A Multicenter, Prospective, Open-label, Clinical Study to Assess the Effect of Using a New Risk Score Approach to Select the Most Appropriate Prophylaxis Regimen for Reaching a Favorable Outcome, When Hemophilia A Patients Switch From Standard Half-life Products to Damoctocog Alfa Pegol (Jivi)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 21
- 试验地点
- 12
- 主要终点
- Overall Number of Participants With Favorable Outcome on the Score-assigned Prophylaxis Regimen
研究概览
简要总结
Researchers are looking for a better way to treat people who have hemophilia A. Hemophilia A is a genetic bleeding disorder that is caused by the lack of a protein in the blood called "clotting factor 8" (FVIII). FVIII is naturally found in the blood where it causes the blood to clump together to help prevent and stop bleeding. People with lower levels of FVIII or with FVIII that does not work properly may bleed for a long time from minor wounds, have painful bleeding into joints, or have internal bleeding.
The study treatment, Jivi (also called damoctocog alfa pegol), is already available for doctors to prescribe to people with hemophilia A to treat and prevent bleeding. It works by replacing the missing FVIII, or the FVIII that does not work properly.
People with hemophilia A need frequent injections of FVIII products into the vein. So called standard half-life (SHL) products need to be given 2 to 4 times a week for the prevention of bleeding. In recent years, new products like Jivi called extended half-life (EHL) products have become available. These products last longer in the body so that they require to be given less often with injections every 3-5 days. Thus, these treatments may be easier and more comfortable to stick to in daily life. There is no general plan concerning the best amount of treatment and the frequency of injections for the prevention of bleeding, since the severity may be different and individual risk factors have to be considered. Doctors often decide on a treatment plan based on their experience.
The main purpose of this study is to learn how well a new scoring approach works to select a treatment plan for the prevention of bleeding in people with hemophilia A who switch their treatment from SHL products to Jivi. Different types of information are used to calculate the risk score like bleeding history, certain biological factors, and physical activity of the participant.
All participants will receive Jivi for 6 months.
In the first four weeks, all participants will receive Jivi 2 times a week at a dose level of 40 IU per kilogram body weight (also known as 40 IU/kg/dose, recommended maximum dose is 6,000 IU). Then, based on their risk score, each participant will be assigned to one of three treatment plans:
- participants with a high risk remain on Jivi administration 2 times a week at 40 IU/kg/dose
- participants with a medium risk will switch to Jivi administration every 5 days at 50 IU/kg/dose
- participants with a low risk will switch to Jivi administration every 5 days at 50 IU/kg/dose and after 4 weeks to a less frequent administration (e.g., every 7 days) at 60 IU/kg/dose To check how well the new scoring approach works for choosing the right treatment plan, researchers will look at how many participants have a favourable outcome.
This means that the participant has either fewer bleeding events vs. the pre-study treatment and takes Jivi less often or as often as the previous SHL treatment but with fewer bleeding events, or that the participant has a comparable number of bleeding events but needs to take Jivi less often than the previous treatment. Each participant will be in the study for approximately 7.5 months. During this time, 4 visits to the study site and 3 phone calls are planned. During the study, the doctors and their study team will: • do physical examinations • take blood samples • ask the participants questions about how they are feeling and what adverse events they are having. In addition, participants or their guardians are required to write down the dates of Jivi treatments and bleeding events in an electronic diary and to fill in different questionnaires on their quality of life, health status, work/ school productivity, pain, and treatment satisfaction. In addition, participants are expected to keep appointments for visits and to adhere to the assigned treatment regimen.
An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events that happen in studies, even if they do not think the adverse events might be related to the study treatments.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must be ≥ 12 years of age inclusive, at the time of signing the informed consent/assent.
- •Previously treated patients (≥ 150 EDs) with congenital hemophilia A.
- •Prophylaxis with any SHL FVIII product with a stable frequency for at least 6 consecutive months within the last 12 months prior to screening before entering the study and documented in medical records. Stable frequency is defined as a minimum 18 weeks of treatment in a 6 (consecutive) calendar month period in the 12 months prior to screening. Patients can be on any non-Jivi EHL between the 6-month stable SHL prophylaxis period and start of study treatment.
- •Documented bleeding rate (ABR) while on stable frequency SHL prophylaxis for at least 6 consecutive months within the last 12 months prior to screening.
