NCT05707351已完成3 期
A Phase 3, Prospective, Multicenter, Open-label Study of Efficacy, Safety, and Pharmacokinetics of PEGylated Recombinant Factor VIII (ADYNOVATE) Administered for Prophylaxis and Treatment of Bleeding in Chinese Previously Treated Patients With Severe Hemophilia A (FVIII <1%)
Takeda12 个研究点 分布在 1 个国家目标入组 37 人开始时间: 2023年3月27日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 37
- 试验地点
- 12
- 主要终点
- Total Annualized Bleeding Rates (ABR)
研究概览
简要总结
The main aim of the study is to determine how well Adynovate works to decrease bleeding in previously treated Chinese men and boys with severe hemophilia A when given prophylactically.
Participants will be treated with Adynovate twice a week for 26 weeks or until participants have received 50 days of treatment with Adynovate (whichever takes longer). Participants will need to visit their study clinic several times during their participation.
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 65 Years（Child, Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Participant and/or legally authorized representative must voluntarily sign a written informed consent form (ICF) after all relevant aspects of the study have been explained and discussed with the Participant. For the participants less than (<) 18 years old, participants will give assent AND their parents/legally authorized representative should sign the ICF accordingly.
- •Participant and/or legally authorized representative understands and is willing and able to comply with all requirements of the study protocol.
- •Participant should be ethnic Chinese.
- •Participant is 12 to 65 years of age at screening and male.
- •Participant has severe hemophilia A (FVIII clotting activity <1 percent [%]) as confirmed by the central laboratory at screening after a washout period of at least 72 to 96 hours.
- •The last on-demand or prophylactic treatment received is within 3 months before screening.
- •Participant has documented previous treatment with plasma-derived FVIII concentrates or recombinant FVIII for greater than (>) 150 EDs.
- •Participant is human immunodeficiency virus (HIV)-negative, or HIV-positive with stable disease and CD4+ count greater than or equal to (>=) 200 cells per cubic millimeter (/mm^3).
- •Participant is hepatitis C virus (HCV) negative by antibody testing (if positive, additional polymerase chain reaction testing will be performed to confirm), as confirmed at screening; or HCV-positive with chronic stable hepatitis, as assessed by the investigator.
排除标准
- •Participant has detectable FVIII inhibitory antibodies (>=0.6 Bethesda units [BU] per milliliter [/mL] using the Nijmegen modification of the Bethesda assay) as confirmed by the central laboratory at screening.
- •Participant has a confirmed history of FVIII inhibitory antibodies (>=0.6 BU using the Nijmegen modification of the Bethesda assay or >=0.6 BU using the Bethesda assay) at any time prior to screening.
- •Participant has a known hypersensitivity to Adynovate or ADVATE or any of the components of the study drugs, such as mouse or hamster proteins, or other FVIII products.
- •Participant has been diagnosed with an inherited or acquired hemostatic defect other than hemophilia A (example, qualitative platelet defect or von Willebrand's disease).
- •Participant has severe hepatic dysfunction (example, >=5 times the upper limit of normal [ULN] for alanine aminotransferase [ALT] or aspartate aminotransferase [AST], a recent or persistent international normalized ratio [INR] >1.5, as confirmed by the local laboratory at screening).
- •Participant has severe renal impairment (serum creatinine >1.5 times the ULN) as confirmed by the local laboratory at screening.
- •Participant is planned or likely to undergo major surgery during the study period.
- •Participant has current or recent (<30 days) use of other PEGylated drugs before study participation or scheduled use of such drugs during study participation.
- •Participant has received emicizumab therapy within 6 months of screening.
- •Participant is currently receiving, or scheduled to receive during the study, an immunomodulating drug (example, systemic corticosteroid agent at a dose equivalent to hydrocortisone >10 milligram per day [mg/day], or alpha-interferon) other than antiretroviral chemotherapy.
- •Participant has participated in another clinical study involving the use of an investigational product (IP) other than Adynovate or an investigational device within 30 days before the screening visit or is scheduled to participate in another clinical study involving an IP or investigational device during this study.
- •Participant has a medical, psychiatric, or cognitive illness or recreational drug/alcohol use that, in the opinion of the investigator, would affect participant safety or compliance.
- •Participant, in the opinion of the investigator, is unable or unwilling to comply with the study protocol.
研究组 & 干预措施
Adynovate 45±5 IU/kg
Experimental
Participants received prophylactic treatment with Adynovate (45 [±5] IU/kg), infusion, IV, twice weekly, for at least 50 EDs, or approximately 28 weeks.
干预措施: Adynovate (Biological)
结局指标
主要结局
Total Annualized Bleeding Rates (ABR)
时间窗: Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks)
Total ABR was defined as the number of treated and non-treated bleeding episodes (BEs) that occurred during the treatment period, calculated as, ABR= number of unique bleeds during treatment period/(length of treatment period \[days\]/365.25). Total ABR for all BEs, spontaneous or traumatic, recorded in the participant's electronic diary and/or recorded in the physician/nurse/study site notes were reported.
