A Feasibility Trial Using Extended Half Life Factor Products in the Reduction of Menstrual Bleeding in Symptomatic Hemophilia A and B Carriers
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Reduction in menstrual bleeding measured by the Pictorial Bleeding Assessment Chart (PBAC).
研究概览
简要总结
The purpose of this feasibility study is to find out if two clotting factor products, Eloctate [hemophilia A] and Alprolix [hemophilia B], can reduce the amount of menstrual bleeding in female hemophilia A and B carriers (14 years of age or older) who have severe or heavy bleeding. These products are FDA-approved for use in males with hemophilia A and B to prevent and treat bleeding. They are not approved specifically to reduce menstrual bleeding, but may be useful for this purpose. Both products have an "extended half life" which means they circulate in the body longer than other FVIII or FIX products. The study team will gather additional information about the safety of these drugs and how well they work. The results of this feasibility study will provide information for an upcoming larger study.
详细描述
Hemophilia A or B is caused by defects in the factor VIII or IX gene, respectively, of which is located on the X chromosome. This disorder exhibits X-linked inheritance, in which primarily males, with a single X chromosome, are affected and females, with two X chromosomes, are heterozygotes, or carriers. Hemophilia carriers show a wide distribution of factor VIII or IX levels with a mean of 50%, which overlaps the distribution of non-carrier women.
Heavy menstrual bleeding is defined as menstrual bleeding that lasts more than 7 days or more specifically as the loss of more than 80cc of blood per cycle. Management is critical as it can lead to iron deficiency anemia, lead to school absence and affects the general quality of life. There are multiple options to control or reduce menstrual bleeding in hemophilia A and B carriers, they include but not limited to the following options: Antifibrinolytics (Aminocaproic acid, Tranexamic acid), Synthetic desmopressin (DDAVP, SQ or IN) or hormonal therapies (Combined oral contraceptives, Progestin only options, IUD, etc).
The use of recombinant factor replacement has been poorly studied and limited by a relatively short half-life in relation to the typical length of a menstrual period. The purpose of this feasibility study is to find out if two clotting factor products, Eloctate [hemophilia A] and Alprolix [hemophilia B], can reduce the amount of menstrual bleeding in female hemophilia A and B carriers (14 years of age or older) who have severe or heavy bleeding. These products are FDA-approved for use in males with hemophilia A and B to prevent and treat bleeding. They are not approved specifically to reduce menstrual bleeding, but may be useful for this purpose. Both products have an "extended half life" which means they circulate in the body longer than other FVIII or FIX products. The study team will gather additional information about the safety of these drugs and how well they work. Five out of the 16 anticipated enrolled patients will be approach to request participation in the exploratory aim in which the subject is taught to perform a hemoglobin check (CBC) every other day using a novel point of care device (Anemocheck) during 2 consecutive menstrual cycles. In addition, they will have CBCs drawn within 4-6 hours for comparison and correlation. The study team will also correlate symptoms of heavy menstrual bleeding with a 2grams drop in the hemoglobin. All the results of this study will provide information for an upcoming larger study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 14 Years 至 55 Years（Child, Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Females of reproductive age who experience monthly menstrual bleedings
- •Female Hemophilia A or B carrier (heterozygote, lyonized or Turner's Syndrome)
- •FVIII or FIX activity ≤60% at time of the study
- •Baseline Pictorial Bleeding Assessment Chart >150 mean at time of recruitment
- •Negative pregnancy test at time of enrollment
- •Both female and her male partner have agreed to use an acceptable barrier method of birth control (e.g., diaphragm, cervical cap, male condom, female condom, and spermicidal foam, sponges, and film) throughout the duration of this study (for sexually active participants)
排除标准
- •Has not reached menarche
- •Menopause: natural or induced by surgical/medical treatment
- •Pregnant or breasfeeding
- •Female or her male partner refuses to use barrier method of birth control (for sexually active)
- •Current use of any of the following contraceptives (copper IUD, oral combined, Progestin-only including but not limited to: Provera, Aygestin, Nexplanon, Implanon, Depo Provera, Mirena IUD)
- •VWF:Ag or VWF:RCo <40%
- •Diagnosis of a qualitative platelet disorder
- •Personal history of thrombosis or superficial thrombosis
- •First degree relative with a history of thrombosis
- •Personal history of concomitant bleeding or clotting disorder
- •Cigarette smoker
- •Willing to avoid taking an anti-fibrinolytic agent (amicar, transexamic acid, lysteda) during the trial
研究组 & 干预措施
Hemophilia A symptomatic female carriers
Hemophilia A symptomatic female carriers with a baseline FVIII activity of ≤60% receive recombinant FVIII Fc fusion product Eloctate.
