IL-11 in Women With Von Willebrand Disease and Refractory Menorrhagia

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.

• Oprelvekin, Interleukin 11, IL-11 (Drug), also known as Neumega (Oprelvekin, Interleukin 11, IL-11): 25 micrograms/kg by subcutaneous injection once daily for four days, then once daily on day 1-7 during each of six consecutive menstrual cycles

Primary outcomes

• >50% Reduction in PBAC (Pictorial Blood Assessment Chart) at 6 Months [6 months]: Subjective estimate of blood loss was measured by using a Pictorial blood assessment chart (PBAC) . The PBAC measures scores on a scale where 0 to 100 is normal and greater than 100-200 are abnormal.

Secondary outcomes

• No. of Subjects With Detectable VWF mRNA (Von Willebrand Factor Messenger RNA). [The time frame is up to 7 months per subject.]: No. of subjects with detectable VWFmRNA, a measure of IL-11 (interleukin-11) function, specifically increasing VWF synthesis.
• No. of Subjects With IL-11 Associated Adverse Events. [The time frame is up to 7 months per subject.]: The number of subjects with IL-11 associated adverse events.

Sex: Female, ages: 18 Years to 45 Years

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

Participant flow

Outcome results

• >50% Reduction in PBAC (Pictorial Blood Assessment Chart) at 6 Months (Primary), Number, percentage of participants: IL-11 71
• No. of Subjects With Detectable VWF mRNA (Von Willebrand Factor Messenger RNA). (Secondary), Number, participants: IL-11 7
• No. of Subjects With IL-11 Associated Adverse Events. (Secondary), Number, participants: IL-11 6

Adverse events

Time frame: up to 7 months

Other adverse events by term

• 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).
• 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. PMID 18680527
• Results publication: 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. PMID 21833452

• Margaret V. Ragni, MD, MPH, Principal investigator, University of Pittsburgh Medical Center