Ongoing clinical studies in thalassemias, SCD, and other red cell disorders
| Mechanism . | Agent . | Study title/NCT/populations . | Clinical phase . | Status . |
|---|---|---|---|---|
| Drug directly targeting erythropoiesis | Luspatercept | NCT04143724 Population: β-thal or HbE/β-thal Age: 6-17 y Enrollment (estimated) N = 54 pts | Phase 2 A phase 2a study of the safety and pharmacokinetics of luspatercept (ACE-536) in pediatric participants under regular transfusions due to (β)-thalassemia | Recruiting |
| NCT05664737 Population: α-thal HbH disease Age: ≥18 y Enrollment (estimated) N = 177 pts | Phase 2 A phase 2, double-blind, randomized, placebo-controlled, multicenter study to determine the efficacy and safety of luspatercept (BMS-986346/ACE-536) for the adults with alpha (α)-thalassemia | Recruiting | ||
| EudraCT number: 2020-005736-30 Population: CDAII (biallelic causative mutations in SEC23B gene alone or associated with other gene variants or monoallelic causative mutations in SEC23B gene in presence of hypoglycosylation of band 3 and/or associated with other gene variants) Age: ≥18 y Enrollment (estimated) N = 40 pts | Phase 2 A phase 2, multicenter, open-label study. Efficacy and safety of luspatercept (ACE-536) in adult patients with CDA II | Active, not recruiting | ||
| Targeting iron homeostasis or heme synthesis | FPN blocker | ViSionSerenity (NCT04817670) Population: HbSS or HbS/β0 thal Age:18-60 y Enrollment (estimated) N = 24 pts | Phase 2 Double-blind, randomized, placebo-controlled, efficacy, and safety study of multiple doses of VIT-2763 in subjects with SCD | Recruiting |
| Bitopertin | NCT05828108 Population: steroid-refractory DBA Age: 18-100 y Enrollment (estimated) N = 30 pts | Phase 1/2 Intrapatient dose-escalation study of the selective GlyT1 inhibitor bitopertin for steroid-refractory Diamond-Blackfan anemia | Recruiting | |
| BEACON (ACTRN12622000799752) Population: EPP and X-linked protoporphyria Age: ≥18 y Enrollment (estimated) N = 22 pts | Phase 2 randomized, open-label study of bitopertin to evaluate the safety, tolerability, efficacy, and protoporphyrin IX (PPIX) concentration in participants with EPP and X-linked protoporphyria (XLP) | Recruiting | ||
| AURORA (NCT05308472) Population: EPP Age: ≥18 y Enrollment N = 75 pts | Phase 2 randomized, double-blind, placebo-controlled study of bitopertin to evaluate the safety, tolerability, efficacy, and PPIX concentrations in participants with EPP | Active, not recruiting | ||
| Metabolic targets | Mitapivat (AG-348) | ENERGIZE (NCT04770753) Population: β-thal with or without α-globin gene mutations, HbE/β-thal, or α-thal/HbH disease Age: ≥18 y Enrolled N = 194 pts | Phase 3 Efficacy and safety of mitapivat in pts with α- or β-NTDT | Active, not recruiting |
| ENERGIZE-T (NCT04770779) Population: β-thal with or without α-globin gene mutations, HbE/β-thal, or α-thal/HbH disease Age: ≥18 y Enrolled N = 258 pts | Phase 3 Efficacy and safety of mitapivat in pts with α- or β-TDT | Active, not recruiting | ||
| SATISFY (NCT05935202) Population: RBC membranopathy or CDAII Age: ≥18 y Enrollment (estimated) N = 25 pts | Phase 2 Safety and efficacy of mitapivat in adult patients with membranopathies | Not yet recruiting | ||
