PBCPhase 3BEZURSONCT01654731
Phase 3 Study of Bezafibrate in Combination With Ursodeoxycholic Acid in Primary Biliary Cirrhosis
A Phase 3 study testing Bezafibrate in people with PBC, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease that eventually leads to end-stage liver failure and death unless liver transplantation (LT) is performed. Ursodeoxycholic acid (UDCA) administered orally at the daily dose of 13-15 mg/kg is currently the only drug approved for the treatment of… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- PBC
- What is being tested?
- Bezafibrate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteFrance
- Study dates
- 15 Oct 2012to 31 Dec 2016
- Phase
- Phase 3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age > 18
- Patient with PBC defined by 2 in 3 of the following criteria Positive antimitochondrial antibody type M2. Abnormal serum alkaline phosphatases (ALP > 1,5N) and aminotransferase (AST or ALT > 1N) activities.
- Histological hepatic injuries consistent with PBC from biopsy specimens of at least 10 mm.
- Patient treated with UDCA at the dose of 13 to 15 mg/kg/d (consistent to the AMM)
- Patients showing an incomplete biochemical response to UDCA as defined by : ALP > 1,5N or AST > 1,5N or total bilirubin >17 µmol/l (with conjugated bilirubin > 8 µmol/l) after ≥ 3 months of UDCA at the dose of 13 - 15 mg/kg/day.
Who cannot join
- Unsigned consent.
- Patient with no social insurance or having medical assistant of state
- Ascites or gastrointestinal bleeding (or history of these)
- Serum total bilirubinemia > 50 μmols/L (3 mg/dl) (sample < 3 months)
- Serum albuminemia < 35 g/l (sample < 3 months)
- Prothrombin index < 70% (sample < 3 months)
Show all 16Show fewer
- Platelet count < 100000/mm3 (sample < 3 months)
- Treatment with corticosteroids, immunosuppressive agents, fibrates (or other PPAR-agonists) or statin in the last 3 months
- Any comorbidity susceptible to cause a hepatic impairment (HBV, HCV, or HIV seropositivity; excessive alcohol consumption; hemochromatosis, Wilson's disease, α1 antitrypsin deficiency; celiac disease; uncontrolled dysthyroidism; autoimmune hepatitis, inflammatory colitis)
- Any severe comorbidity decreasing life expectancy
- Intolerance or hypersensitivity to fibrates, to one of these components or other fibrates in general
- Known photosensitivity reaction to fibrates
- Pregnancy or desire of pregnancy
- Breast-feeding
- Renal failure (clearance of creatinine < 60 ml/mn)
- Patient with congenital galactosemia, syndrome of glucose malabsorption, lactase deficiency due to the presence of lactose in tablets of bezafibrate 400 mg
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Multicenter, Randomized, Double-blind Placebo Controlled Trial of Bezafibrate for the Treatment of Primary Biliary Cirrhosis in Patients With Incomplete Response to Ursodesoxycholic Acid Therapy.
Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease that eventually leads to end-stage liver failure and death unless liver transplantation (LT) is performed. Ursodeoxycholic acid (UDCA) administered orally at the daily dose of 13-15 mg/kg is currently the only drug approved for the treatment of PBC. UDCA consistently improves biochemical liver tests, prolongs survival without LT, and delays histological progression as well as the occurrence of portal hypertension. However, a significant proportion (40%) of patients treated with UDCA shows an incomplete biochemical response and remains at high risk of death or LT. The development of new treatments in combination with UDCA is therefore needed. Several candidates exist among which is Bezafibrate. Bezafibrate belongs to the fibrates' pharmacological class, which has been developed 4 decades ago for the treatment of mixed hyperlipidaemia. Bezafibrate is cheap, widely available and well tolerated. There is now a substantial body of circumstantial evidence supporting that fibrates, and Bezafibrate in particular, are well tolerated and can improve biochemical liver tests in patients with PBC with incomplete response to UDCA. However, despite several positive successful pilot studies, there are still no phase 3 randomized placebo-controlled trials of fibrates for the treatment of PBC. The purpose of this protocol is therefore to conduct such a trial in a selected population of patients with PBC based on an incomplete biochemical response after 6 months of UDCA therapy.
