PFIC - Progressive Familial Intrahepatic Cholestasis
Conditions
Brief summary
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.
Detailed description
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.
Interventions
None listed
Sponsors
Ipsen
Erasmus Medical Center
University Medical Center Groningen
Study design
Observational model
OTHER
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
3 Months to 100 Years
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part B: Liver transplant-free survival (LTFS) | 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 |
| Part A: Liver transplant-free survival (LTFS) | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | — |
| 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 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) | 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) | 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 the time from Day 1 to the first occurrence of the following: SBD; Death (any cause) |
| 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) | Defined as time from Day 1 to death (any cause) |
| 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 | As defined for Part A |
| 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) | 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) | From the date of first odevixibat treatment (Odevixibat Cohort) or from the from the date of SBD (External control cohort) until ESLD (2017-2025) | As defined for Part A |
| 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 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 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) | — |
Countries
France
Contacts
STUDY_DIRECTORIpsen Medical Director
Ipsen
Outcome results
None listed