| NCT04610866 Population: HbSS Age: 18-70 y Enrolled N = 15 pts | Phase 1/2 extension of a phase 1 pilot study of mitapivat Safety, tolerability, pharmacokinetics, and pharmacodynamics of long-term mitapivat dosing in subjects with stable SCD | Active, not recruiting | ||
| RISE UP (NCT05031780) Population: HbSS, HbSC, HbS/beta0 thal, HbS/ beta+ thal, or other SCD variants Age: ≥16 y Enrolled N = 277 pts | Phase 2/3 Double-blind, randomized, placebo-controlled, multicenter study to evaluate the efficacy and safety of mitapivat in subjects with SCD | Active, not recruiting | ||
| AG-946 | NCT04536792 Population: SCD Age:18-55 y Enrollment (estimated) N = 118 (actual) N = 122 | Phase 1 A phase 1 study for safety, tolerability, pharmacokinetics, and pharmacodynamics of AG-946 in healthy volunteers and in subjects with SCD | Completed | |
| Etavopivat (FT-4202) | HIBISCUS (NCT04624659) Population: SCD Age: 12-65 y Enrollment (estimated) N = 344 pts | Phase 2/3 An adaptive, randomized, placebo-controlled, double-blind, multicenter study of oral etavopivat, a PK activator in patients with SCD | Recruiting | |
| GLADIOLUS (NCT04987489) Population: SCD; β-thal, HbE/ β-thal or HbH (α-thal), or other thal variant Age: 12-65 y Enrollment (estimated) N = 60 pts | Phase 2 Open-label study to evaluate safety and clinical activity of etavopivat in patients with thalassemia or SCD | Recruiting | ||
| NCT05953584 Population: HbSS, HbSβ0 thal Age: 12-16 y Enrollment (estimated) N = 46 pts | Phase 2 Open-label study to evaluate the activity of etavopivat on transcranial doppler velocities in pediatric patients with SCD who are at increased risk for primary stroke | Recruiting | ||
| NCT05725902 Population: HbSS or HbS/β0 thal Age: 12-21 y Enrollment (estimated) N = 12 pts | Phase 2 Effect of etavopivat on cerebral hemodynamic response in children with SCD | Not yet recruiting | ||
| Targeting hemolysis and the vascular endothelial axis | Hpx (CSL889) | NCT04285827 Population: SCD Age: 18-60 y Enrolled N = 28 pts | Phase 1 A 2-part, phase 1, multicenter, single-dose, open-label study to evaluate the safety, tolerability, and pharmacokinetics of CSL889 in adult patients with SCD | Completed |
| l-Arginine | STArT (NCT04839354) Population: SCD (any genotype) Age: 3-21 y Enrollment (estimated) N = 360 pts | Phase 3 SCD treatment with arginine therapy (STArT) Trial | Recruiting | |
| R34 pK/PD (NCT02447874) Population: HbSS, HbSβ0 thal, Age: 7-21 y Enrollment (estimated) N = 21 pts | Phase 1/2 Arginine therapy for the treatment of VOCs in children with severe SCD | Recruiting | ||
| Complement (AP) Crovalimab | CROSSWALK-a (NCT04912869) Population: HbSS or HbSβ0 thal Age: 12-55 y Enrollment (estimated) N = 30 pts | Phase 1 A phase 1b randomized, placebo-controlled study evaluating the safety, pharmacokinetics, pharmacodynamics, and efficacy of crovalimab for the management of acute uncomplicated VOCs in patients with SCD | Recruiting | |
| CROSSWALK-c (NCT05075824) Population: HbSS or HbSβ0 thal Age:12-55 y Enrollment (estimated) N = 90 pts | Phase 2 A randomized double-blind phase 2a study evaluating the efficacy, safety, pharmacokinetics, and pharmacodynamics of crovalimab as adjunct treatment in prevention of VOCs in SCD | Recruiting | ||
| r-ADAMTS13 (SHP665) | RAISE (NCT03997760) Population: HbSS or HbSβ0 thal Age: 18-65 y Enrolled N = 9 pts | Phase 1 A study of SHP655 (rADAMTS13) in SCD | Completed | |
| ω-3 fatty acid | NCT05758766 Population: HbSS or HbSβ0 thal at steady state Age: 5-18 y Enrollment (estimated) N = 30 pts | Interventional, not applicable Study on use of plat extracts of ω-3 fatty acids to improve outcomes in individuals with SCD | Recruiting | |
| Epeleuton (DS102) | NCT05861453 Population: HbSS or HbSβ0 thal Age: ≥18 y Enrollment (estimated) N = 30 pts | Phase 2 Pharmacokinetics, pharmacodynamics, and safety of epeleuton in patients with SCD | Recruiting | |
| Inclacumab | THRIVE-131 (NCT04935879) Population: HbSS, HbSC, HbS/beta0 thal, HbS/beta+ thal Age: ≥12y Enrollment N = 232 | Phase 3 A randomized, double-blind, placebo-controlled, multicenter study to assess the safety and efficacy of inclacumab in participants with SCD experiencing VOCs | Active, not recruiting | |
| THRIVE-132 (NCT04927247) Population: SCD (any genotype) Age: ≥12y Enrollment N = 72 | Phase 3 A randomized, double-blind, placebo-controlled, multicenter study of a single dose of inclacumab to reduce re-admission in participants with SCD and recurrent VOCs | Completed | ||
| THRIVE-133 OLE (NCT05348915) Population: SCD Age: ≥12 y Enrollment (estimated) N = 520 | Phase 3 An open-label extension study to evaluate the long-term safety of inclacumab administered to participants with SCD, who have participated in an inclacumab clinical trial | Recruiting | ||
| Tocilizumab | NCT05640271 Population: HbSS, HbSC, HbS/beta0 thal, HbS/ beta+ thal Age: ≥18y Enrollment (estimated) N = 200 | Phase 2 Low-dose tocilizumab for acute chest syndrome in pts with SCD | Recruiting |
| Mechanism . | Agent . | Study title/NCT/populations . | Clinical phase . | Status . |
|---|---|---|---|---|
| Drug directly targeting erythropoiesis | Luspatercept | NCT04143724 Population: β-thal or HbE/β-thal Age: 6-17 y Enrollment (estimated) N = 54 pts | Phase 2 A phase 2a study of the safety and pharmacokinetics of luspatercept (ACE-536) in pediatric participants under regular transfusions due to (β)-thalassemia | Recruiting |
| NCT05664737 Population: α-thal HbH disease Age: ≥18 y Enrollment (estimated) N = 177 pts | Phase 2 A phase 2, double-blind, randomized, placebo-controlled, multicenter study to determine the efficacy and safety of luspatercept (BMS-986346/ACE-536) for the adults with alpha (α)-thalassemia | Recruiting | ||
| EudraCT number: 2020-005736-30 Population: CDAII (biallelic causative mutations in SEC23B gene alone or associated with other gene variants or monoallelic causative mutations in SEC23B gene in presence of hypoglycosylation of band 3 and/or associated with other gene variants) Age: ≥18 y Enrollment (estimated) N = 40 pts | Phase 2 A phase 2, multicenter, open-label study. Efficacy and safety of luspatercept (ACE-536) in adult patients with CDA II | Active, not recruiting | ||
| Targeting iron homeostasis or heme synthesis | FPN blocker | ViSionSerenity (NCT04817670) Population: HbSS or HbS/β0 thal Age:18-60 y Enrollment (estimated) N = 24 pts | Phase 2 Double-blind, randomized, placebo-controlled, efficacy, and safety study of multiple doses of VIT-2763 in subjects with SCD | Recruiting |
| Bitopertin | NCT05828108 Population: steroid-refractory DBA Age: 18-100 y Enrollment (estimated) N = 30 pts | Phase 1/2 Intrapatient dose-escalation study of the selective GlyT1 inhibitor bitopertin for steroid-refractory Diamond-Blackfan anemia | Recruiting | |
