Primary Sclerosing CholangitisPhase 3BEZASCLERNCT04309773
Efficacy of 24 Month of Bezafibrate in Primary Sclerosing Cholangitis With Persistent Cholestasis Despite Ursodeoxycholic Acid Therapy
A Phase 3 study testing Bezafibrate (400mg) in addition to standard 15-20 mg/kg/jour UDCA therapy in people with Primary Sclerosing Cholangitis and Cholestasis, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
The objectives of this study are to evaluate the effect of bezafibrate treatment compared to placebo on efficacy and safety in patients with primary sclerosing cholangitis (PSC) and persistent cholestasis despite ursodeoxycholic acid therapy Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Primary Sclerosing Cholangitis, Cholestasis
- What is being tested?
- Bezafibrate (400mg) in addition to standard 15-20 mg/kg/jour UDCA therapy
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 104 participants
- Where
- 1 siteFrance
- Study dates
- 6 Apr 2021to Mar 2025
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males or females ≥ 18 and ≤ 75 years
- Large duct PSC verified by retrograde, operative, percutaneous or magnetic resonance cholangiography (MRC) demonstrating intrahepatic and /or extrahepatic biliary duct changes consistent with PSC
- Colonoscopy (already done or scheduled before randomization) within the last 5 years (or within 6 months if IBD is associated to PSC) with neither cancer nor allgrade dysplasia or endoscopy of the ileal reservoir (already done or scheduled before randomization) within the last 2 years in patients with ileo-anal anastomosis
- ALP ≥ 1.5 ULN at baseline
- Treatment with stable dose of UDCA (15-20 mg/kg/d) for ≥ 6 months before inclusion (rounded to the nearest unit, e.g 14.5 mg/kg/d would be 15mg/kg/d).
- Using contraceptive in childbearing women
- Affiliation to a social security system (AME excepted)
- Signed informed consent
Who cannot join
- Child-Pugh score B or C
- Ascites or digestive hemorrhage (or history of)
- Total bilirubin in the last 3 months > 50 μmole/L (3 mg/dl)
- Gilbert syndrome defined as unconjugated bilirubinemia > 12 μmol/L
- Albumin in the last 3 months < ULN (according to the laboratory reference value)
- Prothrombin index in the last 3 months < 70%
Show all 35Show fewer
- Platelets count in the last 3 months < 100000/mm3
- ALT or AST > 5 ULN in the last 3 months
- Prior liver transplantation
- Treatment with a fibrate within the last 3 months inclusion or with a statin at inclusion
- Current active IBD defined as either current use of systemic corticosteroid therapy > 10 mg/day or budesonide > 3 mg /day or immunosuppressive drugs (cyclosporine, tacrolimus, mycophenolate mofetil, mTor inhibitors, JAK inhibitors) or a partial Mayo score > 2 in patients with ulcerative colitis (UC) or a Crohn's Disease Activity Index (CDAI) > 150 in patients with Crohn's disease (CD)
- Dose change of treatment for associated IBD ≤3 months prior to inclusion
- Current or history of colonic cancer or all-grade dysplasia described at the last colonoscopy (Patients with a history of colon cancer and treated by total colectomy without recurrence for at least 5 years are eligible)
- Any other cause of liver damage ((positive test for HBV, HCV, or HIV, excessive alcohol consumption, hemochromatosis, Wilson's disease, α1-antitrypsin deficiency, celiac disease, autoimmune hepatitis defined by the presence of at least 2 of the 3 following criteria; 1) AST or ALT > 5 ULN, 2) Positive anti smooth muscle auto antibodies or serum IgG > 1.5 ULN, 3) interface hepatitis on liver biopsy)
- Secondary causes of sclerosing cholangitis including IgG4-associated cholangitis (elevated serum IgG4 > 4 ULN)
- History of acute cholangitis in the last 3 months prior to inclusion or current acute cholangitis
- Endoscopic treatment for bile duct stenosis ≤ 3 months prior to inclusion or planned within 3 months post randomization date
- History of or established or suspected hepatobiliary carcinoma.
