IBAT Inhibitor A4250 for Cholestatic Pruritus

February 21, 2017 updated by: Hanns-Ulrich Marschall, Sahlgrenska University Hospital, Sweden

An Exploratory, Phase IIa Study to Demonstrate the Safety and Efficacy of A4250 in Patients With Primary Biliary Cirrhosis and Cholestatic Pruritus

This study will evaluate the safety, tolerability and influence on itching, bile acids and liver enzyme changes in patients with PBC (Primary Biliary Cirrhosis) treated with A4250

Study Overview

Status

Terminated

Intervention / Treatment

Detailed Description

A4250PBCpruritus (EudraCT 2014-004070-42) is an open-label exploratory study.

The primary objective of this study is to assess the safety and tolerability of A4250, 1.5 - 3 mg orally during a four-week treatment period, in patients with PBC and cholestatic pruritus, as determined by the occurrence of treatment-emergent serious adverse events (SAEs).

Other safety objectives of this study include assessment of the safety and tolerability of A4250 during a four-week treatment period, as determined by the occurrence of treatment-emergent adverse events (AEs) and changes in other safety parameters including liver and kidney function tests and vital signs.

Exploratory efficacy objectives of this study are to demonstrate the efficacy of A4250 orally on pruritus variables and on QoL and lysophosphatidic acid formation as well as evaluation of changes in pharmacodynamic parameters of bile acid metabolism such as serum and fecal bile acids, C4 and fibroblast growth factor 19 (FGF19) assessments and assessment of surrogate markers of cholestatic liver disease such as alkaline phosphatase, transaminases and bilirubin.

Study Type

Interventional

Enrollment (Actual)

9

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Göteborg, Sweden
        • Sahlgrenska Academy

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Major Inclusion Criteria:

  • Diagnosis of PBC or PBC-Autoimmune hepatitis overlap as established according to American Association for the Study of Liver Diseases/European Association for the Study of Liver (AASLD/EASL) definitions. Definite or probable PBC diagnosis, as demonstrated by the presence of ≥ 2 of the following 3 diagnostic factors:
  • History of elevated alkaline phosphatase (ALP) levels (>1.67 ULN) for at least 6 months prior to Day 1
  • Positive antimitochondrial antibodies (AMA) titer or if AMA negative or in low titer (<1:80) PBC specific antibodies (anti-GP210 and/or anti-SP100 and/or antibodies against the major M2 components (PDC-E2, 2-oxo-glutaric acid dehydrogenase complex)
  • Liver biopsy consistent with PBC;
  • Ursodeoxycholic acid (UDCA) non-responders defined as >6 months of UDCA and at the time of enrolment a serum ALP >1.67 ULN;
  • Laboratory markers of cholestasis identified within 3 months of Visit 1;
  • Treatment with cholestyramine at a dose >4g BID or colestipol > 5mg for at least 3 months;
  • The patient has a VAS-Itch of at least 30 mm during the day before baseline (Visit 2);
  • The patient is a male or non-pregnant female ≥18 years of age and ≤80 years of age with body mass index (BMI) ≥18.5 but <35 kg/m2;

Major 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;
  • Jaundice of extrahepatic origin;
  • The patient has a structural abnormality of the GI tract;
  • The patient has a known, active, clinically significant acute or chronic infection, or any major episode of infection requiring hospitalization or treatment with parenteral anti infectives within 4 weeks of treatment start (study day 1) or completion of oral anti-infective treatment within 2 weeks prior to start of screening period;
  • The patient has unexplained and clinically significant GI alarm signals (e.g., lower GI bleeding or heme-positive stool, iron-deficiency anaemia, unexplained weight loss) or systemic signs of infection or colitis;

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: A4250
A4250 once daily
A4250 once daily
Other Names:
  • IBAT Inhibitor A4250

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
•Safety and Tolerability assessed by the occurrence of treatment-emergent SAEs during the four weeks of treatment with A4250
Time Frame: 4 weeks
4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety laboratory measurements
Time Frame: 4 weeks
Changes in safety laboratory test results (including hematology, clinical chemistry and urinalysis) from baseline to Day 28 of A4250 treatment
4 weeks
VAS-Itch
Time Frame: 4 weeks
Change in VAS-Itch (most severe itch during last 24 hrs) during the fourth treatment week of A4250
4 weeks
Itching scale
Time Frame: Four weeks
Change in PBC40
Four weeks
Bile acid evaluation
Time Frame: Four weeks
Change in serum and fecal bile acids (BAs)
Four weeks
Liver biochemistry
Time Frame: Four weeks
Change in ALP
Four weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

Investigators

  • Principal Investigator: Hanns-Ulrich Marschall, MD, Sahlgrenska Academy, Institute of Medicine,

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2015

Primary Completion (Actual)

October 1, 2016

Study Completion (Actual)

October 1, 2016

Study Registration Dates

First Submitted

January 14, 2015

First Submitted That Met QC Criteria

February 10, 2015

First Posted (Estimate)

February 11, 2015

Study Record Updates

Last Update Posted (Actual)

February 23, 2017

Last Update Submitted That Met QC Criteria

February 21, 2017

Last Verified

February 1, 2017

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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