Phase II Study of IL-11 (Neumega) in Von Willebrand Disease

Study Overview
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Brief Summary
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This study is testing the use of rhIL-11 (recombinant interleukin 11, Neumega) in individuals with Von Willebrand disease. The purpose is to evaluate: if rhIL-11 corrects VWF (Von Willebrand Factor) levels to normal if rhIL-11 and DDAVP together will boost VWF levels even higher the onset, peak, and duration of rhIL-11 effect if rhIL-11 is safe in individuals with Von Willebrand Disease

Detailed Description
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This is a prospective, single center, open-label, escalating dose Phase II comparison study of interleukin-11 (rhIL-11, Neumega) in subjects with type 1 Von Willebrand Disease (VWD). The purpose is to establish the clinical safety and hemostatic efficacy of rhIL-11 in individuals with type 1 Von Willebrand disease. Study subjects will include the following subjects: age >= 18 years of age diagnosis of VWD confirmed by: 2a) at least 2 of 4 abnormal vWD-related coagulation tests; 2b) a past bleeding history A total of 10-16 subjects are anticipated to be enrolled and complete the study. The specific aims of the study are: to compare the hemostatic efficacy of three escalating doses of rhIL-11 to determine the biologic effects of rhIL-11 to determine whether DDAVP, when given after the seventh daily dose of rhIL-11, enhances hemostatic efficacy or rhIL-11 to compare the safety of three escalating doses of rhIL-11 Efficacy will be based on the number and percent increase of VWD-related coagulation tests into the normal range, or at least to 2-3 times baseline. Safety will be based on the number and frequency of adverse reactions, including fever, headache, fatigue, arthralgias, myalgias, fluid retention, and edema. The study will last up to 4 weeks per subject, and for 24 months for the entire study.

Official Title
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Phase II Comparison Study of Hemostatic Efficacy of Escalating Doses of Interleukin-11 (rhIL-11, Neumega) in Subjects With Type 1 Von Willebrand Disease

Conditions
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Von Willebrand Disease

Intervention / Treatment
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* Drug: recombinant interleukin-11
* Drug: recombinant interleukin-11
* Drug: recombinant interleukin-11


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females 18 years of age or older Confirmed VWD by 2 of 4 VWD coagulation tests abnormal A past bleeding history No hormone, oral contraceptive, estrogen use in past 8 weeks Willingness to have blood drawn Willingness to sign informed consent Exclusion Criteria: Presence of other bleeding disorder, e.g. acquired VWD, thrombocytopenia Use of estrogens, hormones, oral contraceptives in past 8 weeks Use of immunomodulatory or experimental drugs or diuretics Pregnant or lactating women Past 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 FVIII, VWF within 5 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: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>rhIL-11 (Interleukin-11, Neumega) 25 mcg/kg subcutaneously daily for 7 days | Drug: recombinant interleukin-11<br>* 25 mcg/kg subcutaneously daily for seven days<br>* Other names: rhIL-11, Neumega;|
| Experimental: B<br>rhIL-11 (interleukin-11, Neumega) 50 mcg/kg subcutaneously daily for 7 days | Drug: recombinant interleukin-11<br>* 50 mcg/kg subcutaneously daily for 7 days<br>* Other names: rhIL-11, Neumega;|
| Experimental: C<br>rhIL-11 (Interleukin-11, Neumega) 10 mg/kg subcutaneously daily for 7 days | Drug: recombinant interleukin-11<br>* 10 mcg/kg subcutaneously daily for 7 days<br>* Other names: rhIL-11, Neumega;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number and percent increase of VWD coagulation tests after seven daily doses of rhIL-11, boosted by DDAVP day 7. |  | The time frame is up to 14 days per subject. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number and frequency of IL-11 associated adverse events. |  | The time frame is up to 14 days per subject. | 
| The mechanism of IL-11 biologic effect by VWFmRNA. |  | The time frame is within 14 days per subject. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Von Willebrand Disease, Bleeding, Coagulation, Hemostatic agent