Some of participants will be taught to perform a hemoglobin check using a patient-operated diagnostic device for anemia AnemoCheck every other day during 2 consecutive menstrual cycles.
干预措施: Recombinant FVIII Fc fusion product Eloctate (Drug)
Hemophilia A symptomatic female carriers
Hemophilia A symptomatic female carriers with a baseline FVIII activity of ≤60% receive recombinant FVIII Fc fusion product Eloctate.
Some of participants will be taught to perform a hemoglobin check using a patient-operated diagnostic device for anemia AnemoCheck every other day during 2 consecutive menstrual cycles.
干预措施: Patient-operated diagnostic device for anemia AnemoCheck. (Device)
Hemophilia B symptomatic female carriers
Hemophilia B symptomatic female carriers with a baseline FIX activity of ≤60% receive recombinant FIX Fc fusion product Alprolix.
Some of participants will be taught to perform a hemoglobin check using a patient-operated diagnostic device for anemia AnemoCheck every other day during 2 consecutive menstrual cycles.
干预措施: Recombinant FIX Fc fusion product Alprolix (Drug)
Hemophilia B symptomatic female carriers
Hemophilia B symptomatic female carriers with a baseline FIX activity of ≤60% receive recombinant FIX Fc fusion product Alprolix.
Some of participants will be taught to perform a hemoglobin check using a patient-operated diagnostic device for anemia AnemoCheck every other day during 2 consecutive menstrual cycles.
干预措施: Patient-operated diagnostic device for anemia AnemoCheck. (Device)
结局指标
主要结局
Reduction in menstrual bleeding measured by the Pictorial Bleeding Assessment Chart (PBAC).
时间窗: Monthly throughout study duration for 7 months
Menstrual loss is tracked via paper and electronic PBAC, calculated via visual interpretation centrally and correlated to the ability of a participant to correctly assign pad or tampon saturation. The PBAC will be estimated (mean) over the three-month intervention period to assess if 30% reduction in menstrual bleeding was achieved. PBAC is a semi-quantitative, self-administered pictorial tool. The total score is calculated by adding up the sum of all scores for the tampons or pads used, with a score greater than 150 having an 86% sensitivity and 89% specificity for heavy menstrual bleeding (HMB). Possible range is dependent on quantitative and qualitative amount of bleeding during menstruation: * For tampons: 0.5-1 for lightly stained, 1-4 for moderately soiled and 4-12 for completely saturated tampons. * For pads: 1 for lightly stained, 2-6 for moderately soiled and 4-15 for completely saturated pads. * Clots were given a score of 1 for small and 5 for large clots.
次要结局
- Change in FIX level after the first dose of Alpolix.(First visit of interventional study phase (visit 4, day 90 of the study) : 15-30 min,4 hours,48 hours, and 72 hours after infusion.)
- Change in Short Form 36 (SF-36) score.(Monthly, prior to the beginning of each menstrual cycle either by phone or in person for the study duration of 7 months)
- Change in Patient-Reported Outcomes Measurement Information Systems (PROMIS-43) score.(Monthly, prior to the beginning of each menstrual cycle either by phone or in person for the study duration of 7 months.)
- Change in FVIII level after the first dose of Eloctate.(First visit of interventional study phase (visit 4, day 90 of the study) : 15-30 min, 2 hours, 4 hours, 18-24 hour after infusion.)
- Number of hypersensitivity reactions.(Througout the interventional phase of the study (visit 4-7 of the study or months 4-7))
- Accuracy of hemoglobin levels detection by Anemocheck.(Every other day during 2 consecutive menstrual cycles during non-interventional study phase (up to Day 60 of the study).)
- Change in Menorrhagia Impact Questionnaire (MIQ) score.(Monthly, prior to the beginning of each menstrual cycle either by phone or in person for the study duration of 7 months)
研究者
Robert Sidonio
Assistant Professor of Pediatrics
Emory University