Obeticholic Acid + Bezafibrate for Primary Biliary Cirrhosis

No longer recruiting at 60 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Intercept Pharmaceuticals

Must be taking: Investigational product

Disqualifiers: Other liver diseases, Gallbladder disease, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 60 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to assess the safety and tolerability of a combination of two drugs, Obeticholic Acid and Bezafibrate, for individuals with Primary Biliary Cholangitis (PBC), a disease that gradually destroys the liver's bile ducts. Participants will take both drugs in a single daily tablet to evaluate long-term effects. The trial is open to individuals with PBC who are already part of certain ongoing studies. As a Phase 3 trial, it represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It might be best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Previous studies have generally found the combination of obeticholic acid and bezafibrate to be well-tolerated. Research shows that this combination may improve health markers without causing serious side effects. Although still under study, past results suggest it is safe. Mild discomfort or side effects are common, but serious problems have not been widely reported in research so far. It is important to consult a healthcare provider to understand the potential risks and benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for primary biliary cirrhosis?

Most treatments for Primary Biliary Cirrhosis focus on managing symptoms and slowing disease progression, often through medications like ursodeoxycholic acid (UDCA) or obeticholic acid alone. However, this new combination treatment is unique because it pairs obeticholic acid with bezafibrate, potentially enhancing the therapeutic effects. Researchers are excited about this combination because it targets two different pathways in the liver, which could lead to better outcomes by more effectively reducing liver inflammation and damage. This dual-action approach offers hope for improved efficacy compared to current single-agent therapies.

What evidence suggests that this treatment might be an effective treatment for primary biliary cirrhosis?

Research has shown that using obeticholic acid (OCA) and bezafibrate (BZF) together can effectively treat primary biliary cholangitis (PBC), a liver disease. In this trial, participants will receive a fixed-dose combination of OCA 5 mg and BZF 400 mg SR once daily. Studies have found that this drug combination can improve several blood markers, which are linked to better liver health and a reduced need for liver transplants. Previous evidence suggests that using both drugs together improves liver function more than using just one of them. Overall, this combination treatment has shown promising results for patients with PBC. ^{2 4 5 6 7}

Who Is on the Research Team?

Lynda Szczech, PhD

Principal Investigator

Intercept Pharmaceuticals Inc.

Are You a Good Fit for This Trial?

This trial is for individuals who have Primary Biliary Cholangitis (PBC) and are currently participating in either Study 747-213 or Study 747-214. It's designed to assess the long-term safety of a combined medication.

Inclusion Criteria

All subjects with PBC who participated and are actively taking investigational product in Study 747-213 or Study 747-214 are eligible to enroll in this study (977-311)

Exclusion Criteria

I have or had other liver diseases.

I have had liver failure or similar serious liver problems.

I am experiencing complications from primary biliary cholangitis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a fixed-dose combination of Obeticholic Acid and Bezafibrate once daily

Up to 60 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants continue to receive the study medication to evaluate long-term safety and tolerability

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Fixed-Dose Combination of Obeticholic Acid and Bezafibrate

Trial Overview The study tests a fixed-dose combination tablet containing Obeticholic Acid (5 mg) and Bezafibrate (400 mg). The goal is to understand how safe and tolerable this medication is over an extended period for PBC patients.

How Is the Trial Designed?

Group I: OCA 5 mg + BZF 400 mg SR Experimental Treatment 1 Intervention

Participants will be administered with OCA 5 mg + BZF 400 mg SR once daily.

Who Is Running the Clinical Trial?

Intercept Pharmaceuticals

Lead Sponsor

Trials

29

Recruited

16,600+

Published Research Related to This Trial

In a study of 351 patients with primary biliary cholangitis, treatment with obeticholic acid (OCA) or fibrates significantly improved liver enzyme levels and the GLOBE score, indicating better liver health.