次要结局
- Daily Intra-Operative and Post-Operative Weight-Adjusted Consumption Dose of Adynovate(Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks))
- Number of Participants Who Required Perioperative Transfusion of Blood, Red Blood Cells, Platelets, and Other Blood Products(Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks))
- ABR Based on Bleeding Site(Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks))
- ABR Based on Bleeding Cause(Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks))
- Number of Adynovate Infusions Per Week During the Prophylactic Treatment Period(Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks))
- Number of Adynovate Infusions Per Month During the Prophylactic Treatment Period(Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks))
- Weight-adjusted Consumption of Adynovate Per Week During the Prophylactic Treatment Period(Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks))
- Weight-adjusted Consumption of Adynovate Per Month During the Prophylactic Treatment Period(Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks))
- Percentage of Participants With Zero Bleeding Episodes During the Study(Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks))
- Average Time Interval Between Bleeding Episodes (BEs)(Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks))
- Number of Bleeding Events in Each Category of Hemostatic Efficacy Rating at Resolution of Breakthrough Bleeding Episode(Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks))
- Number of Adynovate Infusions Per Bleeding Episode(Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks))
- Weight-adjusted Consumption of Adynovate Per Bleeding Episode(Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks))
- Maximum Concentration (Cmax) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate(Day -1 and Week 20: pre-infusion, post-infusion at multiple timepoints up to 96 hours)
- Number of Minor Surgeries With Hemostatic Efficacy Based on Global Hemostatic Efficacy Assessment (GHEA) Score as Assessed by the Operating Surgeon/Investigator(Baseline through study completion or ≥50 EDs whichever occurred last (approximately 28 weeks))
- Volume of Actual and Predicted Intra-operative and Post-operative Blood Loss After the Surgery as Assessed by the Operating Surgeon/Investigator(Post-operative: Day 1 and at discharge Week 26)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Treatment-emergent Adverse Events (Serious TEAEs)(Up to approximately 28 weeks)
- Number of Participants With Confirmed Inhibitory Antibodies to Factor VIII (FVIII), Binding Immunoglobulin G (IgG) and Immunoglobulin M (IgM) Antibodies to Adynovate and Chinese Hamster Ovary (CHO) Protein(Up to approximately 28 weeks)
- FVIII Activity Level in Plasma Assessed by a 1-stage Clotting Assay(Day -1 and Week 20: pre-infusion, post-infusion at multiple time-points up to 96 hours)
- Incremental Recovery Over Time During Adynovate Prophylactic Treatment(Baseline, Week 6, and Study Completion (approximately Week 28))
- Pre-dose Level of FVIII Activity in Plasma(Baseline, Weeks 2, 6, 12, and Study Completion (approximately Week 28): Within 30 minutes pre-infusion)
- Pre-dose Level of FVIII Antigen in Plasma(Baseline, Weeks 2, 6, 12, 20, and Study Completion (approximately Week 28): Within 30 minutes pre-infusion)
- Pre-dose Level of Von Willebrand Factor (VWF) Antigen in Plasma(Baseline, Weeks 2, 6, 12, 20, and Study Completion (approximately Week 28): Within 30 minutes pre-infusion)
- Clearance (CL) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate(Day -1 and Week 20: pre-infusion, post-infusion at multiple timepoints up to 96 hours)
- Volume of Distribution for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate(Day -1 and Week 20: pre-infusion, post-infusion at multiple timepoints up to 96 hours)
- Area Under the Concentration Versus Time Curve From 0 to 96 Hours (AUC0-96) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate(Day -1 and Week 20: pre-infusion, post-infusion at multiple timepoints up to 96 hours)
- Pre-dose Concentration (Cpredose) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate(Day -1 and Week 20: pre-infusion, post-infusion at multiple timepoints up to 96 hours)
- Terminal Phase Elimination Half-life (T1/2) for FVIII Activity Following an Initial Single Dose and Steady-state Dose of Adynovate(Day -1 and Week 20: pre-infusion, post-infusion at multiple timepoints up to 96 hours)
研究者
研究点 (12)
Loading locations...
相似试验
已完成
1 期
A Study of Avonex to Determine the Effects of Dose Titration on the Incidence of Flu Like Symptoms in Healthy VolunteersHealthy VolunteersNCT01119677Biogen120
终止
2 期
DDAVP in the Reduction of Post-operative Ecchymosis in RhinoplastyPostoperative EcchymosisNCT01982760University Hospitals Cleveland Medical Center14
已完成
2 期
Study to Evaluate the Safety and Efficacy of Davunetide for the Treatment of Progressive Supranuclear PalsyProgressive Supranuclear PalsyNCT01110720Allon Therapeutics313
Unknown
不适用
Adaprev in Digital Flexor Tendon RepairTendon InjuriesNCT01014494Renovo44
已完成
3 期
Avatrombopag for the Treatment of Chemotherapy-Induced Thrombocytopenia in Adults With Active Non-Hematological CancersChemotherapy-induced ThrombocytopeniaNCT03471078Sobi, Inc.122