Analysis of the Effect of Odevixibat (A4250) Versus External Controls on Clinical Outcomes in Patients With PFIC (Odevixibat Versus External Control [OvEC]-PFIC)
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- Ipsen
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Part A: Liver transplant-free survival (LTFS)
研究概览
简要总结
Progressive familial intrahepatic cholestasis (PFIC) is a rare inherited liver disease that causes a build-up of bile acids in the liver. This can lead to severe itching (pruritus), poor sleep, impaired growth, liver damage, and in some cases the need for surgery or liver transplantation.
The purpose of this non-interventional, retrospective study is to compare long-term health outcomes in patients with PFIC. The comparison is between patients who received odevixibat in two odevixibat clinical trials (Studies A4250-005 and A4250-008) and an aligned, balanced external control cohort of patients with PFIC from the Natural course and Prognosis of PFIC and Effect of biliary Diversion (NAPPED) registry who were not treated with odevixibat (or other ileal bile acid transporter [IBAT] inhibitors). Outcomes such as liver transplantation, death, and surgical biliary diversion (SBD) will be examined to better understand how treatment with odevixibat compares to the natural course of PFIC. This study aims to provide a robust comparative evaluation of long-term clinical outcomes with odevixibat.
详细描述
This study analysis consists of two parts: Part A will evaluate the effect of odevixibat on clinical outcomes in patients without prior SBD (i.e., SBD-naïve) who were treated with odevixibat versus SBD-naïve external controls who were not treated with odevixibat; Part B will evaluate the effect of odevixibat on clinical outcomes by comparing outcomes in patients without prior SBD who were treated with odevixibat versus external controls who underwent SBD and were not treated with odevixibat.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 3 Months 至 100 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Part A Eligibility: Comparisons to Evaluate the Effect of Odevixibat Versus SBD-naïve
- •Odevixibat Cohort:
- •Patients treated with odevixibat in A4250-005 with at least one post-odevixibat assessment and who did not have prior LT or SBD.
- •Patients treated with placebo in A4250-005, first received odevixibat in Cohort 1 of A4250-008 with at least one post-odevixibat assessment, and meet the additional eligibility criteria
- •Patients treated with odevixibat in Cohort 2 of A4250-008 with at least one post-odevixibat assessment and who meet the additional eligibility criteria
- •External Control Cohort:
- •A male or female patient in NAPPED registry not enrolled in A4250-005 or A4250-
- •The patient must be IBAT inhibitor-naïve (has not received prior treatment with odevixibat, maralixibat, or other IBAT inhibitors).
- •Patients must have clinical genetic confirmation of PFIC (any type), excluding known pathologic variations of the ABCB11 gene that predict complete absence of the BSEP protein.
- •The patient has at least one visit in NAPPED (the first of which becomes the Day 1 visit for this cohort) where they meet the eligibility criteria
- •Patients must be in the regions that participated in A4250-
- •Part B Eligibility: Comparisons to Evaluate the Effect of Odevixibat Versus SBD Odevixibat Cohort
- •Same as Part A
- •External Control Cohort:
- •A male or female patient in NAPPED registry with clinical diagnosis of PFIC (any type) and not enrolled in A4250-005 or A4250-
- •The patient must be IBAT inhibitor-naïve (has not received prior treatment with odevixibat, maralixibat, or other IBAT inhibitors).
- •Patient must have clinical genetic confirmation of PFIC (any type), excluding known pathologic variations of the ABCB11 gene that predict complete absence of the BSEP protein;
- •The patient underwent SBD (the date of surgery becomes the Day 1 visit for this cohort) but did not previously undergo a LT.
- •The patient meets the additional eligibility criteria.
- •Patients must be in the regions that participated in A4250-008.
排除标准
- 未提供
研究组 & 干预措施
Odevixibat Cohort
Participants who were treated with odevixibat from two odevixibat clinical trials (Studies A4250-005 and A4250-008) Eligibility criteria for Part A and Part B analyses are described in the Eligibility section.
External Control Cohort
Participants who were not treated with odevixibat or any other IBAT inhibitor from the NAtural course and Prognosis of PFIC and Effect of biliary Diversion (NAPPED) registry Eligibility criteria for Part A and Part B analyses are described in the Eligibility section.
结局指标
主要结局
Part A: Liver transplant-free survival (LTFS)
时间窗: From the date of first odevixibat treatment or from the date of first registry entry into NAPPED group where OvEC cohort eligibility criteria were met, until the first occurrence of the defined event or last available follow-up (2017-2025)
Defined as time from Day 1 to the first occurrence of any of the following clinical events: Death (any cause); Liver Transplant (LT)
Part B: Liver transplant-free survival (LTFS)
时间窗: From the date of first odevixibat treatment (Odevixibat Cohort) or from the from the date of SBD (External control cohort) until the first occurrence of the defined event or last available follow-up (2017-2025)
As defined for Part A
次要结局
- Part A: Event-free survival (EFS)(From the date of first odevixibat treatment or from the date of first registry entry into NAPPED group where OvEC cohort eligibility criteria were met, until the first occurrence of the defined event or last available follow-up (2017-2025))
- Part A: Surgical biliary diversion-free survival (DFS)(From the date of first odevixibat treatment or from the date of first registry entry into NAPPED group where OvEC cohort eligibility criteria were met, until the first occurrence of the defined event or last available follow-up (2017-2025))
- Part A: Overall survival (OS)(From the date of first odevixibat treatment (Odevixibat Cohort) or from the date of first registry entry into NAPPED group where OvEC cohort eligibility criteria were met (External control Cohort), until death (any cause) (2017-2025))
- Part B: Overall survival (OS)(From the date of first odevixibat treatment (Odevixibat Cohort) or from the from the date of SBD (External control cohort) until death (any cause) (2017-2025)
- Part A: Time to progression to End-stage Liver Disease (ESLD)(From the date of first odevixibat treatment (Odevixibat Cohort) or from the date of first registry entry into NAPPED group where OvEC cohort eligibility criteria were met (External control Cohort), until ESLD (2017-2025))
- Part B: Time to progression to End-stage Liver Disease (ESLD)(From the date of first odevixibat treatment (Odevixibat Cohort) or from the from the date of SBD (External control cohort) until ESLD (2017-2025))
- Part A: Proportion of patients who died(From the date of first odevixibat treatment (Odevixibat Cohort) or from the date of first registry entry into NAPPED group where OvEC cohort eligibility criteria were met (External control Cohort), until death (any cause) (2017-2025))
- Part B: Proportion of patients who died(From the date of first odevixibat treatment (Odevixibat Cohort) or from the from the date of SBD (External control cohort) until death (any cause) (2017-2025)])
- Part A: Proportion of patients who experience Liver Transplant (LT)(From the date of first odevixibat treatment (Odevixibat Cohort) or from the date of first registry entry into NAPPED group where OvEC cohort eligibility criteria were met (External control Cohort), until LT (2017-2025))
- Part B: Proportion of patients who experience Liver Transplant (LT)(From the date of first odevixibat treatment (Odevixibat Cohort) or from the from the date of SBD (External control cohort) until LT (2017-2025))
- Part A: Proportion of patients who experience surgical biliary diversion (SBD)(From the date of first odevixibat treatment (Odevixibat Cohort) or from the date of first registry entry into NAPPED group where OvEC cohort eligibility criteria were met (External control Cohort), until SBD (2017-2025))