NCT06297486撤回3 期
A Phase 3, Single-arm, Open-label, Multicenter Study of the Safety and Efficacy of Dirloctocogene Samoparvovec (SPK 8011, Adeno-associated Viral Vector With B-domain Deleted Human Factor VIII Gene) in Adults With Severe or Moderately Severe Hemophilia A
适应症
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 入组人数
- 85
- 试验地点
- 54
- 主要终点
- Annualized Bleed Rate (ABR) for All Bleeds [Cohort A]
研究概览
简要总结
The purpose of this study is to evaluate the efficacy of SPK-8011 in preventing bleed episodes compared with FVIII prophylaxis in participants with hemophilia A without FVIII inhibitors on routine FVIII prophylaxis.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Have a negative anti-AAV-Spark200 neutralizing antibody (NAb) test result.
- •Are adult males with severe or moderately severe hemophilia A, defined as endogenous FVIII activity ≤3%, as documented by a certified laboratory (historically or during the Screening Period) and where the FVIII:C level is measured more than 96 hours after the prior dose of an extended-half-life FVIII
- •Have ≥150 documented exposure days to an FVIII protein product such as recombinant, plasma-derived, or extended half-life FVIII product
- •Have no prior history of hypersensitivity or anaphylaxis associated with the administration of any FVIII product.
- •Have screening hepatic ultrasound without evidence of cirrhosis and no laboratory or clinical evidence per the Investigator's judgment of advanced liver disease or cirrhosis.
- •Have a negative test for inhibitor against FVIII (ie, <0.6 Bethesda units [BU]) during screening.
- •Have no documented FVIII inhibitor (ie, <0.6 BU), FVIII half-life <6 hours, or FVIII recovery <66% in the 5 years prior to screening.
- •Candidates who completed successful immune tolerance induction (ITI) at least 5 years before screening are eligible, provided they have had no evidence of inhibitor recurrence (permanent or temporary) within 5 years prior to screening as may be indicated by detection of an inhibitor, FVIII half-life <6 hours, or FVIII recovery <66% since completing ITI.
- •If human immunodeficiency virus (HIV)-positive at screening, have an adequate cluster of differentiation 4 (CD4) count (>200/mm3) and undetectable viral load (<50 genome copies [gc]/mL), are on an antiretroviral drug regimen, and have completed at least 12 weeks of this treatment regimen prior to screening.
- •Meet the following inclusion criteria by cohort:
- •Cohort A: have documented history of prior treatment with FVIII prophylaxis (defined as receiving a prescribed dose and frequency of FVIII infusions with the intent to treat continuously for 52 weeks per year) for a minimum of 6 months prior to screening; and are willing to continue their FVIII prophylaxis during the Lead-In Period of this study (minimum of 24 weeks).
- •Cohort B: have documented history of prior treatment with FVIII on demand for a minimum of 6 months that shows ≥5 treated bleeds in the last 6 months prior to screening.
- •Cohort C: have documented history of prior treatment with emicizumab prophylaxis for a minimum of 6 months prior to screening.
排除标准
- •Have an inherited or acquired bleeding disorder other than hemophilia A
- •Have inherited or acquired thrombophilia, have signs of thromboembolic disease in the Investigator's judgment, or are on current treatment for thromboembolic disease. A history of previous catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing is not considered an exclusion criterion.
- •Have concurrent disease, treatment, or abnormality in clinical laboratory tests that could interfere with the conduct of the study or that would, in the opinion of the Investigator or Sponsor, preclude the candidate's safe participation in and completion of the study, or the interpretation of the study results.
结局指标
主要结局
Annualized Bleed Rate (ABR) for All Bleeds [Cohort A]
时间窗: Up to 66 weeks post-SPK-8011 infusion
次要结局
- ABR for treated bleeds [Cohort A](Up to approximately 10 years)
- Mean ABR for all bleeds and treated bleeds [Cohort C](Up to approximately 10 years)
- FVIII: C levels over time from Week 26 [Cohort C](Up to approximately 10 years)
- Median Time to First Immunomodulation-related Corticosteroid Dose [Cohorts A, B, C](Up to approximately 10 years)
- Annualized FVIII dosage [Cohort A](Up to approximately 10 years)
- Mean Change of Total Hemophilia Joint Health Score [Cohort A](Baseline, up to 66 weeks post-SPK-8011 infusion)
- Proportion of Participants Who Receive IV Methylprednisolone (IVMP) Prior to Week 8 (Early IVMP) [Cohorts A, B, C](Up to approximately 10 years)
- Median FVIII: C levels [Cohort A](Up to approximately 10 years)
- FVIII:C levels over time [Cohort A](Up to approximately 10 years)
- Proportion of Participants Who Receive Secondary Oral Immunomodulation [Cohorts A, B, C](Up to approximately 10 years)
- Proportion of participants with treatment-related AEs of Infusion Reaction [Cohorts A, B, C](Up to approximately 10 years)
- Percentage of Participants with ABR=0 for all bleeds; treated bleeds; treated spontaneous bleeds; and treated joint and target joint bleeds [Cohort A](Up to approximately 10 years)
- ABR for treated spontaneous, joint, and target joint bleeds [Cohort A](Up to approximately 10 years)
- Proportion of Resolved Target Joints [Cohort A](Up to approximately 10 years)
- Median Duration of Secondary Oral Immunomodulation [Cohorts A, B, C](Up to approximately 10 years)
- Proportion of participants with AESIs [Cohorts A, B, C](Up to approximately 10 years)
- Proportion of Participants with FVIII Inhibitor Development [Cohorts A, B, C](Up to approximately 10 years)
- Proportion of participants with Treatment-related AEs of ALT Elevation [Cohorts A, B, C](Up to approximately 10 years)
- Proportion of participants with AEs and SAEs [Cohorts A, B, C](Up to approximately 10 years)
- Number of participants with abnormal physical exam findings, abnormal vital signs, and abnormal selected clinical laboratory test results [Cohorts A, B, C](Up to approximately 10 years)
研究者
研究点 (54)
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