- Any severe comorbidity that may reduce life expectancy
- History of malignancy diagnosed or treated within 2 years (recent localized treatment of squamous or non-invasive basal skin cancers is permitted; cervical carcinoma in situ is allowed if appropriately treated prior to Screening)
- Known hypersensitivity to bezafibrate, any of the components of Befizal© or other fibrates
- Known photosensitivity or photoallergy reactions to fibrate
- Patient with congenital galactosemia, glucose malabsorption, or lactase deficiency because of presence of lactose in 400 mg SR tablets of bezafibrate and in placebo tablets
- Pregnancy (or desire for)
- Renal insufficiency (clearance < 60 ml/min or serum creatinine level > 130 μmole/L)
- Breastfeeding
- Participation in any other interventional study or in the exclusion period any other interventional study
- Autoimmune hepatitis defined by the presence of interface hepatitis documented on liver biopsy and at least 1 of the 2 following criteria: 1) AST or ALT > 5 ULN, 2) Positive anti smooth muscle auto antibodies or serum IgG > 1.5 ULN
- Results of colonoscopy not available or > 5 years (or > 6 months if IBD is associated to PSC) or with cancer or all-grade dysplasia or results of endoscopy of the ileal reservoir not available or > 2 years in patients with ileo-anal anastomosis
- Randomization exclusion criteria:
- Positive test for HBV (positive HBs Ag), HCV (positive HCV RNA), or HIV (positive serology)
- Pregnancy (or desire for in the 2 next years)
- Secondary causes of sclerosing cholangitis including IgG4-associated cholangitis (elevated serum IgG4 > 4 ULN)
- Autoimmune hepatitis defined by the presence of interface hepatitis documented on liver biopsy and at least 1 of the 2 following criteria: 1) AST or ALT > 5 ULN, 2) Positive anti smooth muscle auto antibodies or serum IgG > 1.5 ULN
- Current acute cholangitis
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
Hepatology department - Hopital Saint Antoine
Paris, 75012
Olivier CHAZOUILLERES, Pr, + 33 (0) 1 49 28 23 80, olivier.chazouilleres@aphp.fr
Christophe Corpechot, Doctor, + 33 (0) 1 49 28 28 36, christophe.corpechot@aphp.fr
About this study
Official title: Double Blind, Multicentric, Randomized, Placebo-controlled Trial, Evaluating the Efficacy of 24 Month of Bezafibrate in Primary Sclerosing Cholangitis With Persistent Cholestasis Despite Ursodeoxycholic Acid Therapy
The objectives of this study are to evaluate the effect of bezafibrate treatment compared to placebo on efficacy and safety in patients with primary sclerosing cholangitis (PSC) and persistent cholestasis despite ursodeoxycholic acid therapy
Read the detailed description
This is a Phase 3, randomized, double-blind, placebo-controlled, evaluation of the efficacy and safety of Bezafibrate in subjects with PSC and persistent cholestasis despite ursodeoxycholic acid therapy (UADC).
Design:
- A multicentre, double-blind placebo controlled, randomised clinical trial
- 35 centers participants to the recruitment (French Network of Reference and Competence Centers for Rare Diseases: "inflammatory biliary diseases and autoimmune hepatitis" (MIVBH), including Saint-Antoine hospital, Paris as reference coordinator center)
Sample size :
104 patients, 52 in each group
Treatments groups:
- UADC therapy (15-20 mg/kg/d) + Bezafibrate (400mg/d)
- UDCA therapy (15-20 mg/kg/d) + placebo of bezafibrate (400mg/d)
Treatments duration :
24 months
Assessement:
Study visits at Inclusion, (M0) Randomisation and then every 3 months until M24
This is a phase III randomized, double blinded, multicenter, study.
No interim analysis is planned. Analysis will be performed at the end of the study after data review and freezing of data base according to intent to treat principle.
- Conditions
- Primary Sclerosing Cholangitis, Cholestasis
- Being tested
- Bezafibrate (400mg) in addition to standard 15-20 mg/kg/jour UDCA therapy, Placebo of Bezafibrate in addition to standard UDCA therapy
- Keywords
- Primary sclerosing cholangitis, Persistent cholestasis, Bezafibrates, Fibrates, UDCA
- Medical subject headings
- Cholangitis, Sclerosing, Cholestasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bezafibrate (400mg) in addition to standard 15-20 mg/kg/jour UDCA therapyDrug
Bezafibrate (400mg) in addition to standard 15-20 mg/kg/jour UDCA therapy Treatment duration : 24 months Bezafibrate/AUDC : daily oral dose
Placebo of Bezafibrate in addition to standard UDCA therapyDrug
Placebo of Bezafibrate (400mg) in addition to standard 15-20 mg/kg/Day UDCA therapy Treatment duration : 24 months Placebo/AUDC : daily oral dose
| Study group | Role | What they receive |
|---|---|---|
| Bezafibrate in addition to standard UDCA therapy | Experimental | Bezafibrate (400mg) in addition to standard 15-20 mg/kg/day UDCA therapy ("experimental" arm) Receives: Drug: Bezafibrate (400mg) in addition to standard 15-20 mg/kg/jour UDCA therapy |
| Placebo of Bezafibrate in addition to standard UDCA therapy | Placebo comparator | Placebo of Bezafibrate in addition to standard 15-20 mg/kg/day UDCA therapy Receives: Drug: Placebo of Bezafibrate in addition to standard UDCA therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the efficacy of 24-month treatment with bezafibrate (400 mg/day) versus placebo in addition to standard UDCA therapy in Primary Sclerosing Cholangitis (PSC).
