Clinical trial NCT00524342: IL-11 in Women With Von Willebrand Disease and Refractory Menorrhagia
Official title: Phase II Clinical Efficacy Trial of Recombinant Interleukin-11 (rhIL-11, Neumega) in Women With Type 1 Von Willebrand Disease and Refractory Menorrhagia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Von Willebrand Disease
Keywords: IL-11
von Willebrand disease
von Willebrand factor
VWFmRNA
menorrhagia
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: University of North Carolina
name: Wyeth is now a wholly owned subsidiary of Pfizer
First posted: 2007-09-03
Enrollment: 7
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to determine the efficacy and safety of rhIL-11, when given subcutaneously for six consecutive months, in reducing menstrual blood loss in women with type 1 von Willebrand disease and refractory menorrhagia. Efficacy will be measured by subjective bleeding severity scale and pictorial bleeding chart. Safety will be measured by the frequency of adverse events, including fever, headache, fatigue, myalgias, arthralgias, fluid retention, or edema.

Detailed description: This study is a prospective, single-center Phase II trial of Neumega (rhIL-11) in women with type 1 VWD and menorrhagia refractory to estrogen, hormones, or hemostatic agents. It is anticipated that 10 subjects who meet eligibility criteria will enroll and complete this study. All aspects of this study, including the rhIL-11 injections and the screening, hemostatic and safety monitoring, and coagulation testing, are considered experimental. The specific objectives are to determine the efficacy and safety of rhIL-11 in reducing menstrual blood loss in adult women with type 1 VWD during six consecutive menstrual cycles, and to determine the mechanism of the hemostatic response of rhIL-11.

Eligibility criteria: Inclusion Criteria:

* Females 18-45 years of age
* Confirmed type 1 VWD, as defined by low VWF:RCoF or low VWF:Ag and qualitatively normal VWF multimers
* Menorrhagia refractory to estrogens, hormones, hemostatic agents
* Willingness to have blood drawn

Exclusion Criteria:

* Use of immunomodulatory or experimental drugs, or diuretics
* Pregnant or lactating women or those unwilling to use contraception during study
* Previous 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 substantial quantities of FVIII and/or VWF within five days of study

Primary outcomes:
measure: >50% Reduction in PBAC (Pictorial Blood Assessment Chart) at 6 Months
timeFrame: 6 months
Secondary outcomes:
measure: No. of Subjects With Detectable VWF mRNA (Von Willebrand Factor Messenger RNA).
timeFrame: The time frame is up to 7 months per subject.
measure: No. of Subjects With IL-11 Associated Adverse Events.
timeFrame: The time frame is up to 7 months per subject.
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: Hemophilia Center of Western PA
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh Medical Center
name: Margaret V. Ragni, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jankowitz RC, Nichols TC, Ragni MV. Recombinant IL-11 (Neumega, rhIL-11) increases plasma Von Willebrand Factor in Type 1 Von Willebrand Disease. Blood 108: 1003, 2006 (abstract).
citation: 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.
citation: Ragni MV, Jankowitz RC, Jaworski K, Merricks EP, Kloos MT, Nichols TC. Phase II prospective open-label trial of recombinant interleukin-11 in women with mild von Willebrand disease and refractory menorrhagia. Thromb Haemost. 2011 Oct;106(4):641-5. doi: 10.1160/TH11-04-0274. Epub 2011 Aug 11.