Trials · Topics · Hemoglobinopathies
Hemoglobinopathies clinical trials
20 Hemoglobinopathies trials (Classical Hematology) summarized for fellows and board review, newest first within each disease. Each summary covers design, results, toxicity and what changed in practice.
Jump to: Sickle Cell · Thalassemia · Hemolytic Anemia
Sickle Cell (14)
- BEACON (RISTO-CEL IN SCD) NEJM 2026Risto-cel produced rapid engraftment, durable HbF expression, and near-complete elimination of HbS, with no investigator-reported severe VOEs after engraftment. Base...
- Exa-cel in Children (CLIMB THAL-141 / SCD-151) NEJM 2026Exa-cel produced transfusion independence (TDT) and freedom from severe vaso-occlusive crises (SCD) in all evaluable children 5-11 years followed ≥16 months...
- HOPE Kids 2 trial Am J Hematol 2026Voxelotor significantly reduced CBFV vs placebo in children with SCD and conditional TCD velocities, supporting a biologic effect of HbS polymerization inhibition on...
- RUBY (RENI-CEL IN SCD) NEJM 2026Reni-cel produced normalization of hemoglobin levels and marked elevation of HbF, with complete absence of VOEs in 27/28 patients. Despite early termination, these...
- STArT trial (IV arginine for SCD pain) JAMA 2026IV arginine did not shorten time to crisis resolution, reduce parenteral opioid use, or improve pain scores compared with placebo in children and young adults...
- ZIPS-2 trial (zinc for infection prevention in SCA) JAMA 2026Daily zinc sulfate 20 mg reduced all-cause infections by roughly 38% (adjusted IRR 0.62) over 6 months in Ugandan children under 5 years with sickle cell anemia, on a...
- CLIMB-SCD-121 NEJM 2024A single exa-cel infusion eliminated severe VOC in 97% of evaluable patients with severe sickle cell disease, with 100% free from VOC hospitalization, representing a...
- HGB-206 NEJM 2022Lovo-cel produced sustained HbA-T87Q and complete resolution of severe VOC in all 25 evaluable SCD patients, providing proof-of-concept for lentiviral gene-addition...
- HOPE NEJM 2019Voxelotor significantly improved hemoglobin and reduced hemolysis markers in SCD but did not reduce VOC rates. FDA approved October 2019 based on the surrogate Hgb...
- SUSTAIN NEJM 2017Crizanlizumab 5 mg/kg reduced annual VOC rate by 45% versus placebo in SCD patients with ≥2 prior VOC, supporting P-selectin as a therapeutic target. FDA approved...
- TWiTCH Lancet 2016Hydroxyurea was non-inferior to chronic transfusion for maintaining normal TCD velocity in high-risk SCD children who had previously normalized on transfusion, while...
- BABY HUG Lancet 2011Hydroxyurea did not preserve splenic or renal function in infants with SCD (primary endpoints not met), but substantially reduced clinical events including pain...
- STOP-2 NEJM 2005Discontinuing chronic transfusions in SCD patients with previously normalized TCD resulted in rapid TCD reversion and stroke events, establishing that transfusions...
- STOP NEJM 1998Chronic transfusion therapy reduced stroke risk by over 90% in children with SCD and TCD ≥200 cm/s, establishing TCD screening and prophylactic transfusion as the...
Thalassemia (5)
- EDITHAL (RENI-CEL IN THALASSEMIA) NEJM 2026All 9 patients with TD-TDT achieved transfusion independence with reni-cel, with sustained hemoglobin and HbF levels. Despite small numbers and early termination...
- ENERGIZE-T trial Lancet 2026Mitapivat significantly reduced transfusion burden versus placebo in transfusion-dependent alpha- or beta-thalassemia and was generally well tolerated. It is the...
- ENERGIZE Lancet 2025Mitapivat significantly improved hemoglobin levels in adults with NTD alpha- or beta-thalassemia, providing the first evidence of an effective oral disease-modifying...
- HGB-207+212 NEJM 2022Beti-cel achieved transfusion independence in 89% of non-β0/β0 and 64% of β0/β0 patients with transfusion-dependent β-thalassemia, with durable Hgb responses...
- BELIEVE NEJM 2020Luspatercept significantly reduced transfusion burden in adults with transfusion-dependent beta-thalassemia, with 21% achieving ≥33% reduction vs 4.5% on placebo...
Hemolytic Anemia (1)
- ACTIVATE NEJM 2022Mitapivat significantly increased hemoglobin levels in transfusion-independent adult PK deficiency patients vs placebo (40% vs 0% response rate), establishing the...