| BEACON (ACTRN12622000799752) Population: EPP and X-linked protoporphyria Age: ≥18 y Enrollment (estimated) N = 22 pts | Phase 2 randomized, open-label study of bitopertin to evaluate the safety, tolerability, efficacy, and protoporphyrin IX (PPIX) concentration in participants with EPP and X-linked protoporphyria (XLP) | Recruiting | ||
| AURORA (NCT05308472) Population: EPP Age: ≥18 y Enrollment N = 75 pts | Phase 2 randomized, double-blind, placebo-controlled study of bitopertin to evaluate the safety, tolerability, efficacy, and PPIX concentrations in participants with EPP | Active, not recruiting | ||
| Metabolic targets | Mitapivat (AG-348) | ENERGIZE (NCT04770753) Population: β-thal with or without α-globin gene mutations, HbE/β-thal, or α-thal/HbH disease Age: ≥18 y Enrolled N = 194 pts | Phase 3 Efficacy and safety of mitapivat in pts with α- or β-NTDT | Active, not recruiting |
| ENERGIZE-T (NCT04770779) Population: β-thal with or without α-globin gene mutations, HbE/β-thal, or α-thal/HbH disease Age: ≥18 y Enrolled N = 258 pts | Phase 3 Efficacy and safety of mitapivat in pts with α- or β-TDT | Active, not recruiting | ||
| SATISFY (NCT05935202) Population: RBC membranopathy or CDAII Age: ≥18 y Enrollment (estimated) N = 25 pts | Phase 2 Safety and efficacy of mitapivat in adult patients with membranopathies | Not yet recruiting | ||
| NCT04610866 Population: HbSS Age: 18-70 y Enrolled N = 15 pts | Phase 1/2 extension of a phase 1 pilot study of mitapivat Safety, tolerability, pharmacokinetics, and pharmacodynamics of long-term mitapivat dosing in subjects with stable SCD | Active, not recruiting | ||
| RISE UP (NCT05031780) Population: HbSS, HbSC, HbS/beta0 thal, HbS/ beta+ thal, or other SCD variants Age: ≥16 y Enrolled N = 277 pts | Phase 2/3 Double-blind, randomized, placebo-controlled, multicenter study to evaluate the efficacy and safety of mitapivat in subjects with SCD | Active, not recruiting | ||
| AG-946 | NCT04536792 Population: SCD Age:18-55 y Enrollment (estimated) N = 118 (actual) N = 122 | Phase 1 A phase 1 study for safety, tolerability, pharmacokinetics, and pharmacodynamics of AG-946 in healthy volunteers and in subjects with SCD | Completed | |
| Etavopivat (FT-4202) | HIBISCUS (NCT04624659) Population: SCD Age: 12-65 y Enrollment (estimated) N = 344 pts | Phase 2/3 An adaptive, randomized, placebo-controlled, double-blind, multicenter study of oral etavopivat, a PK activator in patients with SCD | Recruiting | |
| GLADIOLUS (NCT04987489) Population: SCD; β-thal, HbE/ β-thal or HbH (α-thal), or other thal variant Age: 12-65 y Enrollment (estimated) N = 60 pts | Phase 2 Open-label study to evaluate safety and clinical activity of etavopivat in patients with thalassemia or SCD | Recruiting | ||
| NCT05953584 Population: HbSS, HbSβ0 thal Age: 12-16 y Enrollment (estimated) N = 46 pts | Phase 2 Open-label study to evaluate the activity of etavopivat on transcranial doppler velocities in pediatric patients with SCD who are at increased risk for primary stroke | Recruiting | ||
| NCT05725902 Population: HbSS or HbS/β0 thal Age: 12-21 y Enrollment (estimated) N = 12 pts | Phase 2 Effect of etavopivat on cerebral hemodynamic response in children with SCD | Not yet recruiting | ||
