- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00994929
Efficacy and Safety of IL-11 in DDAVP Unresponsive (IL-11DDAVP)
February 3, 2016 updated by: Margaret Ragni, University of Pittsburgh
Phase II Biologic Effects Study of Recombinant Interleukin-11 (rhIL-11, Neumega) in Subjects With Moderate or Mild Hemophilia A, or Von Willebrand Disease Unable to Use DDAVP
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Interventional
Enrollment (Actual)
9
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15213
- University of Pittsburgh
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Neumega (Oprelveken, Interleukin 11)
Neumega (Oprelveken, interleukin-11 (IL-11) 25 microgram/kilogram by subcutaneou injection once daily for four days, followed on day 4 DDAVP 0.3 microgram/kilogram intravenously 30 minutes after neumega
|
25 microgram/kg IL-11 by subcutaneous injection once daily for four days, followed by DDAVP 0.3 microgram/kg by intravenous infusion over 30 minutes on day 4, 30 minutes after IL-11.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Biologic Effects by Coagulation Tests
Time Frame: within 4 days of study drug.
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VWF activity was measured by ristocetin-induced platelet agglutination using a Chronolog aggregometer11-14 and VWF:Ag by "sandwich" ELISA, using anti-VWF antibodies (DakoA082, Carpintera CA).
Results were expressed in percent, with normal human plasma pool designated 100%, and severe type 3 VWD plasma used as the negative control
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within 4 days of study drug.
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
The Frequency of Adverse Events
Time Frame: within 11 days of study drug
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within 11 days of study drug
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The Mechanism of Study Drug Effect by VWF mRNA.
Time Frame: within 11 days of study drug.
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within 11 days of study drug.
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Margaret V. Ragni, MD, MPH, University of Pittsburgh
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Ragni MV, Jankowitz RC, Chapman HL, Merricks EP, Kloos MT, Dillow AM, Nichols TC. A phase II prospective open-label escalating dose trial of recombinant interleukin-11 in mild von Willebrand disease. Haemophilia. 2008 Sep;14(5):968-77. doi: 10.1111/j.1365-2516.2008.01827.x. Epub 2008 Aug 1.
- Ragni MV, Novelli EM, Murshed A, Merricks EP, Kloos MT, Nichols TC. Phase II prospective open-label trial of recombinant interleukin-11 in desmopressin-unresponsive von Willebrand disease and mild or moderate haemophilia A. Thromb Haemost. 2013 Feb;109(2):248-54. doi: 10.1160/TH12-06-0447. Epub 2012 Dec 13.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
January 1, 2010
Primary Completion (Actual)
April 1, 2012
Study Completion (Actual)
April 1, 2012
Study Registration Dates
First Submitted
October 12, 2009
First Submitted That Met QC Criteria
October 13, 2009
First Posted (Estimate)
October 14, 2009
Study Record Updates
Last Update Posted (Estimate)
March 2, 2016
Last Update Submitted That Met QC Criteria
February 3, 2016
Last Verified
February 1, 2016
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- PRO08070154, Wyeth 3067K1-2214
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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