Efficacy and Safety of IL-11 in DDAVP Unresponsive
Efficacy and Safety of IL-11 in DDAVP Unresponsive
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.
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.