Proportion of patients with serum Alkaline Phosphatase < 1.5 ULN and a reduction of at least 15% from baseline at M24 and normal serum bilirubin and no increase of liver stiffness at M24 compared to baseline:
Measured: At 24 months
Secondary outcomes (6)
Percentage of patients with clinical or biological adverse events
Safety endpoint: Percentage of patients with clinical (including increased IBD activity) or biological adverse events (elevated creatinine (> 150 μmol/L) or ALT (> 5ULN) or AST (> 5ULN) or CPK (> 5ULN) during the study period.
Measured: At 24 months
Quality of life of PSC patients
French version of the quality of life QMCF questionnaire.
Measured: At 12 months and 24 months
Score for pruritus
Absolute changes in the score for pruritus (measured by VAS and 5D pruritus scale) at each study visit.
Measured: At 12 months and 24 months
Fatigue score
Absolute changes in the score for fatigue (measured by adapted PBC-40 questionnaire)
Measured: At 12 months and 24 months
Level of liver biochemical parameters between the two groups of patient
The course during the study will be studied using linear regression mixed model.
A random effect for each patient will be considered and treatment group will be considered as fixed effects.
Measured: between month 0 and month 24
Occurrence of clinical events and transplant-free survival
Survival rate without liver transplantation or hepatic events (ascites, variceal bleeding, encephalopathy, acute cholangitis, cholangiocarcinoma, hepatocellular carcinoma or serum total bilirubin > 100 μmol/L for at least 3 months).
Measured: At 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2020
- Study start6 Apr 2021
- Primary completionMar 2023 (estimated)
- Study completionMar 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary Sclerosing CholangitisStudies 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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 104 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Olivier CHAZOUILLERES, professor, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04309773
- Sponsor's protocol ID
- APHP180668
- Acronym
- BEZASCLER
- Status last verified
- May 2022
- First submitted
- 18 Oct 2019
- Last updated
- 10 May 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Double Blind, Multicentric, Randomized, Placebo-controlled Trial, Evaluating the Efficacy of 24 Month of Bezafibrate in Primary Sclerosing Cholangitis With Persistent Cholestasis Despite Ursodeoxycholic Acid Therapy
- ClinicalTrials.gov ID
- NCT04309773
- Acronym / sponsor ID
- BEZASCLER / APHP180668
- Conditions
- Primary Sclerosing Cholangitis, Cholestasis
- Keywords
- Primary sclerosing cholangitis, Persistent cholestasis, Bezafibrates, Fibrates, UDCA
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 104 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 6 Apr 2021 (actual)
- Primary completion
- Mar 2023 (estimated)
- Study completion
- Mar 2025 (estimated)
- First posted
- 16 Mar 2020 (actual)
- 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.
The objectives of this study are to evaluate the effect of bezafibrate treatment compared to placebo on efficacy and safety in patients with primary sclerosing cholangitis (PSC) and persistent cholestasis despite ursodeoxycholic acid therapy
Detailed description
This is a Phase 3, randomized, double-blind, placebo-controlled, evaluation of the efficacy and safety of Bezafibrate in subjects with PSC and persistent cholestasis despite ursodeoxycholic acid therapy (UADC).
Design:
- A multicentre, double-blind placebo controlled, randomised clinical trial
- 35 centers participants to the recruitment (French Network of Reference and Competence Centers for Rare Diseases: "inflammatory biliary diseases and autoimmune hepatitis" (MIVBH), including Saint-Antoine hospital, Paris as reference coordinator center)
Sample size :
104 patients, 52 in each group
Treatments groups:
- UADC therapy (15-20 mg/kg/d) + Bezafibrate (400mg/d)
- UDCA therapy (15-20 mg/kg/d) + placebo of bezafibrate (400mg/d)
Treatments duration :
24 months
Assessement:
Study visits at Inclusion, (M0) Randomisation and then every 3 months until M24
This is a phase III randomized, double blinded, multicenter, study.
