Efficacy and Safety of IL-11 in DDAVP Unresponsive
Information source: University of Pittsburgh
Information obtained from ClinicalTrials.gov on December 08, 2011
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Hemophilia A; Von Willebrand Disease
Intervention: Neumega (Oprelvekin, Interleukin 11, IL-11) (Biological)
Phase: Phase 2
Status: Recruiting
Sponsored by: University of Pittsburgh Official(s) and/or principal investigator(s):
Margaret V. Ragni, MD, MPH, Principal Investigator, Affiliation: University of Pittsburgh
Overall contact:
Margaret V. Ragni, MD, MPH, Phone: (412) 209-7288, Email: ragni@dom.pitt.edu
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.
Clinical Details
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 design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Biologic effects by coagulation tests.
Secondary outcome: The frequency of adverse events.The mechanism of study drug effect by VWF mRNA.
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
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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.
Locations and Contacts
Margaret V. Ragni, MD, MPH, Phone: (412) 209-7288, Email: ragni@dom.pitt.edu
University of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States; Recruiting
Margaret V Ragni, MD, MPH, Phone: 412-209-7288, Email: ragni@dom.pitt.edu
Kristen Jaworski, BSN, RN, Phone: 412-209-7411, Email: kjaworski@itxm.org
Margaret V Ragni, MD, MPH, Principal Investigator
Additional Information
Related 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. Epub 2008 Aug 1.
Starting date: January 2010
Last updated: July 25, 2011
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