Read the detailed description
This is a multi-center, randomized (treatment will be assigned by chance), placebo-controlled (an inactive substance will be compared with the test drug to see whether the drug has a real effect), parallel-group (two or more groups of patients will receive different treatments) study that will assess the efficacy and safety of bezafibrate in patients with primary biliary cirrhosis (PBC) who had an inadequate biochemical response to ursodeoxycholic acid, as defined by the Paris II criteria. Bezafibrate 400 mg or placebo will be daily administered in combination with ursodeoxycholic acid (UDCA) 13-15 mg/kg/d for 24 months. Patient safety will be monitored. Primary end-point will be the percentage of patients with a complete normalization of the following biochemical tests: alkaline phosphatase, aminotransferases, total bilirubin, serum albumin, and prothrombin index. Secondary endpoints will include the percentage of drug-related adverse events, survival rates without liver transplantation or liver decompensation, time course of non-invasive liver fibrosis measurements (Fibroscan, serum hyaluronic acid), time course of liver histological parameters (fibrosis stage, necro-inflammatory grade, ductopenia) assessed on percutaneous biopsy specimens, time course of endoscopic, ultrasound, and biochemical features of portal hypertension, time course of pruritus and of quality of life using validated scales.
- Conditions
- PBC
- Being tested
- Bezafibrate, placebo
- Keywords
- PBC, Bezafibrate
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BezafibrateDrug
placeboDrug
| Study group | Role | What they receive |
|---|---|---|
| Bezafibrate | Experimental | 400 mg/Day Receives: Drug: Bezafibrate |
| Placebo | Placebo comparator | 1 tablet/ day Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of patients with complete biochemical response.
The normalisation of hepatic biochemical tests (aminotransferases (AST, ALT), Alkaline Phosphatase, blood Albumin, blood bilirubin and prothrombin index).
Measured: 24 months
Secondary outcomes (9)
Percentage of patients having biological or clinical adverse reaction.
Increase of ALT, AST or CPK > 5N
Measured: 24 months
Percentage of patients having complete biochemical response.
Percentage of patients having complete biochemical response at Month 12.
Measured: 12 months
Evolution of the pruritus.
Pruritus is measured via visual analogical scale every 3 months from month 0 to month 24
Measured: 24 months
Assessment of the fatigue and the quality of life.
Measured via French questionnaire version of NHP (Nottingham Health Profile) every 12 months from month 0 to month 24
Measured: 24 months
Evolution of liver fibrosis surrogate markers.
assessment of hyaluronic acid serum concentration and hepatic transient elastography (Fibroscan®)
Measured: 24 months
Evolution of the portal hypertension markers.
Occurrence of ascites, decrease in the platelet count below 150000/mm3 or of more than 30% of its initial value, evolution of the ultrasound data of the splanchnic circulation, occurrence or size progression of oesophageal varices (endoscopy)
Measured: 24 months
Histological evolution: Histopathological examination of biological sample before enrolment and at the end of the study.
Quantification of the fibrosis and the inflammatory and destructive injuries.
Measured: 24 months
Evolution of the biological markers of the hepatic function or being in the usual prognostic scores (Mayo, Child, MELD).
Blood albumin, prothrombin time, INR, blood bilirubin, creatinine blood level.
Measured: 24 months
Survival without transplantation and hepatic impairment.
Occurrence of ascites, a digestive variceal bleeding, a hepatic encephalopathy, or a doubling of the total blood bilirubin exceeding the threshold of 50 µmols/L (3 mg/dl).