Adverse events occurred in 14.7% of patients, with the most common being pruritus, and treatment discontinuation was more frequent with fenofibrate due to intolerance, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obeticholic Acid and Fibrates in Primary Biliary Cholangitis: Comparative Effects in a Multicentric Observational Study. Reig, A., Álvarez-Navascués, C., Vergara, M., et al.[2021]

In a study of 100 cirrhotic patients with primary biliary cholangitis (PBC) treated with obeticholic acid (OCA), only about one-third achieved a biochemical response after 6 and 12 months, indicating limited efficacy in this population.

Key risk factors for serious adverse events (SAEs) during OCA therapy included high bilirubin levels (≥1.4 mg/dl), lower albumin levels, and a higher Child-Pugh score, suggesting that careful baseline assessments are essential to identify patients who may not safely benefit from OCA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of serious adverse events and non-response in cirrhotic patients with primary biliary cholangitis treated with obeticholic acid. De Vincentis, A., D'Amato, D., Cristoferi, L., et al.[2023]

Obeticholic acid (OCA) significantly reduced alkaline phosphatase (ALP) levels in patients with primary biliary cirrhosis who did not respond adequately to ursodeoxycholic acid, with reductions of 21%-25% compared to only 3% in the placebo group over 3 months.

The treatment was effective across all doses (10 mg, 25 mg, and 50 mg), but the 10 mg dose had the lowest incidence of pruritus, a common side effect, while maintaining significant biochemical improvements, which were sustained in a 12-month extension study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of obeticholic acid in patients with primary biliary cirrhosis and inadequate response to ursodeoxycholic acid. Hirschfield, GM., Mason, A., Luketic, V., et al.[2022]

The multicentric observational study compared the effects of obeticholic acid and fibrates in patients with primary biliary cholangitis, highlighting their efficacy in managing this liver disease.

Results indicated that obeticholic acid may provide superior benefits in improving liver function tests compared to fibrates, suggesting it could be a more effective treatment option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuing Medical Education Questions: November 2021. Richter, SJ.[2023]

Citations

1. interceptpharma.com interceptpharma.com/about-us/news/?id=2894098

Press Releases Results show combination of OCA 5-10 mg and bezafibrate 400 mg normalizes multiple serum biomarkers that are associated with improved transplant-free and ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04594694

NCT04594694 | Study of OCA in Combination With BZF ... Study to evaluate the efficacy, safety, and tolerability of investigational drug obeticholic acid (OCA) in combination with the investigational drug bezafibrate ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6686091/

Effectiveness of bezafibrate and ursodeoxycholic acid in ... UDCA and bezafibrate combined treatment is superior to UDCA alone in UDCA non-responders with regard to decreasing liver biochemistry markers, without any ...

4. ddw.digitellinc.com ddw.digitellinc.com/p/s/metabolic-outcomes-and-key-efficacy-data-from-a-phase-2-trial-evaluating-combination-obeticholic-acid-and-bezafibrate-in-patients-with-primary-biliary-cholangitis-6499

METABOLIC OUTCOMES AND KEY EFFICACY DATA FROM ... METABOLIC OUTCOMES AND KEY EFFICACY DATA FROM A PHASE 2 TRIAL EVALUATING COMBINATION OBETICHOLIC ACID AND BEZAFIBRATE IN PATIENTS WITH PRIMARY BILIARY ...

5. gut.bmj.com gut.bmj.com/content/74/Suppl_4/A41.2

P44 Combination of obeticholic acid with bezafibrate ... O9 Results from a planned interim analysis of a randomized, double-blind, active-controlled trial evaluating the effects of obeticholic acid and bezafibrate on ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06488911

Study Details | NCT06488911 | To Evaluate Safety and ... An Open Label Long-Term Study to Evaluate the Safety and Tolerability of the Fixed-Dose Combination (FDC) of Obeticholic Acid (OCA) and Bezafibrate (BZF) tablet ...

7. journals.lww.com journals.lww.com/10.14309/01.ajg.0001028820.02913.42

S113 Combined Effect of Obeticholic Acid and Bezafibrate ... OCA + BZF is generally well tolerated and has therapeutic potential to normalize serum biomarkers associated with improved transplant-free and decompensation- ...