Efficacy and Safety of IL-11 in DDAVP Unresponsive
Condition: Hemophilia A; Von Willebrand Disease
MeSH terms: Hemophilia A; Von Willebrand Diseases
Intervention: Neumega (Oprelvekin, Interleukin 11, IL-11)
Intervention description: 25 microgram/kg IL-11 by subcutaneous injection once daily for four days, followed by DDAVP 0.3 microgram/kg by intravenous infusion over 30 minutes on day 4, 30 minutes after IL-11.
Intervention MeSH terms: Oprelvekin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 9.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: biologic effects; von Willebrand disease; hemophilia; interleukin-11; DDAVp

Summary:

      The purpose of this study is to determine the biologic efficacy and safety of rhIL-11 when
      given subcutaneously in adults with moderate or mild hemophilia A or Von Willebrand disease
      unresponsive to DDAVP. Biologic efficacy will be measured by the number and percent increase
      of VWD coagulation tests (FVIII:C, VWF: Ag, VWF: RCo, closure time, APTT, and VWF multimers)
      to the normal range, or at least to 1.5-3 time baseline, following dosing of rhIL-11 when
      given daily for 4 days, and boosted by DDAVP infusion on day 4, in those in whom DDAVP is not
      contraindicated. Safety will be measured by the frequency of adverse events, including fever,
      headache, fatigue, myalgias, arthralgias, fluid retention, or edema.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Males or females >= 18 years of age.

          -  A diagnosis of hemophilia A, moderate (FVIII:C 0.01-0.04 U/ml) or mild (FVIII:C >=
             0.05 U/ml); or a diagnosis of VWD, defined by a low VWF:RCo and past bleeding history.

          -  For those with VWD, an inability to use DDAVP due to i) unresponsiveness defined as
             VWF:RCo or FVIII:C level lower than 50 IU/dl or less than a 3-fold increase after 0.3
             microgram/kg DDAVP; ii) allergic reactions or seizures; or iii) a contraindication to
             DDAVP.

          -  Willingness to have blood drawn.

          -  Willingness to sign informed consent.

        Exclusion Criteria:

          -  Presence of other bleeding disorders, acquired Von Willebrand disease, primary
             thrombocytopenia.

          -  Use of immunomodulatory or experimental drugs, or diuretics.

          -  Pregnant or lactating women.

          -  Previous cardiac disease, congestive failure, arrhythmia (e.g. atrial fibrillation,
             atrial flutter), hypertension, MI, stroke, or thrombosis.

          -  Past allergic reaction to Neumega.

          -  Surgery within the past 8 weeks.

          -  Inability to comply with study protocol requirements.

          -  Concomitant use of antiplatelet drugs, anticoagulants, dextran, aspirin or NSAIDs.

          -  Treatment with DDAVP, cryoprecipitate, whole blood, plasma and plasma derivatives
             containing substantial quantities of FVIII and/or VWF within five days of study.

          -  Baseline safety and/or hematology lab values outside the normal limits and/or an EKG
             indicating an arrhythmia.