IL-11 in Adults With Von Willebrand Disease Undergoing Surgery

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 in adults with type 1 von Willebrand disease undergoing elective surgery or major dental procedure. Efficacy will be measured by estimated blood loss, and frequency and severity of bleeding and transfusion requirement during and after surgery. 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 adults with type 1 VWD undergoing elective surgery or major dental procedure. It is anticipated that 10 subjects who meet eligibility criteria will enroll and complete the study. The specific objectives are to determine the efficacy and safety or rhIL-11 during and after elective surgery, 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 Subjects With Type 1 Von Willebrand Disease Undergoing Surgery

Conditions
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Von Willebrand Disease

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females 18 years of age and older Confirmed type 1 VWD, as defined by low VWF:RCoF or low VWF:Ag and qualitatively normal VWF multimers A past bleeding history Responsive to DDAVP Scheduled elective major surgery or major dental surgery at MUH or PUH Willingness to have blood drawn 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 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 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

Sexes Eligible for Study
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All

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: Neumega (Interleukin 11, IL-11)<br>Neumega (Oprelvekin, Interleukin 11, IL-11) 25 mcg/kg subcutaneously, given for 4 days preoperatively, and on day 5 preoperatively, and for up to 2 days postoperatively | Drug: Neumega (Oprelvekin, Interleukin 11, IL-11)<br>* 25 micrograms/kg by subcutaneous injection once daily for four days, followed by once daily on days 1-3 before and after elective surgery or dental procedure<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Volume of Surgical Blood Loss | Hemostatic efficacy was measured by estimated blood loss (cc) during the surgical procedure. | 4 weeks | 
| Volume of Blood Transfusion | The volume of blood transfusion required (units of blood) after the surgical procedure. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| No. of Subjects With Detectable VWFmRNA (Von Willebrand Factor Messenger RNA). | The number of subjects with detectable VWFmRNA. | 4 weeks per subject | 
| Number of Subjects Who Experienced Adverse Events | mild headache, nausea | The time frame is within 4 weeks of surgery. | 

 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, surgery