IL-11 in Women With Von Willebrand Disease and Refractory Menorrhagia

Phase 2

Completed

Brief Summary: The purpose of this study is to determine the efficacy and safety of rhIL-11, when given subcutaneously for six consecutive months, in reducing menstrual blood loss in women with type 1 von Willebrand disease and refractory menorrhagia. Efficacy will be measured by subjective bleeding severity scale and pictorial bleeding chart. Safety will be measured by the frequency of adverse events, including fever, headache, fatigue, myalgias, arthralgias, fluid retention, or edema.

Detailed Description: This study is a prospective, single-center Phase II trial of Neumega (rhIL-11) in women with type 1 VWD and menorrhagia refractory to estrogen, hormones, or hemostatic agents. It is anticipated that 10 subjects who meet eligibility criteria will enroll and complete this study. All aspects of this study, including the rhIL-11 injections and the screening, hemostatic and safety monitoring, and coagulation testing, are considered experimental. The specific objectives are to determine the efficacy and safety of rhIL-11 in reducing menstrual blood loss in adult women with type 1 VWD during six consecutive menstrual cycles, and to determine the mechanism of the hemostatic response of rhIL-11.

Recruitment & Eligibility

Inclusion Criteria

Females 18-45 years of age
Confirmed type 1 VWD, as defined by low VWF:RCoF or low VWF:Ag and qualitatively normal VWF multimers
Menorrhagia refractory to estrogens, hormones, hemostatic agents
Willingness to have blood drawn

Exclusion Criteria

Use of immunomodulatory or experimental drugs, or diuretics
Pregnant or lactating women or those unwilling to use contraception during study
Previous cardiac disease, congestive failure, arrhythmia (e.g., atrial fibrillation, atrial flutter), hypertension, MI, stroke, or thrombosis
Past allergic reaction to Neumega or DDAVP
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

Arm && Interventions

Group	Intervention	Description
Oprelvekin, Interleukin 11, IL-11	Oprelvekin, Interleukin 11, IL-11	25 micrograms/kg by subcutaneous injection once daily for four days, then once daily on day 1-7 during each of six consecutive menstrual cycles

Primary Outcome Measures

Name	Time	Method
>50% Reduction in PBAC (Pictorial Blood Assessment Chart) at 6 Months	6 months	Subjective estimate of blood loss was measured by using a Pictorial blood assessment chart (PBAC) . The PBAC measures scores on a scale where 0 to 100 is normal and greater than 100-200 are abnormal.

Secondary Outcome Measures

Name	Time	Method
No. of Subjects With IL-11 Associated Adverse Events.	The time frame is up to 7 months per subject.	The number of subjects with IL-11 associated adverse events.
No. of Subjects With Detectable VWF mRNA (Von Willebrand Factor Messenger RNA).	The time frame is up to 7 months per subject.	No. of subjects with detectable VWFmRNA, a measure of IL-11 (interleukin-11) function, specifically increasing VWF synthesis.