Von Willebrand Disease
Conditions
Keywords
IL-11, von Willebrand disease, von Willebrand factor, VWFmRNA, menorrhagia
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.
Interventions
DRUGOprelvekin, 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
Sponsors
University of North Carolina
Wyeth is now a wholly owned subsidiary of Pfizer
Margaret Ragni
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| >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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| IL-11 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 | 7 |
| Total | 7 |
Baseline characteristics
| Characteristic | IL-11 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants |
| Region of Enrollment United States | 7 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 7 / 7 |
| serious Total, serious adverse events | 0 / 7 |
Outcome results
Primary
>50% Reduction in PBAC (Pictorial Blood Assessment Chart) at 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.
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IL-11 | >50% Reduction in PBAC (Pictorial Blood Assessment Chart) at 6 Months | 71 percentage of participants |
Secondary
No. of Subjects With Detectable VWF mRNA (Von Willebrand Factor Messenger RNA).
No. of subjects with detectable VWFmRNA, a measure of IL-11 (interleukin-11) function, specifically increasing VWF synthesis.
Time frame: The time frame is up to 7 months per subject.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IL-11 | No. of Subjects With Detectable VWF mRNA (Von Willebrand Factor Messenger RNA). | 7 participants |
Secondary
No. of Subjects With IL-11 Associated Adverse Events.
The number of subjects with IL-11 associated adverse events.
Time frame: The time frame is up to 7 months per subject.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IL-11 | No. of Subjects With IL-11 Associated Adverse Events. | fluid retention | 6 participants |
| IL-11 | No. of Subjects With IL-11 Associated Adverse Events. | injection site bruising | 6 participants |
| IL-11 | No. of Subjects With IL-11 Associated Adverse Events. | flushing | 3 participants |