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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase II Clinical Efficacy Trial of Recombinant Interleukin-11 (rhIL-11, Neumega) in Women With Type 1 Von Willebrand Disease and Refractory Menorrhagia

Conditions
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Von Willebrand Disease

Intervention / Treatment
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* Drug: Oprelvekin, Interleukin 11, IL-11


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oprelvekin, Interleukin 11, IL-11<br>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 | Drug: Oprelvekin, Interleukin 11, IL-11<br>* 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<br>* Other names: Neumega (Oprelvekin, Interleukin 11, IL-11);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| >50% Reduction in PBAC (Pictorial Blood Assessment Chart) at 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. | 6 months | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IL-11, von Willebrand disease, von Willebrand factor, VWFmRNA, menorrhagia