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2012 (estimated)
- Study start15 Oct 2012
- Primary completion31 Dec 2016
- Study completion31 Dec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for PBCStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Christophe Corpechot, Doctor, Principal investigator, Assistance Publique
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01654731
- Sponsor's protocol ID
- P100109
- Other IDs
- AOM 10291
- Acronym
- BEZURSO
- Status last verified
- Feb 2023
- First submitted
- 30 Jul 2012
- Last updated
- 27 Feb 2023
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Corpechot C, Chazouilleres O, Rousseau A, Le Gruyer A, Habersetzer F, Mathurin P, Goria O, Potier P, Minello A, Silvain C, Abergel A, Debette-Gratien M, Larrey D, Roux O, Bronowicki JP, Boursier J, de Ledinghen V, Heurgue-Berlot A, Nguyen-Khac E, Zoulim F, Ollivier-Hourmand I, Zarski JP, Nkontchou G, Lemoinne S, Humbert L, Rainteau D, Lefevre G, de Chaisemartin L, Chollet-Martin S, Gaouar F, Admane FH, Simon T, Poupon R. A Placebo-Controlled Trial of Bezafibrate in Primary Biliary Cholangitis. N Engl J Med. 2018 Jun 7;378(23):2171-2181. doi: 10.1056/NEJMoa1714519.
PubMed 29874528Corpechot C, Chazouilleres O, Lemoinne S, Rousseau A. Letter: reduction in projected mortality or need for liver transplantation associated with bezafibrate add-on in primary biliary cholangitis with incomplete UDCA response. Aliment Pharmacol Ther. 2019 Jan;49(2):236-238. doi: 10.1111/apt.15049. No abstract available.
PubMed 30589964
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter, Randomized, Double-blind Placebo Controlled Trial of Bezafibrate for the Treatment of Primary Biliary Cirrhosis in Patients With Incomplete Response to Ursodesoxycholic Acid Therapy.
- ClinicalTrials.gov ID
- NCT01654731
- Acronym / sponsor ID
- BEZURSO / P100109
- Conditions
- PBC
- Keywords
- PBC, Bezafibrate
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 15 Oct 2012 (actual)
- Primary completion
- 31 Dec 2016 (actual)
- Study completion
- 31 Dec 2016 (actual)
- First posted
- 1 Aug 2012 (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.
Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease that eventually leads to end-stage liver failure and death unless liver transplantation (LT) is performed. Ursodeoxycholic acid (UDCA) administered orally at the daily dose of 13-15 mg/kg is currently the only drug approved for the treatment of PBC. UDCA consistently improves biochemical liver tests, prolongs survival without LT, and delays histological progression as well as the occurrence of portal hypertension. However, a significant proportion (40%) of patients treated with UDCA shows an incomplete biochemical response and remains at high risk of death or LT. The development of new treatments in combination with UDCA is therefore needed. Several candidates exist among which is Bezafibrate. Bezafibrate belongs to the fibrates' pharmacological class, which has been developed 4 decades ago for the treatment of mixed hyperlipidaemia. Bezafibrate is cheap, widely available and well tolerated. There is now a substantial body of circumstantial evidence supporting that fibrates, and Bezafibrate in particular, are well tolerated and can improve biochemical liver tests in patients with PBC with incomplete response to UDCA. However, despite several positive successful pilot studies, there are still no phase 3 randomized placebo-controlled trials of fibrates for the treatment of PBC. The purpose of this protocol is therefore to conduct such a trial in a selected population of patients with PBC based on an incomplete biochemical response after 6 months of UDCA therapy.
Detailed description
This is a multi-center, randomized (treatment will be assigned by chance), placebo-controlled (an inactive substance will be compared with the test drug to see whether the drug has a real effect), parallel-group (two or more groups of patients will receive different treatments) study that will assess the efficacy and safety of bezafibrate in patients with primary biliary cirrhosis (PBC) who had an inadequate biochemical response to ursodeoxycholic acid, as defined by the Paris II criteria. Bezafibrate 400 mg or placebo will be daily administered in combination with ursodeoxycholic acid (UDCA) 13-15 mg/kg/d for 24 months. Patient safety will be monitored. Primary end-point will be the percentage of patients with a complete normalization of the following biochemical tests: alkaline phosphatase, aminotransferases, total bilirubin, serum albumin, and prothrombin index. Secondary endpoints will include the percentage of drug-related adverse events, survival rates without liver transplantation or liver decompensation, time course of non-invasive liver fibrosis measurements (Fibroscan, serum hyaluronic acid), time course of liver histological parameters (fibrosis stage, necro-inflammatory grade, ductopenia) assessed on percutaneous biopsy specimens, time course of endoscopic, ultrasound, and biochemical features of portal hypertension, time course of pruritus and of quality of life using validated scales.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Bezafibrate | Experimental | Drug: Bezafibrate400 mg/Day |
| Placebo | Placebo comparator | Drug: placebo1 tablet/ day |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age > 18
- Patient with PBC defined by 2 in 3 of the following criteria Positive antimitochondrial antibody type M2. Abnormal serum alkaline phosphatases (ALP > 1,5N) and aminotransferase (AST or ALT > 1N) activities.
