Efficacy and Safety of IL-11 in DDAVP Unresponsive

This is a prospective, single center, Phase II biologic effects study of recombinant
interleukin-11 (rhIL-11, Neumega) in subjects hemophilia A, moderate or mild; or with Von
Willebrand disease unable to take desmopressin acetate (DDAVP) because they are
unresponsive, allergic, or DDAVP is contraindicated. The purpose of the study is to
establish the biologic efficacy and safety of rhIL-11 in those not able to take DDAVP. Study
subjects will include adults, age >= 18 years, with hemophilia A, moderate, defined as
factor VIII 0.01-0.04 U/ml, or mild, defined as factor VIII >= 0.05 U/ml; or with VWD
defined by low VWF:RCo and /or low VWF:Ag, past bleeding history, and/or family history of
VWD. A total of 10-16 subjects will be enrolled in order to assure that 10 complete the
study. The specific aims of the study are: 1) to determine the biologic effect of rhIL-11
when given 4 consecutive days; 2) to determine the safety of rhIL-11 when used in subjects
with hemophilia A, moderate or mild; or with VWD unresponsive or unable to take DDAVP; and
3) to determine the mechanism of the hemostatic effects of rhIL-11. The biologic efficacy
outcomes will be measured by VWD-related coagulation tests (VWF:RCo, FVIII:C, VWF:Ag,
closure times) before and after rhIL-11 injection. Safety outcomes will be measured by the
number and frequency of adverse events, including fever, headache, fatigue, myalgias,
arthralgias, fluid retention, or edema. The mechanism of rhIL-11 hemostatic effect will be
measured by VWFmRNA before and after rhIL-11 response. Response to DDAVP following rhIL-11
will also be assessed in those in whom DDAVP is not contraindicated. The study will last up
to 1 month per subject, and for 24 months for the entire study.

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.