ATLAS-INH: A Phase 3 Study to Evaluate the Efficacy and Safety of Fitusiran in Patients With Hemophilia A or B, With Inhibitory Antibodies to Factor VIII or IX
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 60
- 试验地点
- 58
- 主要终点
- Estimated Annualized Bleeding Rate (ABR) for Treated Bleeds During the Efficacy Period
研究概览
简要总结
The purpose of this study was to determine the frequency of bleeding episodes in participants receiving fitusiran as prophylactic treatment of hemophilia compared to participants who were assigned to continue with their regular medication. In addition, the study assessed safety, quality of life, pharmacodynamics (PD), and pharmacokinetics (PK).
详细描述
The duration of treatment with fitusiran was 9 months. The estimated total time on study, inclusive of screening, for each participant was up to 11 months for all participants who enroll in the extension study and participants in the on-demand arm who did not enroll in the extension study. The estimated total time on study was up to 17 months in fitusiran treatment arm participants who did not enroll in the extension study due to the requirement for up to an additional 6 months of follow-up monitoring for antithrombin levels.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- Male
- 接受健康志愿者
- 否
入选标准
- •Males, greater than or equal to (>=) 12 years of age.
- •Severe hemophilia A or B with inhibitors.
- •(Severity confirmed by a central laboratory where coagulation factor VIII (FVIII) level was less than (<)1% or factor IX (FIX) level was less than or equal to [<=]2% at Screening; Inhibitors defined as inhibitor titer of >=0.6 Bethesda units per milliliter [BU/mL] or as evidenced by medical records).
- •A minimum of 6 bleeding episodes requiring BPA treatment within the last 6 months prior to screening.
- •Willing and able to comply with the study requirements and to provide written informed consent and assent.
排除标准
- •Known co-existing bleeding disorders other than hemophilia A or B.
- •Antithrombin (AT) activity <60% at Screening.
- •Co-existing thrombophilic disorder.
- •Clinically significant liver disease.
- •Active hepatitis C virus infection.
- •HIV positive with a cluster of differentiation-4 count of <200 cells/microliter.
- •History of arterial or venous thromboembolism.
- •Inadequate renal function.
- •History of multiple drug allergies or history of allergic reaction to an oligonucleotide or N-Acetylgalactosamine.
- •History of intolerance to SC injection(s).
- •Any other conditions or comorbidities that would make the participant unsuitable for enrollment or could interfere with participation in or completion of the study, per Investigator judgement.
研究组 & 干预措施
Bypassing Agents (BPA) On-demand
Participants received On-demand BPAs (use of these agents, as needed, for episodic bleeding episodes, and not on a regular regimen intended to prevent spontaneous bleeding) per Investigator discretion from Day 1 for treatment of breakthrough bleeding episodes, up to a total of 9 months.
干预措施: Bypassing agents (Drug)
Fitusiran 80 mg Prophylaxis
Participants received Fitusiran 80 mg subcutaneously (SC) as prophylaxis once monthly from Day 1, along with the on-demand BPAs (per investigator's discretion and within bleeding dosing guidelines) for treatment of breakthrough bleeding episodes, up to a total of 9 months.
干预措施: fitusiran (Drug)
结局指标
主要结局
Estimated Annualized Bleeding Rate (ABR) for Treated Bleeds During the Efficacy Period
时间窗: From Day 29 up to Day 246 or up to the last day of bleeding follow up (any day up to Day 246), whichever was the earliest
ABR for a participant during efficacy period (EP) was defined as annualized number of bleeding episodes during EP annualized to a 1-year interval of time. Treated Bleeding episode: any occurrence of hemorrhage that required administration of BPA or factor. It started from first sign of a bleed and ended no more than 72 hours after last treatment for bleed, within which any symptoms of bleeding at same location or injections less than or equal to 72 hours apart were considered the same bleeding episode. EP was defined as time duration starting from Day 29 when antithrombin (AT) lowering capacity of fitusiran had achieved therapeutic target range to the earliest of (Day 246 or last day of bleeding follow up) (maximum duration of EP: from Day 29 to Day 246). This outcome measure (OM) represents estimated results (i.e., results received by applying negative binomial \[NB\] regression model on data collected during EP).
Observed Annualized Bleeding Rate (ABR) for Treated Bleeds During the Efficacy Period
时间窗: From Day 29 up to Day 246 or up to the last day of bleeding follow up (any day up to Day 246), whichever was the earliest
ABR for a participant during EP was defined as annualized number of bleeding episodes during EP annualized to a 1-year interval of time. ABR= number of bleeding episodes during EP divided by total number of days during EP\*365.25. A bleeding episode was defined as any occurrence of hemorrhage that required administration of BPA or factor. It started from the first sign of a bleed and ended no more than 72 hours after the last treatment for the bleed, within which any symptoms of bleeding at the same location or injections less than or equal to 72 hours apart were considered the same bleeding episode. EP was defined as time duration starting from Day 29 when the AT lowering capacity of fitusiran had achieved therapeutic target range to the earliest of (Day 246 or the last day of bleeding follow up) (maximum duration of EP: from Day 29 to Day 246). This OM represents observed results (i.e., descriptive statistics values based on the data which was collected during EP).
次要结局
- Estimated Annualized Joint Bleeding Rate for Treated Bleeds During the Efficacy Period(From Day 29 up to Day 246 or up to the last day of bleeding follow up (any day up to Day 246), whichever was the earliest)
- Observed Annualized Spontaneous Bleeding Rate for Treated Bleeds During the Efficacy Period(From Day 29 up to Day 246 or up to the last day of bleeding follow up (any day up to Day 246), whichever was the earliest)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)(From Baseline (Day 1) up to 15 months (i.e. 9 months treatment period + 6-months follow-up))
- Observed Annualized Bleeding Rate (ABR) for Treated Bleeds During the Treatment Period(From Day 1 up to Day 246 or up to the last day of bleeding follow up (any day up to Day 246), whichever was the earliest)
- Health-related Quality of Life (HRQOL): Change From Baseline in Haemophilia Quality of Life Questionnaire for Adults (Haem-A-QOL) Physical Health Domain Score at Month 9(Baseline (Day 1), Month 9)
- Estimated Annualized Bleeding Rate (ABR) for Treated Bleeds During the Treatment Period(From Day 1 up to Day 246 or up to the last day of bleeding follow up (any day up to Day 246), whichever was the earliest)
- Estimated Annualized Spontaneous Bleeding Rate for Treated Bleeds During Efficacy Period(From Day 29 up to Day 246 or up to the last day of bleeding follow up (any day up to Day 246), whichever was the earliest)
- Observed Annualized Joint Bleeding Rate for Treated Bleeds During the Efficacy Period(From Day 29 up to Day 246 or up to the last day of bleeding follow up (any day up to Day 246), whichever was the earliest)
- Health-related Quality of Life (HRQOL): Change From Baseline in Haem-A-QOL Total Score at Month 9(Baseline (Day 1), Month 9)
- Estimated Annualized Bleeding Rate (ABR) for Treated Bleeds During the Onset Period(From Day 1 up to Day 28 or up to the last day of bleeding follow up (any day up to Day 28), whichever was the earliest)