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

Thromb Haemost. 2013 Feb;109(2):248-54. doi: 10.1160/TH12-06-0447. Epub 2012 Dec 13.

Abstract

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 wer e 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.

Trial registration: ClinicalTrials.gov NCT00994929.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood
  • Deamino Arginine Vasopressin / adverse effects
  • Deamino Arginine Vasopressin / therapeutic use*
  • Drug Resistance*
  • Factor VIII / metabolism
  • Female
  • Hemophilia A / blood
  • Hemophilia A / diagnosis
  • Hemophilia A / drug therapy*
  • Hemostatics / adverse effects
  • Hemostatics / therapeutic use*
  • Humans
  • Interleukin-11 / adverse effects
  • Interleukin-11 / therapeutic use*
  • Male
  • Middle Aged
  • Pennsylvania
  • Prospective Studies
  • Protein Multimerization
  • RNA, Messenger / blood
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / therapeutic use
  • Reverse Transcriptase Polymerase Chain Reaction
  • Severity of Illness Index
  • Time Factors
  • Treatment Outcome
  • Young Adult
  • von Willebrand Diseases / blood
  • von Willebrand Diseases / diagnosis
  • von Willebrand Diseases / drug therapy*
  • von Willebrand Diseases / genetics
  • von Willebrand Factor / genetics
  • von Willebrand Factor / metabolism

Substances

  • Biomarkers
  • Hemostatics
  • Interleukin-11
  • RNA, Messenger
  • Recombinant Proteins
  • von Willebrand Factor
  • F8 protein, human
  • Factor VIII
  • Deamino Arginine Vasopressin
  • oprelvekin

Associated data

  • ClinicalTrials.gov/NCT00994929