Biliary Cirrhosis, PrimaryPhase 2NCT02360852
IBAT Inhibitor A4250 for Cholestatic Pruritus
A Phase 2 study testing A4250 in people with Biliary Cirrhosis, Primary, run by Sahlgrenska University Hospital at 1 site in Sweden.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Biliary Cirrhosis, Primary
- What is being tested?
- A4250
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteSweden
- Study dates
- Jan 2015to Oct 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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;
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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
Read the 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.
- Conditions
- Biliary Cirrhosis, Primary
- Being tested
- A4250
- Medical subject headings
- Liver Cirrhosis, Biliary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
A4250Drug
Also called IBAT Inhibitor A4250
A4250 once daily
| Study group | Role | What they receive |
|---|---|---|
| A4250 | Experimental | A4250 once daily Receives: Drug: A4250 |
What is being measured
The primary outcome is the main question the study is designed to answer.
•Safety and Tolerability assessed by the occurrence of treatment-emergent SAEs during the four weeks of treatment with A4250
Measured: 4 weeks
Secondary outcomes (5)
Safety laboratory measurements
Changes in safety laboratory test results (including hematology, clinical chemistry and urinalysis) from baseline to Day 28 of A4250 treatment
Measured: 4 weeks
VAS-Itch
Change in VAS-Itch (most severe itch during last 24 hrs) during the fourth treatment week of A4250
Measured: 4 weeks
Itching scale
Change in PBC40
Measured: Four weeks
Bile acid evaluation
Change in serum and fecal bile acids (BAs)
Measured: Four weeks
Liver biochemistry
Change in ALP
Measured: Four weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2015 (estimated)
- Study startJan 2015
- Primary completionOct 2016
- Study completionOct 2016
Why it stopped: (Expected) side effects
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Biliary Cirrhosis, PrimaryStudies of the same condition, open and under way.
- More trials run by Sahlgrenska University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sahlgrenska University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Albireo
- Responsible party
- Principal investigator, Hanns-Ulrich Marschall, Sahlgrenska University Hospital
- Investigators
- Hanns-Ulrich Marschall, MD, Principal investigator, Sahlgrenska Academy, Institute of Medicine,
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02360852
- Sponsor's protocol ID
- A4250 PBC Pruritus
- Status last verified
- Feb 2017
- First submitted
- 14 Jan 2015
- Last updated
- 23 Feb 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory, Phase IIa Study to Demonstrate the Safety and Efficacy of A4250 in Patients With Primary Biliary Cirrhosis and Cholestatic Pruritus
- ClinicalTrials.gov ID
- NCT02360852
- Acronym / sponsor ID
- A4250 PBC Pruritus
- Conditions
- Biliary Cirrhosis, Primary
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: (Expected) side effects
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Sahlgrenska University HospitalUniversity, hospital or other
- Collaborators
- Albireo
- Study start
- Jan 2015
- Primary completion
- Oct 2016 (actual)
- Study completion
- Oct 2016 (actual)
- First posted
- 11 Feb 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| A4250 | Experimental | Drug: A4250A4250 once daily |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| A4250Also: IBAT Inhibitor A4250A4250 once daily | Drug | A4250 |
Primary outcome
•Safety and Tolerability assessed by the occurrence of treatment-emergent SAEs during the four weeks of treatment with A4250
Time frame: 4 weeks
5 secondary outcomes
Safety laboratory measurements
Time frame: 4 weeks
VAS-Itch
Time frame: 4 weeks
Itching scale
Time frame: Four weeks
Bile acid evaluation
Time frame: Four weeks
Liver biochemistry
Time frame: Four weeks
Results and safety
The study was stopped early (reason given: (Expected) side effects). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2017.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hanns-Ulrich Marschall, MD principal investigator
Sahlgrenska Academy, Institute of Medicine,
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing A4250 in people with Biliary Cirrhosis, Primary, run by Sahlgrenska University Hospital at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 23 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: (Expected) side effects). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
•Safety and Tolerability assessed by the occurrence of treatment-emergent SAEs during the four weeks of treatment with A4250 (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2017.