizumab | Novartis Pharmaceuticals | NCT03938454 (SPARTAN) | Phase 2 | IV infusion every 2 wk for first month and then every 4 wk × 51 wk | 56/ ≥ 16 y | Evaluate efficacy in priapism, uncomplicated VOC events |
| NCT04657822 | Phase 4 | Open-label extension study, IV infusion every 2 wk for first month and then every 4 wk | 130/all ages | Evaluate the frequency of treatment-related adverse events | |||
| NCT03474965 | Phase 2 | Open label extension study, IV infusion every 2 wk for first month and then every 4 wk | 119/6 mo-17 y | Pharmacokinetics, pharmacodynamics and safety, pain crisis rate | |||
| Inclacumab | Global Blood Therapeutics | NCT04927247 | Phase 3 | Single IV dose (30 mg/kg) of inclacumab vs placebo after VOC event (that required hospitalization and IV pain medication) | 280/ ≥ 12 y | Evaluate proportion of participants with readmission for VOC within 90 d, time to readmission, pharmacodynamics | |
| NCT04935879 | Phase 3 | Inclacumab (30 mg/kg) vs placebo administered IV every 12 wk for 48 wk | 240/ ≥ 12 y | Safety and effect on VOC including frequency of VOC during treatment period, time to first and second VOC, hospitalization duration | |||
| NCT05348915 | Phase 3 | Open-label extension study, inclacumab (30 mg/kg) IV every 12 wk | 520/ ≥ 12 y | Safety, evaluate annualized rate of VOC, hospitalizations, complicated VOCs, transfusions, pharmacokinetics | |||
| Blockade of fcγriii receptors | IVIG | Albert Einstein College of Medicine | NCT01757418 | Phase 1/2 | Single dose of IVIG vs placebo given within 24 h of hospitalization | 94/12-65 y | Length of VOC, total opioid use, time to end of VOC, in vitro adhesion studies |
| Antioxidant | Glutamine | Ain Shams University | NCT05371184 | Phase 4 | 0.3 gm/kg/dose twice daily orally (up to a maximum of 15 g/dose) for 24 wk | 30/2-18 y | Incidence of pain crisis, change in transcranial Doppler |
| Anti-inflammatory | Rifaximin (antibiotic, decrease aged neutrophils) | Bausch Health Americas Inc | NCT05098028 | Phase 2a | Oral, extended release (high and low dose) vs delayed extended release (high and low dose) vs placebo | 60/18-70 y | Evaluate pharmacokinetics and pharmacodynamics |
| Crovalimab (anticomplement C5 monoclonal antibody) | Hoffmann-La Roche | NCT04912869 (CROSSWALK-a) | Phase 1 | Single IV infusion of crovalimab vs placebo for management of uncomplicated VOC | 30/12-55 y | Safety, adverse events, pharmacokinetics, pharmacodynamics, time to resolution of VOC, cumulative opioid dose, time to discontinuation of parenteral opioids, percentage of participants with VOC complication (ACS, ICU, blood transfusion) | |
| NCT05075824 (CROSSWALK-c) | Phase 2 | IV loading dose of crovalimab on day 1, followed by SQ dose day 2 and then weekly for 3 wk. Monthly maintenance SQ dosing starting week 5 for 48 wk vs placebo. | 90/12-55 y | Evaluated effect on frequency of VOC events, ACS events, duration of hospitalization, change in urine albumin-creatinine ratio, tricuspid regurgitant jet velocity, and PROMIS score | |||
| Tocilizumab (anti- interleukin 6) | University of Chicago | NCT05640271 | Phase 2 | Single 80-mg IV dose at time of ACS diagnosis followed by placebo (50 mL normal saline) 48 h later. Control arm receives placebo first followed by tocilizumab 48 h later. | 200/ ≥ 18 y | Changes in peripheral oxygen saturation, changes in the route, rate, and FiO2 of supplemental oxygen delivery from day 0 to day 4. The time-weighted SaO2/FiO2 ratio will be calculated based on this. | |
| ALXN1820 (bispecific- antiproperdin antibody) | Alexion | NCT05565092 (PHOENIX) | Phase 2a | Open-label study to evaluate multiple dosing regimens (i) 300 mg SQ weekly, (ii) 600 mg SQ every 4 wk, (iii) 300 mg SQ every 2 wk | 30/18-65 y | Safety, pharmacokinetics, changes from baseline in Hb, hemolysis markers, hemopexin, complement activity, and concentration of properdin and complement biomarkers |
FiO2, fraction of inspired oxygen; ICU, intensive care unit; IVIG, intravenous immunoglobulin; PROMIS, patient-reported outcome measures; SaO2, oxygen saturation; SQ, subcutaneous.