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

Analysis of the Effect of Odevixibat (A4250) Versus External Controls on Clinical Outcomes in Patients With PFIC (Odevixibat Versus External Control [OvEC]-PFIC)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: PFIC - Progressive Familial Intrahepatic Cholestasis

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.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

Study Locations

• France
  • Paris, France
    • Not applicable - retrospective secondary use of data

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population source comprises patients of any age (paediatric and adults) with genetically confirmed PFIC who have either participated in odevixibat interventional trials (A4250-005 and A4250-008) or are included in the retrospective natural history registry (NAPPED).

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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)	Defined as the time from Day 1 to the first occurrence of the following: SBD; Death (any cause)	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)	Defined as time from Day 1 to death (any cause)	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	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	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)	As defined for Part A	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)

Collaborators and Investigators

• Sponsor: Ipsen
• Collaborators: University Medical Center Groningen; Erasmus Medical Center
• Investigators: Study Director: Ipsen Medical Director, Ipsen

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2026
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: March 23, 2026
• First Submitted That Met QC Criteria: March 23, 2026
• First Posted (Actual): March 27, 2026

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cholestasis, progressive familial intrahepatic 1
• Other Study ID Numbers: CLIN-60240-458

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications.

Patient level data will be anonymized and study documents will be redacted to protect the privacy of study participants.

• IPD Sharing Time Frame: Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and/or EU.
• IPD Sharing Access Criteria: Further details on Ipsen's sharing criteria and process for sharing are available here (https://www.ipsen.com/science/clinical-trials/clinical-data-transparency/).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No