No interim analysis is planned. Analysis will be performed at the end of the study after data review and freezing of data base according to intent to treat principle.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Bezafibrate in addition to standard UDCA therapy | Experimental | Drug: Bezafibrate (400mg) in addition to standard 15-20 mg/kg/jour UDCA therapyBezafibrate (400mg) in addition to standard 15-20 mg/kg/day UDCA therapy ("experimental" arm) |
| Placebo of Bezafibrate in addition to standard UDCA therapy | Placebo comparator | Drug: Placebo of Bezafibrate in addition to standard UDCA therapyPlacebo of Bezafibrate in addition to standard 15-20 mg/kg/day UDCA therapy |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Males or females ≥ 18 and ≤ 75 years
- Large duct PSC verified by retrograde, operative, percutaneous or magnetic resonance cholangiography (MRC) demonstrating intrahepatic and /or extrahepatic biliary duct changes consistent with PSC
- Colonoscopy (already done or scheduled before randomization) within the last 5 years (or within 6 months if IBD is associated to PSC) with neither cancer nor allgrade dysplasia or endoscopy of the ileal reservoir (already done or scheduled before randomization) within the last 2 years in patients with ileo-anal anastomosis
- ALP ≥ 1.5 ULN at baseline
- Treatment with stable dose of UDCA (15-20 mg/kg/d) for ≥ 6 months before inclusion (rounded to the nearest unit, e.g 14.5 mg/kg/d would be 15mg/kg/d).
Key exclusion criteria (35 listed)
- Child-Pugh score B or C
- Ascites or digestive hemorrhage (or history of)
- Total bilirubin in the last 3 months > 50 μmole/L (3 mg/dl)
- Gilbert syndrome defined as unconjugated bilirubinemia > 12 μmol/L
- Albumin in the last 3 months < ULN (according to the laboratory reference value)
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 (400mg) in addition to standard 15-20 mg/kg/jour UDCA therapyBezafibrate (400mg) in addition to standard 15-20 mg/kg/jour UDCA therapy Treatment duration : 24 months Bezafibrate/AUDC : daily oral dose | Drug | Bezafibrate in addition to standard UDCA therapy |
| Placebo of Bezafibrate in addition to standard UDCA therapyPlacebo of Bezafibrate (400mg) in addition to standard 15-20 mg/kg/Day UDCA therapy Treatment duration : 24 months Placebo/AUDC : daily oral dose | Drug | Placebo of Bezafibrate in addition to standard UDCA therapy |
Primary outcome
To assess the efficacy of 24-month treatment with bezafibrate (400 mg/day) versus placebo in addition to standard UDCA therapy in Primary Sclerosing Cholangitis (PSC).
Time frame: At 24 months
Proportion of patients with serum Alkaline Phosphatase < 1.5 ULN and a reduction of at least 15% from baseline at M24 and normal serum bilirubin and no increase of liver stiffness at M24 compared to baseline:
6 secondary outcomes
Percentage of patients with clinical or biological adverse events
Time frame: At 24 months
Quality of life of PSC patients
Time frame: At 12 months and 24 months
Score for pruritus
Time frame: At 12 months and 24 months
Fatigue score
Time frame: At 12 months and 24 months
Level of liver biochemical parameters between the two groups of patient
Time frame: between month 0 and month 24
Occurrence of clinical events and transplant-free survival
Time frame: At 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2022.
- 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.
Olivier CHAZOUILLERES, professor principal investigator
Assistance Publique - Hôpitaux de Paris
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 (400mg) in addition to standard 15-20 mg/kg/jour UDCA therapy in people with Primary Sclerosing Cholangitis and Cholestasis, 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 8 inclusion and 35 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: status not confirmed, as of the sponsor's last update on 10 May 2022. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Olivier CHAZOUILLERES, professor (+ 33149282380, olivier.chazouilleres@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To assess the efficacy of 24-month treatment with bezafibrate (400 mg/day) versus placebo in addition to standard UDCA therapy in Primary Sclerosing Cholangitis (PSC). (time frame: At 24 months). 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 10 May 2022.