- Histological hepatic injuries consistent with PBC from biopsy specimens of at least 10 mm.
- Patient treated with UDCA at the dose of 13 to 15 mg/kg/d (consistent to the AMM)
- Patients showing an incomplete biochemical response to UDCA as defined by : ALP > 1,5N or AST > 1,5N or total bilirubin >17 µmol/l (with conjugated bilirubin > 8 µmol/l) after ≥ 3 months of UDCA at the dose of 13 - 15 mg/kg/day.
Key exclusion criteria (16 listed)
- Unsigned consent.
- Patient with no social insurance or having medical assistant of state
- Ascites or gastrointestinal bleeding (or history of these)
- Serum total bilirubinemia > 50 μmols/L (3 mg/dl) (sample < 3 months)
- Serum albuminemia < 35 g/l (sample < 3 months)
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 |
|---|---|---|
| Bezafibrate | Drug | Bezafibrate |
| placebo | Drug | Placebo |
Primary outcome
Percentage of patients with complete biochemical response.
Time frame: 24 months
The normalisation of hepatic biochemical tests (aminotransferases (AST, ALT), Alkaline Phosphatase, blood Albumin, blood bilirubin and prothrombin index).
9 secondary outcomes
Percentage of patients having biological or clinical adverse reaction.
Time frame: 24 months
Percentage of patients having complete biochemical response.
Time frame: 12 months
Evolution of the pruritus.
Time frame: 24 months
Assessment of the fatigue and the quality of life.
Time frame: 24 months
Evolution of liver fibrosis surrogate markers.
Time frame: 24 months
Evolution of the portal hypertension markers.
Time frame: 24 months
Histological evolution: Histopathological examination of biological sample before enrolment and at the end of the study.
Time frame: 24 months
Evolution of the biological markers of the hepatic function or being in the usual prognostic scores (Mayo, Child, MELD).
Time frame: 24 months
Survival without transplantation and hepatic impairment.
Time frame: 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2023.
- Background: PubMed 29874528Corpechot C, Chazouilleres O, Rousseau A, Le Gruyer A, Habersetzer F, Mathurin P, Goria O, Potier P, Minello A, Silvain C, Abergel A, Debette-Gratien M, Larrey D, Roux O, Bronowicki JP, Boursier J, de Ledinghen V, Heurgue-Berlot A, Nguyen-Khac E, Zoulim F, Ollivier-Hourmand I, Zarski JP, Nkontchou G, Lemoinne S, Humbert L, Rainteau D, Lefevre G, de Chaisemartin L, Chollet-Martin S, Gaouar F, Admane FH, Simon T, Poupon R. A Placebo-Controlled Trial of Bezafibrate in Primary Biliary Cholangitis. N Engl J Med. 2018 Jun 7;378(23):2171-2181. doi: 10.1056/NEJMoa1714519.
- Derived from this study: PubMed 30589964Corpechot C, Chazouilleres O, Lemoinne S, Rousseau A. Letter: reduction in projected mortality or need for liver transplantation associated with bezafibrate add-on in primary biliary cholangitis with incomplete UDCA response. Aliment Pharmacol Ther. 2019 Jan;49(2):236-238. doi: 10.1111/apt.15049. No abstract available.
- ResultsLink provided by the sponsor.
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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.
Christophe Corpechot, Doctor principal investigator
Assistance Publique
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Bezafibrate in people with PBC, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 16 exclusion criteria. 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: finished, as of the sponsor's last update on 27 Feb 2023. 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 France. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Percentage of patients with complete biochemical response. (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01654731, which also lists 2 linked publications.
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 27 Feb 2023.