| Targeting hemolysis and the vascular endothelial axis | Hpx (CSL889) | NCT04285827 Population: SCD Age: 18-60 y Enrolled N = 28 pts | Phase 1 A 2-part, phase 1, multicenter, single-dose, open-label study to evaluate the safety, tolerability, and pharmacokinetics of CSL889 in adult patients with SCD | Completed |
| l-Arginine | STArT (NCT04839354) Population: SCD (any genotype) Age: 3-21 y Enrollment (estimated) N = 360 pts | Phase 3 SCD treatment with arginine therapy (STArT) Trial | Recruiting | |
| R34 pK/PD (NCT02447874) Population: HbSS, HbSβ0 thal, Age: 7-21 y Enrollment (estimated) N = 21 pts | Phase 1/2 Arginine therapy for the treatment of VOCs in children with severe SCD | Recruiting | ||
| Complement (AP) Crovalimab | CROSSWALK-a (NCT04912869) Population: HbSS or HbSβ0 thal Age: 12-55 y Enrollment (estimated) N = 30 pts | Phase 1 A phase 1b randomized, placebo-controlled study evaluating the safety, pharmacokinetics, pharmacodynamics, and efficacy of crovalimab for the management of acute uncomplicated VOCs in patients with SCD | Recruiting | |
| CROSSWALK-c (NCT05075824) Population: HbSS or HbSβ0 thal Age:12-55 y Enrollment (estimated) N = 90 pts | Phase 2 A randomized double-blind phase 2a study evaluating the efficacy, safety, pharmacokinetics, and pharmacodynamics of crovalimab as adjunct treatment in prevention of VOCs in SCD | Recruiting | ||
| r-ADAMTS13 (SHP665) | RAISE (NCT03997760) Population: HbSS or HbSβ0 thal Age: 18-65 y Enrolled N = 9 pts | Phase 1 A study of SHP655 (rADAMTS13) in SCD | Completed | |
| ω-3 fatty acid | NCT05758766 Population: HbSS or HbSβ0 thal at steady state Age: 5-18 y Enrollment (estimated) N = 30 pts | Interventional, not applicable Study on use of plat extracts of ω-3 fatty acids to improve outcomes in individuals with SCD | Recruiting | |
| Epeleuton (DS102) | NCT05861453 Population: HbSS or HbSβ0 thal Age: ≥18 y Enrollment (estimated) N = 30 pts | Phase 2 Pharmacokinetics, pharmacodynamics, and safety of epeleuton in patients with SCD | Recruiting | |
| Inclacumab | THRIVE-131 (NCT04935879) Population: HbSS, HbSC, HbS/beta0 thal, HbS/beta+ thal Age: ≥12y Enrollment N = 232 | Phase 3 A randomized, double-blind, placebo-controlled, multicenter study to assess the safety and efficacy of inclacumab in participants with SCD experiencing VOCs | Active, not recruiting | |
| THRIVE-132 (NCT04927247) Population: SCD (any genotype) Age: ≥12y Enrollment N = 72 | Phase 3 A randomized, double-blind, placebo-controlled, multicenter study of a single dose of inclacumab to reduce re-admission in participants with SCD and recurrent VOCs | Completed | ||
| THRIVE-133 OLE (NCT05348915) Population: SCD Age: ≥12 y Enrollment (estimated) N = 520 | Phase 3 An open-label extension study to evaluate the long-term safety of inclacumab administered to participants with SCD, who have participated in an inclacumab clinical trial | Recruiting | ||
| Tocilizumab | NCT05640271 Population: HbSS, HbSC, HbS/beta0 thal, HbS/ beta+ thal Age: ≥18y Enrollment (estimated) N = 200 | Phase 2 Low-dose tocilizumab for acute chest syndrome in pts with SCD | Recruiting |
AP, alternative pathway; HbE, hemoglobin E; HbH, hemoglobin H; HbS, hemoglobin S; HbSS, homozygous hemoglobin S; HbSC, hemoglobin SC; NCT, National Clinical Trial; pts, patients; RBC, red blood cells; thal, thalassemia; TD, transfusion dependent.
∗Studies outcomes and dosages are reported in supplemental Table 2.