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IBAT Inhibitor A4250 for Cholestatic Pruritus

Primary Purpose

Biliary Cirrhosis, Primary

Status

Terminated

Phase

Phase 2

Locations

Sweden

Study Type

Interventional

Intervention

A4250

About this trial

This is an interventional treatment trial for Biliary Cirrhosis, Primary

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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;

Sites / Locations

Sahlgrenska Academy

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

A4250

Arm Description

A4250 once daily

Outcomes

Primary Outcome Measures

•Safety and Tolerability assessed by the occurrence of treatment-emergent SAEs during the four weeks of treatment with A4250

Secondary Outcome Measures

Safety laboratory measurements

Changes in safety laboratory test results (including hematology, clinical chemistry and urinalysis) from baseline to Day 28 of A4250 treatment

VAS-Itch

Change in VAS-Itch (most severe itch during last 24 hrs) during the fourth treatment week of A4250

Itching scale

Change in PBC40

Bile acid evaluation

Change in serum and fecal bile acids (BAs)

Liver biochemistry

Change in ALP

Full Information

NCT ID

NCT02360852

First Posted

January 14, 2015

Last Updated

February 21, 2017

Sponsor

Sahlgrenska University Hospital, Sweden

Collaborators

Albireo

1. Study Identification

Unique Protocol Identification Number

NCT02360852

Brief Title

IBAT Inhibitor A4250 for Cholestatic Pruritus

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 Type

Interventional

2. Study Status

Record Verification Date

February 2017

Overall Recruitment Status

Terminated

Why Stopped

(Expected) side effects

Study Start Date

January 2015 (undefined)

Primary Completion Date

October 2016 (Actual)

Study Completion Date

October 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Sahlgrenska University Hospital, Sweden

Collaborators

Albireo

4. Oversight

Data Monitoring Committee

5. Study Description

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Biliary Cirrhosis, Primary

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

9 (Actual)

8. Arms, Groups, and Interventions

Arm Title

A4250

Arm Type

Experimental

Arm Description

A4250 once daily

Intervention Type

Drug

Intervention Name(s)

A4250

Other Intervention Name(s)

IBAT Inhibitor A4250

Intervention Description

A4250 once daily

Primary Outcome Measure Information:

Title

•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 Measure Information:

Title

Safety laboratory measurements

Description

Changes in safety laboratory test results (including hematology, clinical chemistry and urinalysis) from baseline to Day 28 of A4250 treatment

Time Frame

4 weeks

Title

VAS-Itch

Description

Change in VAS-Itch (most severe itch during last 24 hrs) during the fourth treatment week of A4250

Time Frame

4 weeks

Title

Itching scale

Description

Change in PBC40

Time Frame

Four weeks

Title

Bile acid evaluation

Description

Change in serum and fecal bile acids (BAs)

Time Frame

Four weeks

Title

Liver biochemistry

Description

Change in ALP

Time Frame

Four weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

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;

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Hanns-Ulrich Marschall, MD

Organizational Affiliation

Sahlgrenska Academy, Institute of Medicine,

Official's Role

Principal Investigator

Facility Information:

Facility Name

Sahlgrenska Academy

City

Göteborg

Country

Sweden

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

IBAT Inhibitor A4250 for Cholestatic Pruritus

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