A SINGLE COUNTRY, MULTICENTER, OPEN-LABEL AND NON-RANDOMIZED CLINICAL TRIAL WITH MOROCTOCOG ALFA (AF-CC) PROPHYLAXIS AND TREATMENT OF BLEEDING EPISODES IN PREVIOUSLY TREATED PATIENTS WITH MODERATE AND SEVERE HEMOPHILIA A FOR A DURATION OF 8 WEEKS
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 50
- 试验地点
- 10
- 主要终点
- Percentage of Participants Who Developed Factor VIII (FVIII) Inhibitors
研究概览
简要总结
Moroctocog-alfa (AF-CC) is indicated for the control and prevention of hemorrhagic episodes and for routine and surgical prophylaxis in patients with hemophilia A (congenital factor VIII deficiency or classic hemophilia). The current single country, multi-centric, open label, non-randomized pragmatic clinical trial is a post-approval study to fulfill the Central Drugs Standard Control Organization (CDSCO) request for supplementary information relating to the use of moroctocog-alfa (AF-CC) in Indian subjects with hemophilia A.
The primary objective of study is to study the safety of moroctocog alfa (AF-CC) when administered for prophylaxis with respect to incidence of FVIII inhibitor development. The secondary objectives are to evaluate the incidence of adverse events (AEs) and serious adverse events (SAEs) in subjects receiving moroctocog alfa (AF-CC) prophylaxis, to evaluate the efficacy of moroctocog alfa (AF-CC) during a prophylaxis regimen, to evaluate the total annualized consumption of moroctocog alfa (AF-CC) by subjects following a prophylaxis regimen, to evaluate the efficacy of moroctocog alfa (AF-CC) for the treatment of breakthrough bleeding episodes (on-demand treatment) while following a prophylaxis regimen.
Fifty male subjects aged >/= 12 years to ≤65 years with moderate or severe hemophilia A will be enrolled in the study. The subjects will be selected based on protocol specified eligibility criteria. The overall treatment duration for each subject will be up to 8 weeks, with up to a 4-week screening period and a subsequent post-treatment 28-day safety observation period. Subjects are requested to continue in the study until 24 exposure days (EDs) or a period of up to 8 weeks on moroctocog alfa (AF-CC) treatment had occurred (whichever occurs first). Efficacy and safety assessments will be performed as specified in the protocol.
详细描述
Moroctocog-alfa (AF-CC) is indicated in India for the control and prevention of hemorrhagic episodes and for routine and surgical prophylaxis in patients with hemophilia A (congenital factor VIII deficiency or classic hemophilia). The current protocol outlines a post-approval study to fulfill the Central Drugs Standard Control Organization (CDSCO) written request for supplementary information relating to the use of moroctocog-alfa (AF-CC) in Indian subjects with hemophilia A. The additional information will include safety and efficacy of moroctocog-alfa (AF-CC) in Indian subjects with a diagnosis of congenital moderate or severe hemophilia A (FVIII:C ≤5%). The primary objective is to study the safety of moroctocog alfa (AF-CC) when administered for prophylaxis with respect to incidence of FVIII inhibitor development. The secondary objectives are to evaluate the incidence of adverse events (AEs) and serious adverse events (SAEs) in subjects receiving moroctocog alfa (AF-CC) prophylaxis, to evaluate the efficacy of moroctocog alfa (AF-CC) during a prophylaxis regimen, to evaluate the total annualized consumption of moroctocog alfa (AF-CC) by subjects following a prophylaxis regimen and to evaluate the efficacy of moroctocog alfa (AF-CC) for the treatment of breakthrough bleeding episodes (on-demand treatment) while following a prophylaxis regimen. The primary endpoint will be the proportion of subjects who develop FVIII inhibitor (≥0.6 BU/mL), as confirmed by central laboratory testing, during the course of the study. The secondary endpoints include assessment of incidence of AEs, incidence of SAEs, Annualized bleeding rate (ABR) during prophylaxis, Annualized total factor consumption (TFC) in international units (IU) and annualized TFC by weight (IU/kg) of moroctocog alfa (AF-CC) measured during the up to 8 weeks of treatment, by reason for infusion and total units consumed (across all reasons) and number of moroctocog alfa (AF-CC) infusions used to treat each bleed.
