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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Margaret Ragni, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT00994929
First received: October 12, 2009
Last updated: August 5, 2012
Last verified: August 2012
  Purpose

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 Intervention Phase
Hemophilia A
Von Willebrand Disease
Biological: Neumega (Oprelvekin, Interleukin 11, IL-11)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • Biologic effects by coagulation tests. [ Time Frame: within 4 days of study drug. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The frequency of adverse events. [ Time Frame: within 11 days of study drug. ] [ Designated as safety issue: Yes ]
  • The mechanism of study drug effect by VWF mRNA. [ Time Frame: within 11 days of study drug. ] [ Designated as safety issue: No ]

Enrollment: 9
Study Start Date: January 2010
Study Completion Date: April 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00994929

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

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Margaret Ragni, Laurel Yasko, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT00994929     History of Changes
Other Study ID Numbers: PRO08070154, Wyeth 3067K1-2214
Study First Received: October 12, 2009
Last Updated: August 5, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Pittsburgh:
biologic effects
von Willebrand disease
hemophilia
interleukin-11
DDAVp

Additional relevant MeSH terms:
Von Willebrand Diseases
Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Blood Platelet Disorders
Deamino Arginine Vasopressin
Oprelvekin
Antidiuretic Agents
Natriuretic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Hemostatics
Coagulants
Hematologic Agents
Therapeutic Uses
Cardiovascular Agents
Antineoplastic Agents

ClinicalTrials.gov processed this record on April 17, 2014