IBAT Inhibitor A4250 for Cholestatic Pruritus

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02360852
Recruitment Status : Terminated ((Expected) side effects)
First Posted : February 11, 2015
Last Update Posted : February 23, 2017
Information provided by (Responsible Party):
Hanns-Ulrich Marschall, Sahlgrenska University Hospital, Sweden

Brief Summary:
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

Condition or disease Intervention/treatment Phase
Biliary Cirrhosis, Primary Drug: A4250 Phase 2

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  (Clinical Trial)
Actual Enrollment : 9 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Exploratory, Phase IIa Study to Demonstrate the Safety and Efficacy of A4250 in Patients With Primary Biliary Cirrhosis and Cholestatic Pruritus
Study Start Date : January 2015
Actual Primary Completion Date : October 2016
Actual Study Completion Date : October 2016

Arm Intervention/treatment
Experimental: A4250
A4250 once daily
Drug: A4250
A4250 once daily
Other Name: IBAT Inhibitor A4250

Primary Outcome Measures :
  1. •Safety and Tolerability assessed by the occurrence of treatment-emergent SAEs during the four weeks of treatment with A4250 [ Time Frame: 4 weeks ]

Secondary Outcome Measures :
  1. 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

  2. VAS-Itch [ Time Frame: 4 weeks ]
    Change in VAS-Itch (most severe itch during last 24 hrs) during the fourth treatment week of A4250

  3. Itching scale [ Time Frame: Four weeks ]
    Change in PBC40

  4. Bile acid evaluation [ Time Frame: Four weeks ]
    Change in serum and fecal bile acids (BAs)

  5. Liver biochemistry [ Time Frame: Four weeks ]
    Change in ALP

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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;

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02360852

Sahlgrenska Academy
Göteborg, Sweden
Sponsors and Collaborators
Sahlgrenska University Hospital, Sweden
Principal Investigator: Hanns-Ulrich Marschall, MD Sahlgrenska Academy, Institute of Medicine,

Responsible Party: Hanns-Ulrich Marschall, MD, Sahlgrenska University Hospital, Sweden Identifier: NCT02360852     History of Changes
Other Study ID Numbers: A4250 PBC Pruritus
First Posted: February 11, 2015    Key Record Dates
Last Update Posted: February 23, 2017
Last Verified: February 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Liver Cirrhosis
Liver Cirrhosis, Biliary
Pathologic Processes
Liver Diseases
Digestive System Diseases
Skin Diseases
Skin Manifestations
Signs and Symptoms
Cholestasis, Intrahepatic
Bile Duct Diseases
Biliary Tract Diseases