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Efficacy and Safety of IL-11 in DDAVP Unresponsive (IL-11DDAVP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00994929
Recruitment Status : Completed
First Posted : October 14, 2009
Results First Posted : March 2, 2016
Last Update Posted : March 2, 2016
Information provided by (Responsible Party):
Margaret Ragni, University of Pittsburgh

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Hemophilia A Von Willebrand Disease Biological: Neumega (Oprelvekin, Interleukin 11, IL-11) Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : January 2010
Actual Primary Completion Date : April 2012
Actual Study Completion Date : April 2012

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
Biological: Neumega (Oprelvekin, Interleukin 11, IL-11)
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:
  • Interleukin-11
  • IL-11
  • Oprelvekin

Primary Outcome Measures :
  1. Biologic Effects by Coagulation Tests [ Time Frame: within 4 days of study drug. ]
    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

Secondary Outcome Measures :
  1. The Frequency of Adverse Events [ Time Frame: within 11 days of study drug ]
  2. The Mechanism of Study Drug Effect by VWF mRNA. [ Time Frame: within 11 days of study drug. ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00994929

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United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
University of Pittsburgh
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Principal Investigator: Margaret V. Ragni, MD, MPH University of Pittsburgh

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Margaret Ragni, Laurel Yasko, University of Pittsburgh Identifier: NCT00994929     History of Changes
Other Study ID Numbers: PRO08070154, Wyeth 3067K1-2214
First Posted: October 14, 2009    Key Record Dates
Results First Posted: March 2, 2016
Last Update Posted: March 2, 2016
Last Verified: February 2016
Keywords provided by Margaret Ragni, University of Pittsburgh:
biologic effects
von Willebrand disease
Additional relevant MeSH terms:
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Hemophilia A
Von Willebrand Diseases
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Blood Platelet Disorders
Deamino Arginine Vasopressin
Antidiuretic Agents
Natriuretic Agents
Physiological Effects of Drugs
Antineoplastic Agents