This study is a single-country, multicenter, open-label, interventional study which will be conducted in India. At least 50 male subjects aged ≥12 years to ≤65 years with moderate or severe hemophilia A (FVIII:C ≤5%) who have had at least 50 exposure days (EDs) to FVIII-containing products will be enrolled in the study. The overall treatment duration for each subject will be up to 8 weeks, with up to a 4-week screening period and a subsequent post-treatment 28-day safety observation period. Subjects are requested to continue in the study until 24 exposure days (EDs) or a period of up to 8 weeks on moroctocog alfa (AF-CC) treatment had occurred (whichever occurs first). Subjects will be treated with a dose and regimen of prophylaxis in accordance with the Local Product Development.
The following subjects will be included in this study:
- Male subjects ≥12 years to ≤65 years with a diagnosis of congenital moderate or severe hemophilia A (FVIII:C ≤5%).
- Documented history of at least 50 exposure days (EDs) to FVIII-containing products.
- Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative, parent(s)/legal guardian) has been informed of all pertinent aspects of the study. For minors under the age of legal consent in India, assent of the participating child needs to be documented for the age range 12 to 18 in addition to the parental informed consent.
Subjects presenting with any of the following will not be included in the study:
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
- •Male subjects ≥12 years to ≤65 years with a diagnosis of congenital moderate or severe hemophilia A (FVIII:C ≤5%).
- •Documented history of at least 50 exposure days (EDs) to FVIII-containing products.
- •Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative, parent(s)/legal guardian) has been informed of all pertinent aspects of the study. For minors under the age of legal consent in India, assent of the participating child needs to be documented for the age range 12 to 18 in addition to the parental informed consent.
排除标准
- •Prior history of inhibitor to FVIII or positive inhibitor testing (≥0.6 BU/mL) during Screening. Clinical signs or symptoms of decreased response to FVIII.
- •Known hypersensitivity to the active substance or any of the excipients.
- •Known allergic reaction to hamster proteins.
- •Presence of any bleeding disorder in addition to hemophilia A.
- •Participation in other studies involving investigational drug(s) (Phases 1-4) within 30 days before the current study begins and/or during study participation.
- •Planned surgery within 6 months from the start of the study.
- •Unsuitable to participate in study for any other reason as assessed by the investigator; including any disorder, except for conditions associated with hemophilia A, which in the investigator's opinion might jeopardize subject's safety or compliance with the protocol.
- •Subjects (or a legally acceptable representative) is not able to understand study documents and study procedure.
- •Immunocompromised subjects due to human immunodeficiency virus (HIV) infection (defined as viral load above or equal to 100,000 copies/mL; and for HIV+ subjects: cluster of differentiation 4 positive (CD4+) lymphocyte count below or equal to 200/μL). HIV status and CD4+ lymphocyte count results may be obtained at screening or from available medical records; results must be not older than 6 months prior to screening.
- •Subjects who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, subjects who have been previously enrolled into the study, or subjects who are Pfizer employees directly involved in the conduct of the study.
- •Planned use of any non-study medication for treatment of hemophilia (eg, other factor replacement agents, bypassing agents, or non-factor treatments [such as anti-tissue factor pathway inhibitors]).
结局指标
主要结局
Percentage of Participants Who Developed Factor VIII (FVIII) Inhibitors
时间窗: 24 exposure days or 8 weeks of treatment during the study (whichever occurred first)
FVIII inhibitor development was defined as an inhibitor titer of \>=0.6 Bethesda units per milliliter (BU)/mL as confirmed by the central laboratory during the course of the study.
次要结局
- Mean Number of Moroctocog Alfa (AF-CC) Infusions Used to Treat Each New Bleed(24 exposure days or 8 weeks of treatment during the study (whichever occurred first))
- Mean Annualized Bleeding Rate (ABR) During Prophylaxis(24 exposure days or 8 weeks of treatment during the study (whichever occurred first))
- Mean Annualized Total Factor Consumption (TFC)(24 exposure days or 8 weeks of treatment during the study (whichever occurred first))
- Number of Participants With Treatment Emergent Adverse Events (TEAEs)(Day 1 up to 28 days after last dose of study drug (approximately maximum up to 12 Weeks))
- Number of Participants With Treatment Emergent Serious Adverse Events (SAEs)(Day 1 up to 28 days after last dose of study drug (approximately maximum up to 12 Weeks))
- Mean Annualized Total Factor Consumption (TFC) by Weight(24 exposure days or 8 weeks of treatment during the study (whichever occurred first))