A Phase 1, Single-Site, Open-Label Study to Assess Pharmacokinetics of Efanesoctocog Alfa (BIVV001), Standard Half-Life and Extended Half-Life FVIII After Each Single Intravenous Injection in a Fixed Sequence, in Previously Treated Adults With Severe Hemophilia A
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- Half-life of BIVV001
研究概览
简要总结
Primary objective
• To assess the half-life of BIVV001, Standard Half-Life (SHL) rFVIII and Extended Half-Life (EHL) rFVIII after a single intravenous (IV) injection
Secondary objectives
- To characterize additional pharmacokinetic (PK) parameters of BIVV001, SHL rFVIII and EHL rFVIII after a single IV injection
- To evaluate the safety and tolerability of a single IV injection of BIVV001
详细描述
This is a Phase 1, single center, open-label, sequential treatment, 3-period fixed sequence study to assess PK profiles of BIVV001, SHL and EHL rFVIII after a single IV injection in male, previously treated patients, 18-65 years of age, with severe hemophilia A (defined as <1 IU/dL [<1%] endogenous FVIII).
The expected duration of the study is up to approximately 67 days including
- Screening and washout up to 28 days,
- Advate® dosing, PK sampling, including washout: approximately 4 days,
- Adynovi® dosing and PK sampling, including washout: approximately 7 days,
- BIVV001 dosing and PK sampling: approximately 14 days, Remainder of Safety Observation Period: approximately 14 days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Severe hemophilia A, defined as <1 IU/dL (<1%) endogenous FVIII activity.
- •Previous treatment for hemophilia A, defined as at least 150 days documented prior exposure to any recombinant and/or plasma-derived FVIII and/or cryoprecipitate products at Day
- •Platelet count ≥100,000 cells/µL at Screening.
- •A participant known to be human immunodeficiency virus (HIV) antibody positive, either previously documented or identified from screening assessments, must have the following results prior to enrollment. (CD4 lymphocyte count >200 cells/mm³ - Viral load of <400 copies/mL).
排除标准
- •Any concurrent clinically significant liver disease that, in the opinion of the Investigator, would make the participant unsuitable for enrollment. This may include, but is not limited to cirrhosis, portal hypertension, and acute hepatitis.
- •Serious active bacterial, fungal or viral infection (other than chronic hepatitis or HIV) present within 30 days of Screening.
- •Other known coagulation disorder(s) in addition to hemophilia A.
- •History of hypersensitivity or anaphylaxis associated with any FVIII product.
- •History of a positive inhibitor test defined as ≥0.6 BU/mL, or any value greater than or equal to the lower sensitivity cut-off for laboratories with cut-offs for inhibitor detection between 0.7 and 1.0 BU/mL, or clinical signs or symptoms of decreased response to FVIII administrations. Family history of inhibitors will not exclude the participant.
- •Positive inhibitor result, defined as ≥0.6 BU/mL at Screening.
- •Major surgery within 8 weeks of Screening.
- •Sensitivity to any of the study interventions, or components thereof, or drug or other allergy.
- •The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
研究组 & 干预措施
efanesoctocog alfa (BIVV001)
Each participant will be sequentially dosed with three single intravenous (IV) doses of first rFVIII (Advate®), second Polyethylene Glycol (PEG)-rFVIII (Adynovi® or Adynovate®), and lastly, BIVV001
干预措施: Efanesoctocog alfa (Drug)
efanesoctocog alfa (BIVV001)
Each participant will be sequentially dosed with three single intravenous (IV) doses of first rFVIII (Advate®), second Polyethylene Glycol (PEG)-rFVIII (Adynovi® or Adynovate®), and lastly, BIVV001
干预措施: Octocog alfa (Drug)
efanesoctocog alfa (BIVV001)
Each participant will be sequentially dosed with three single intravenous (IV) doses of first rFVIII (Advate®), second Polyethylene Glycol (PEG)-rFVIII (Adynovi® or Adynovate®), and lastly, BIVV001
干预措施: Rurioctocog alfa pegol (Drug)
结局指标
主要结局
Half-life of BIVV001
时间窗: BIVV001 period: Predose, and post-dose from 0.17 hr to 336 hr, and at day 28
Half-life of SHL rFVIII
时间窗: Advate® period: Predose, and post-dose from 0.17 hr to 72 hr
Half-Life of EHL rFVIII
时间窗: Adynovi® period: Predose, and post-dose from 0.17 hr to 120 hr
次要结局
- Assessment of PK parameter : clearance (CL)(Predose of each period, 0.17 hr to 72 hr for Advate® ; 0.17 hr to 120 hr for Adynovi® ; 0.17 hr to 336 hr and at day 28 for BIVV001)
- Assessment of PK parameter : mean residence time (MRT)(Predose of each period, 0.17 hr to 72 hr for Advate® ; 0.17 hr to 120 hr for Adynovi® ; 0.17 hr to 336 hr and at day 28 for BIVV001)
- Assessment of PK parameter : incremental recovery (IR)(Predose of each period, 0.17 hr to 72 hr for Advate® ; 0.17 hr to 120 hr for Adynovi® ; 0.17 hr to 336 hr and at day 28 for BIVV001)
- Number of participants with Adverse events (AE), serious AEs and treatment-emergent AEs (TEAEs)(From Day 1 up to 28 days after administration of BIVV001 (total 39 days including Advate® and Adynovi® period))
- Development of inhibitors (neutralizing antibodies directed against FVIII)(Advate® period: Pre-dose; Adynovi® period: Pre-dose; BIVV001 period: Pre-dose and at day 14 and 28 after administration.)
- Assessment of pharmacokinetic (PK) parameter : maximum activity (Cmax)(Predose of each period, 0.17 hr to 72 hr for Advate® ; 0.17 hr to 120 hr for Adynovi® ; 0.17 hr to 336 hr and at day 28 for BIVV001)
- Assessment of PK parameter : volume of distribution at steady state (Vss)(Predose of each period, 0.17 hr to 72 hr for Advate® ; 0.17 hr to 120 hr for Adynovi® ; 0.17 hr to 336 hr and at day 28 for BIVV001)
- Assessment of PK parameter : area under the activity time curve extrapolated to infinity (AUC∞)(Predose of each period, 0.17 hr to 72 hr for Advate® ; 0.17 hr to 120 hr for Adynovi® ; 0.17 hr to 336 hr and at day 28 for BIVV001)