- •No current evidence (≥ 0.6 BU/mL) of FVIII inhibitors. If a participant has had a positive inhibitor titer in the past (≥ 0.6 BU/mL on two occasions) but has been tolerized for at least 1 year since the last positive titer with at least 1 negative inhibitor assay test during that period, they can be enrolled. If a participant has had a positive inhibitor titer in the past (≥ 0.6 BU/mL) but did not require tolerization and has had at least 1 negative inhibitor assay test during a minimum period of at least 1 year since the last positive titer, they can be enrolled.
- •If they are human immunodeficiency virus (HIV) positive, cluster of differentiation 4 (CD4+) lymphocyte count should be > 200/mm^3 within 1 year before entering the study and documented in medical records. -
- •Participants who are willing to complete an electronic diary (eDiary).
- •Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- •For adolescent participants (≥ 12 to < 18 years), a legal guardian must be available to help the study-site personnel ensure follow-up; accompany the participant to the study site on each assessment day according to the Schedule of Activities (SoA) (e.g. able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures); consistently and consecutively be available to provide information on the participant using the PROs during the scheduled study visits; accurately and reliably dispense study intervention as directed.
- •For adolescent participants, a legal guardian must be able to accurately maintain the child's take-home record, including items of general health.
排除标准
- •Any other inherited or acquired bleeding disorder in addition to hemophilia A. Note: von Willebrand disease should be diagnosed per local clinical practice. Participants with a diagnosis of von Willebrand disease in medical records or diagnosed at the time of screening will be excluded.
- •Platelet count < 100,000/mm^3
- •Evidence of inhibitor to FVIII (≥ 0.6 BU/mL) within the last 1 year
- •The participant is currently participating in another investigational drug study or has participated in a clinical study involving an investigational drug or device within 30 days of signing informed consent.
- •The participant has a planned major surgery.
- •Documentation of missing risk score parameters other than physical activity .
- •Known hypersensitivity to the drug substance, excipients, or mouse or hamster protein.
- •Any other significant medical condition that the investigator feels would be a risk to the participant or would impede the study.
- •Close affiliation with the investigational site; e.g. a close relative of the investigator, dependent person (e.g. employee or student of the investigational site).
- •Otherwise vulnerable participants (e.g. participants who are in custody by order of an authority).
- •Judgment by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures (i.e. eDiary completion, clinic visits, phone updates), restrictions, and requirements.
研究组 & 干预措施
Damoctocog alfa-pegol prophylaxis regimens
Prophylaxis regimens: All participants will begin with prophylaxis 2x/week (40 IU/kg/dose (recommended maximum dose 6,000 IU)) Participants with a high risk score (> 4) continue on prophylaxis 2x/week (40 IU/kg/dose). Participants with a medium risk score (2 to 4) will switch after 4 weeks to prophylaxis Q5D (50 IU/kg/dose). Participants with a low risk score (< 2) will switch after 4 weeks to prophylaxis Q5D (50 IU/kg/dose) and then after 4 weeks to a less frequent (e.g. Q7D) regimen (60 IU/kg/dose).
干预措施: Damoctocog alfa-pegol is a recombinant B-domain deleted human coagulation FVIII variant site specifically conjugated with a 60 kDa, branched (30 kDa each) polyethylene glycol (PEG). (Biological)
结局指标
主要结局
Overall Number of Participants With Favorable Outcome on the Score-assigned Prophylaxis Regimen
时间窗: up to 6 months
Overall number of participants with favorable outcomes after prophylaxis regimen assignment by a risk score, based on a participant's baseline phenotypic and biologic variables, when switching from a standard half-life (SHL) product to Jivi.
次要结局
- Annualized Bleeding Rate (ABR) (Total, Joint, Spontaneous)(up to 6 months)
- Change in Total ABR From Pre-study(up to 6 months)
- Change in the Frequency of Pre-study SHL Teratment to the Frequency of Jivi Administration (Infusions/Month)(up to 6 months)
- Occurrence of Participants With 0 and ≤ 1 Spontaneous Bleeds(up to 6 months)
- Change in Haemophilia Quality of Life Questionnaire (Haem-A-QoL or Haemo-QoL)(up to 6 months)
- Patient's Global Impression of Change (PGI-C)(up to 6 months)
- EuroQoL 5 Dimensions (EQ-5D-5L) Questionnaire(up to 6 months)
- Treatment Satisfaction Questionnaire for Medication (TSQM)(up to 6 months)
- Work Productivity and Activity Impairment (WPAI) Questionnaire Scores(up to 6 months)
- Number of Target Joints and Change in Target Joint Status From Baseline(up to 6 months)