Thromb Haemost 2013; 109(02): 248-254
DOI: 10.1160/TH12-06-0447
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Phase II prospective open-label trial of recombinant interleukin-11 in desmopressin-unresponsive von Willebrand disease and mild or moderate haemophilia A

Margaret V. Ragni
1   Department of Medicine, Division of Hematology/Oncology and Vascular Medicine Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
2   Haemophilia Center of Western Pennsylvania, Pittsburgh, Pennsylvania, USA
,
Enrico M. Novelli
1   Department of Medicine, Division of Hematology/Oncology and Vascular Medicine Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
2   Haemophilia Center of Western Pennsylvania, Pittsburgh, Pennsylvania, USA
,
Anila Murshed
2   Haemophilia Center of Western Pennsylvania, Pittsburgh, Pennsylvania, USA
,
Elizabeth P. Merricks
3   Department of Pathology and Laboratory Medicine/ Francis Owen Blood Research Laboratory, University of North Carolina, Chapel Hill, North Carolina, USA
,
Mark T. Kloos
3   Department of Pathology and Laboratory Medicine/ Francis Owen Blood Research Laboratory, University of North Carolina, Chapel Hill, North Carolina, USA
,
Timothy C. Nichols
3   Department of Pathology and Laboratory Medicine/ Francis Owen Blood Research Laboratory, University of North Carolina, Chapel Hill, North Carolina, USA
› Author Affiliations

Financial support: The Pennsylvania Department of Health State SAP #04100000330 (MVR); and CTRC/ CTSI grant: NIH/NCRR/CTSA UL-1 RR024153; Vascular Medicine Institute, P3HVB Grant 706654 (MVR); University of Pittsburgh Provost Technology Development Fund, Grant TDF OTM 10024 (MVR), and Clinical Trials.gov NCT 00994929.
Further Information

Publication History

Received: 30 June 2012

Accepted after major revision: 14 November 2012

Publication Date:
29 November 2017 (online)

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Summary

Desmopressin (DDAVP) is the treatment of choice in those with mild von Willebrand disease (VWD), yet 20% are unresponsive to DDAVP, and among the 80% who respond, the response is transient, as endothelial stores are depleted after three days. We, therefore, conducted a single-center Phase II clinical trial to determine safety and biologic efficacy of recombinant interleukin-11 (rhIL-11, Neumega®) in patients with VWD unresponsive or allergic to DDAVP, or mild or moderate haemophilia A (HA). Increases in VWF:RCo were observed by 48 hours after rhIL-11, with a 1.54-fold increase by Day 4, 1.30-fold in VWD and 1.73-fold in HA. Similarly, by 48 hours, increases in VIII:C were observed, with a 1.65-fold increase by Day 4, 1.86-fold in VWD and 1.48-fold in HA. Platelet VWFmRNA expression by qPCR increased 0.81-fold but did not correlate with plasma VWF:Ag responses. rhIL-11 was well tolerated, with grade 1 or less fluid retention, flushing, conjunctival erythema, except for transient grade 3 hyponatraemia in one subject after excess fluid intake for diabetic hyperglycaemia, which resolved with fluid restriction. In summary, rhIL-11 increases VWF levels in two of four DDAVP-unresponsive or allergic VWD and F.VIII levels in four of five mild or moderate haemophilia A subjects, suggesting its potential use in treatment of these disorders.