A phase I/II, open-label, dose-escalation trial using the once-daily oral chelator deferasirox to treat iron overload in HFE-related hereditary hemochromatosis: Final results

Phatak, P., Brissot, P., Wurster, M., Adams, P. C., Bonkovsky, HL, Gross, J, Malfertheiner, P, McLaren, G. D., Niederau, C., Piperno, A., Powell, L. W., Russo, M., Stoelzel, U., Stremmel, W., Griffel, L., Lynch, N., Zhang, Y. and Pietrangelo, A. (2010). A phase I/II, open-label, dose-escalation trial using the once-daily oral chelator deferasirox to treat iron overload in HFE-related hereditary hemochromatosis: Final results. In: Abstracts of the International Liver Congress™ 2010 – the 45th annual meeting of the European Association for the Study of the Liver (EASL). 45th Annual Meeting of the European Association for the Study of Liver, Vienna, Austria, (S-81-S-81). 14-18 April 2010. doi:10.1016/S0168-8278(10)60189-4


Author Phatak, P.
Brissot, P.
Wurster, M.
Adams, P. C.
Bonkovsky, HL
Gross, J
Malfertheiner, P
McLaren, G. D.
Niederau, C.
Piperno, A.
Powell, L. W.
Russo, M.
Stoelzel, U.
Stremmel, W.
Griffel, L.
Lynch, N.
Zhang, Y.
Pietrangelo, A.
Title of paper A phase I/II, open-label, dose-escalation trial using the once-daily oral chelator deferasirox to treat iron overload in HFE-related hereditary hemochromatosis: Final results
Conference name 45th Annual Meeting of the European Association for the Study of Liver
Conference location Vienna, Austria
Conference dates 14-18 April 2010
Proceedings title Abstracts of the International Liver Congress™ 2010 – the 45th annual meeting of the European Association for the Study of the Liver (EASL)   Check publisher's open access policy
Journal name Journal of Hepatology   Check publisher's open access policy
Place of Publication Amsterdam, Netherlands
Publisher Elsevier BV
Publication Year 2010
Year available 2010
Sub-type Published abstract
DOI 10.1016/S0168-8278(10)60189-4
ISSN 0168-8278
1600-0641
0169-5185
Volume 52
Issue Supp. 1
Start page S-81
End page S-81
Total pages 1
Language eng
Formatted Abstract/Summary
Background and Aims: Hereditary hemochromatosis (HH) is characterized by increased intestinal iron absorption. Consequences of iron overload include organ dysfunction, cirrhosis and hepatocellular carcinoma. Although phlebotomy is the   standard of care, it is contraindicated in patients with severe heart disease or anemia, venous access may be difficult and compliance can be variable. The once-daily, oral iron chelator, deferasirox (Exjade®) may provide an alternative treatment. Results of the 6-month core trial were previously reported; 6-month extension data are reported
here.

Methods:
Patients with HFE C282Y homozygous HH with serum ferritin (SF) 300–2000 ng/mL, transferrin saturation ≥45% and no known history of cirrhosis were enrolled in this dose-escalation study (deferasirox 5, 10 and 15 mg/kg/day). This multicenter study comprised a core and extension phase (both 24 weeks). The primary endpoint was the incidence and severity of adverse events (AEs). Secondary endpoints included change in SF.

Results:
49 patients were enrolled (33 men, 16 women; mean age 50.6 years; mean 3.1 years since HH diagnosis) and received deferasirox 5 (n = 11), 10 (n = 15) or 15 mg/kg/day (n = 23). 37 (75.5%) patients completed the core trial. Of 26 patients who
entered the extension, 23 (88.5%) completed 48 weeks. The most common reasons for discontinuation were AEs, mainly in the 10 and 15 mg/kg/day cohorts. Overall, AEs were dose dependent, including diarrhea, headache and nausea (n = 18, n = 10 and n = 8 in the core and n = 1, n = 1, n = 0 in the extension, respectively). Throughout 48
weeks in the 15 mg/kg/day cohort, six patients experienced ALT >3 x baseline and > upper limit of normal (ULN), and eight patients had serum creatinine ≥33% above baseline and >ULN on two consecutive occasions. SF declined in all cohorts; median reduction was 63.5%, 74.8% and 74.1% in the 5, 10 and 15 mg/kg/day cohorts, respectively; in all cohorts, median SF was <250 ng/mL after receiving deferasirox for 48 weeks.

Conclusions:
Results suggest that deferasirox doses of 5, 10 and 15 mg/kg/day can reduce iron burden in HH patients. Based on the safety and efficacy results, deferasirox 10 mg/kg/day appears to be the most appropriate doses for further study in this patient population.
Copyright © 2011 Elsevier B.V. All rights reserved.
Keyword Gastroenterology & Hepatology
Q-Index Code CX
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Conference Paper
Collections: Non HERDC
School of Medicine Publications
 
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Created: Sun, 23 May 2010, 10:02:19 EST