Odevixibat Outcomes in Patients With PFIC Versus an External Control Cohort (OvEC-PFIC)

N/AActive Not RecruitingNCT07497724

Ipsen200 enrolled

Overview

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.

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.

Study Type

OBSERVATIONAL

Enrollment

200

Conditions

PFIC - Progressive Familial Intrahepatic Cholestasis

Eligibility

Medical Language ↔ Plain English

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. OR * 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 OR * 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 A4250-008. * 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 A4250-008. 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 A4250-008. * 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.

Outcomes

Primary Outcomes

Part A: Liver transplant-free survival (LTFS)

Defined as time from Day 1 to the first occurrence of any of the following clinical events: Death (any cause); Liver Transplant (LT)

Time frame: 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 B: Liver transplant-free survival (LTFS)

As defined for Part A

Time frame: 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)

Secondary Outcomes

Part A: Event-free survival (EFS)

Defined as the time from Day 1 to the first occurrence of the following: LT; Death; Surgical Biliary Diversion (SBD, a type of surgery that reroutes the flow of bile so that less of it returns to the liver)

Part A: Surgical biliary diversion-free survival (DFS)

Defined as the time from Day 1 to the first occurrence of the following: SBD; Death (any cause)

Part A: Overall survival (OS)

Defined as time from Day 1 to death (any cause)

Time frame: 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)

As defined for Part A

Time frame: 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)

Defined as the time from Day 1 to the first occurrence of a platelet count below 150,000/mm³ at any time prior to LT

Part B: Time to progression to End-stage Liver Disease (ESLD)

As defined for Part A

Time frame: 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

Part B: Proportion of patients who died

Time frame: 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)

Part B: Proportion of patients who experience Liver Transplant (LT)

Time frame: 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)

Odevixibat Outcomes in Patients With PFIC Versus an External Control Cohort (OvEC-PFIC)

Overview

Conditions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes