Publication: A randomized phase I/II trial of HQK-1001, an oral fetal globin gene inducer, in β-thalassaemia intermedia and HbE/β-thalassaemia
Issued Date
2013-05-01
Resource Type
ISSN
13652141
00071048
00071048
Other identifier(s)
2-s2.0-84876810376
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Mahidol University
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SCOPUS
Bibliographic Citation
British Journal of Haematology. Vol.161, No.4 (2013), 587-593
Suggested Citation
Suthat Fucharoen, Adlette Inati, Noppadol Siritanaratku, Swee L. Thein, William C. Wargin, Suzanne Koussa, Ali Taher, Nattawara Chaneim, Michael Boosalis, Ronald Berenson, Susan P. Perrine A randomized phase I/II trial of HQK-1001, an oral fetal globin gene inducer, in β-thalassaemia intermedia and HbE/β-thalassaemia. British Journal of Haematology. Vol.161, No.4 (2013), 587-593. doi:10.1111/bjh.12304 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/32376
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Title
A randomized phase I/II trial of HQK-1001, an oral fetal globin gene inducer, in β-thalassaemia intermedia and HbE/β-thalassaemia
Abstract
β-thalassaemia intermedia (BTI) syndromes cause haemolytic anaemia, ineffective erythropoiesis, and widespread complications. Higher fetal globin expression within genotypes reduces globin imbalance and ameliorates anaemia. Sodium 2,2 dimethylbutyrate (HQK-1001), an orally bioavailable short-chain fatty acid derivative, induces γ-globin expression experimentally and is well-tolerated in normal subjects. Accordingly, a randomized, blinded, placebo-controlled, Phase I/II trial was performed in 21 adult BTI patients (14 with HbE/β0thalassaemia and seven with β+/β0thalassaemia intermedia, to determine effective doses for fetal globin induction, safety, and tolerability. HQK-1001 or placebo were administered once daily for 8 weeks at four dose levels (10, 20, 30, or 40 mg/kg per day), and subjects were monitored for laboratory and clinical events. Pharmacokinetic profiles demonstrated a t1/2of 10-12 h. Adverse events with HQK-1001 treatment were not significantly different from placebo treatment. The 20 mg/kg treatment doses increased median HbF above baseline levels by 6·6% and 4·4 g/l (P < 0·01) in 8/9 subjects; total haemoglobin (Hb) increased by a mean of 11 g/l in 4/9 subjects. These findings identified a safe oral therapeutic which induces fetal globin in BTI. Further investigation of HQK-1001 with longer dosing to definitively evaluate its haematological potential appears warranted. © 2013 John Wiley & Sons Ltd.