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| Name | Class |
|---|---|
| Erasmus Medical Center | OTHER |
| University Medical Center Groningen | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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) |
| 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) |
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Part A Eligibility: Comparisons to Evaluate the Effect of Odevixibat Versus SBD-naïve
Odevixibat Cohort:
OR
OR
External Control Cohort:
Part B Eligibility: Comparisons to Evaluate the Effect of Odevixibat Versus SBD Odevixibat Cohort
External Control Cohort:
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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).
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| Name | Affiliation | Role |
|---|---|---|
| Ipsen Medical Director | Ipsen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Not applicable - retrospective secondary use of data | Paris | France |
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.
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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.
Further details on Ipsen's sharing criteria and process for sharing are available here (https://www.ipsen.com/science/clinical-trials/clinical-data-transparency/).
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| ID | Term |
|---|---|
| C535933 | Cholestasis, progressive familial intrahepatic 1 |
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| 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) |