Clinical trials update – Aug. 2017 to Apr. 2018

Important clinical trials published since Aug. 2017


LentiGlobin gene therapy

  • Autologous CD34+ cells transduced with the BB305 lentiviral vector.
  • An initial phase 1/2 study [Northstar (HGB-204)] in 22 β-thalassaemia patients showed transfusion-independency for non-β0/β0 genotypes and 60% reduction in transfuions in β0/β0 genotype. The results were published in N Engl J Med, in April 19, 2018.
  • An ongoing phase 2 study (HGB-205) evaluates LentiGlobin gene therapy in TDT and severe SCD.
  • An ongoing phase 3 trial [Northstar-2 (HGB-207)] evaluates LentiGlobin gene therapy in TDT with non-β0/β0 genotypes.



  • An agent that regulates hemoglobin gene expression, used for the treatment of other haematological conditions, such as myelofibrosis and resistant to hydroxyurea polycythemia vera.
  • A Phase 2a trial (TRUTH) in 30 transfusion-dependent β-thalassemia with splenomegaly showed that ruxolitinib therapy for 30 weeks resulted in slight improvement in pre-transfusion haemoglobin levels with a noticeable reduction in spleen size, rendering the drug a promising alternative to splenectomy. The results were published as a research letter in Blood, in Jan. 11, 2018.


Long-term safety of deferiprone in children: the DEEP-3 observational study

  • The safety of deferiprone, either alone or in combination with deferoxamine, was evaluated in 297 patients from 16 hospitals in 6 Mediterranean countries, who had been started on deferiprone before the age of 18; 60% of patient aged <10 and 38% <6. Patients were followed for a median of 2 years and the incidence of adverse drug reactions were in line with available data in older populations (Haematologica 2018).


New oral chelator SP-420

  • A phase 1 study evaluated the safety and pharmacokinetics of a novel oral iron chelator of the desferrithiocin class with the code name SP-420 in 24 TDT patients. The study was terminated early due to renal adverse events including proteinuria, increase in serum creatinine and one case of Fanconi syndrome (Am J Hematol, Dec. 2017).


Treatment of HCV with direct-acting antiviral agents (DAA) in haemoglobinopathies

  • An observational study in 139 Italian patients with hemoglobinopathies, chronic HCV infection and advanced liver fibrosis showed that treatment with DAA had similar safety and efficacy with that observed in cirrhotic patients without hemoglobinopathies. The sustained viral response at 12 weeks post-treatment was 94% (Am J Hematol, Dec. 2017).



  • Calcium channel blocker, used for the treatment of hypertension and coronary artery disease, that may prevent iron entry into cardiomyocytes.
  • Small clinical trials showed greater reduction in myocardial iron by MRI T2* when added on top of iron chelation. A recently published study in 56 patients confirmed these results (Eur J Haematol, Dec. 2017).
  • The ongoing randomized trial (CANALI) evaluates amlodipine on top of deferasirox on cardiac iron in TDT patients with moderate cardiac iron overload (MRI T2* 10-20 ms).


Intracellular iron overload in lymphocytes may lead to immune dysfunction

  • In a case-control study in 66 thalassaemia major patients, intracellular iron overload caused lymphocyte DNA fragmentation associated with increased susceptibility to infections (Eur J Haematol, Nov 2017).



Other ongoing trials



  • Luspatercept promotes the differentiation and maturation of late-stage erythrocyte precursors by acting as a ligand trap for members of the TGF-β superfamily, the increased signaling of which inhibits erythrocyte maturation. This mechanism of action is distinct from that of erythropoiesis-stimulating agents (ESAs), which stimulate the proliferation of early-stage erythrocyte precursors.
  • Promising results by two phase 2 trials in TDT and NTDT (sustained increase in hemoglobin levels with reduction of transfusion requirement, reduction of liver iron overload and improvement in quality of life).
  • An ongoing randomized, placebo-controlled phase 3 trial (BELIEVE) evaluates luspatercept (at 1mg/kg titrated to 1.25 mg/kg, subcutaneously every 3 weeks) in 300 patients with TDT; primary efficacy endpoint, proportion of patients with transfusion reduction of 33% of higher. First results expected by June 2018.
  • Another ongoing phase 2 trial (BEYOND) in NTD-thalassemia.



  • Same mechanism of action with luspatercept
  • Testing in thalassaemia has been stopped and the drug has been retargeted to the treatment of pulmonary hypertension in non haemoglobinopathy patients.



  • A novel blood processing system to enhance safety of blood transfusions in terms o blood-borne infections and perhaps transfusion reactions,
  • A US Phase 3 trial showed that INTERCEPT red cells were non-inferior to control red cells in terms of myocardial infarction, renal failure or death.
  • A similar EU Phase 3 trial is ongoing.
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