Clinical trial NCT00151125: Phase II Study of IL-11 (Neumega) in Von Willebrand Disease
Official title: Phase II Comparison Study of Hemostatic Efficacy of Escalating Doses of Interleukin-11 (rhIL-11, Neumega) in Subjects With Type 1 Von Willebrand Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Von Willebrand Disease
Keywords: Von Willebrand Disease
Bleeding
Coagulation
Hemostatic agent
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: Wyeth is now a wholly owned subsidiary of Pfizer
name: University of North Carolina
First posted: 2005-09-08
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is testing the use of rhIL-11 (recombinant interleukin 11, Neumega) in individuals with Von Willebrand disease. The purpose is to evaluate:

1. if rhIL-11 corrects VWF (Von Willebrand Factor) levels to normal
2. if rhIL-11 and DDAVP together will boost VWF levels even higher
3. the onset, peak, and duration of rhIL-11 effect
4. if rhIL-11 is safe in individuals with Von Willebrand Disease

Detailed description: 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:

1. age \>= 18 years of age
2. 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:

1. to compare the hemostatic efficacy of three escalating doses of rhIL-11
2. to determine the biologic effects of rhIL-11
3. to determine whether DDAVP, when given after the seventh daily dose of rhIL-11, enhances hemostatic efficacy or rhIL-11
4. 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.

Eligibility criteria: 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

Primary outcomes:
measure: The number and percent increase of VWD coagulation tests after seven daily doses of rhIL-11, boosted by DDAVP day 7.
timeFrame: The time frame is up to 14 days per subject.
Secondary outcomes:
measure: The number and frequency of IL-11 associated adverse events.
timeFrame: The time frame is up to 14 days per subject.
measure: The mechanism of IL-11 biologic effect by VWFmRNA.
timeFrame: The time frame is within 14 days per subject.
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: Hemophilia Center of Western Pennsylvania and General Clinical Research Center
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Margaret V. Ragni, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: