A4250, an IBAT Inhibitor in Pediatric Cholestasis

An Exploratory Phase II Study to Demonstrate the Safety and Efficacy of A4250 in Children With Cholestatic Pruritus

This study will evaluate A4250 (IBATinhibitor) as a treatment option in pediatric patients with chronic cholestasis with main emphasis on safety evaluation and on effects on pruritus

Study Overview

• Status: Completed
• Conditions: Pediatric Cholestasis
• Intervention / Treatment: Drug: A4250

Detailed Description

The primary aims of this Phase II exploratory study in patients treated with A4250 due to cholestasis induced pruritus are to:

• Assess the safety and tolerability of A4250, orally administered first as a single dose and then during a four week treatment period, as determined by the occurrence of treatment-emergent SAEs
• Explore changes in serum total bile acids after a four week treatment period

Secondary safety aims include assessment of the safety and tolerability of A4250, orally administered first as a single dose and then during a four week treatment period, as determined by the occurrence of treatment-emergent AEs and changes in safety parameters including laboratory tests and vital signs

Secondary efficacy aims are to:

• Demonstrate the efficacy of A4250, orally administered during a four week treatment period, on liver biochemistry variables and on pruritus parameters
• Evaluate the pharmacokinetic properties of A4250 orally administered first as a single dose and then after a four week treatment period
• Evaluate changes in VAS-itching score after a four week treatment period

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark
    • Department of Pediatric and Adolescent Medicine Rigshospitalet
• France
  • Paris, France
    • Department of Pediatric Gastroenterology Hepatology-Nutrition, Necker-Enfants maladies hospital
  • Orsay
    • Paris, Orsay, France
      • Pediatric Hepatology and Liver Transplantation, University Hospitals of Paris-Sud
• Germany
  • Hannover, Germany
    • Pediatric Gastroenterology and Hepatology, Pediatric Surgery, Hannover
  • Tuebingen, Germany
    • Gastroenterology/Hepatology, University Hospital for Children and Adolescents
• Sweden
  • Stockholm, Sweden, 17176
    • Henrik Arnell
• United Kingdom
  • London, United Kingdom
    • King's College Hospital NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of pruritus due to chronic cholestasis based on history and investigator judgment. This will include but will not be restricted to patients with Progressive familial intrahepatic cholestasis (PFIC), Alagille syndrome (ALGS), Biliary Atresia and Sclerosing Cholangitis

Exclusion Criteria:

• Any condition that in the opinion of the investigator constitutes a risk for the patient or a contraindication for participation and completion of the study, or could interfere with study objectives, conduct, or evaluations
• Clinical or biochemical signs of decompensated liver disease
• Liver transplantation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A4250 1; Dose I	Drug: A4250; A4250
Active Comparator: A4250 2; Dose 2	Drug: A4250; A4250
Active Comparator: A4250 3; Dose 3	Drug: A4250; A4250
Active Comparator: A4250 4; Dose 4	Drug: A4250; A4250
Active Comparator: A4250 5; Dose 5	Drug: A4250; A4250
Active Comparator: A4250 6; Dose 6	Drug: A4250; A4250

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AE evaluation	Treatment-emergent SAEs Adverse events	4 wks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bile acid changes	Evaluation of bile acids	4 weeks

Collaborators and Investigators

• Sponsor: Albireo
• Investigators: Study Director: Ipsen Medical Director, Ipsen

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (Actual): March 17, 2017
• Study Completion (Actual): March 17, 2017

Study Registration Dates

• First Submitted: November 23, 2015
• First Submitted That Met QC Criteria: December 14, 2015
• First Posted (Estimated): December 15, 2015

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Biliary Tract Diseases; Bile Duct Diseases; Cholestasis
• Other Study ID Numbers: A4250-003

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. Any requests should be submitted to www.vivli.org for assessment by an independent scientific review board.

• 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 EU or after the primary manuscript describing the results has been accepted for publication, whichever is later.
• IPD Sharing Access Criteria: Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).