Obeticholic Acid + Bezafibrate for Primary Biliary Cholangitis

Recruiting at 25 trial locations

Overseen By Erminia Cafasso

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Intercept Pharmaceuticals

Must be taking: Ursodeoxycholic acid

Must not be taking: Obeticholic acid, Fibrates

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

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

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

Compensation: Varies

Number of Visits: Unknown

60 Participants Needed

Trial Summary

What is the purpose of this trial?

Study to determine the effect of the investigational drug bezafibrate (BZF) alone and in combination with the investigational drug obeticholic acid (OCA) in participants with Primary Biliary Cholangitis (PBC).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must not have taken certain medications like obeticholic acid, fibrates, or similar drugs within 3 months before the trial starts.

What data supports the effectiveness of the drug combination of Obeticholic Acid and Bezafibrate for Primary Biliary Cholangitis?

Research shows that combining Obeticholic Acid and Bezafibrate can improve liver function tests in patients with Primary Biliary Cholangitis who do not respond well to the standard treatment, Ursodeoxycholic Acid. This combination has been effective in normalizing biochemical liver tests in difficult-to-treat cases. ^{1 2 3 4 5}

Is the combination of Obeticholic Acid and Bezafibrate safe for humans?

Research shows that Obeticholic Acid and Bezafibrate have been used as treatments for primary biliary cholangitis, and while they can improve liver function, there is limited information on their safety outside of clinical trials. Some studies have evaluated their safety and effectiveness, but more real-world data is needed to fully understand their safety profile. ^{2 3 4 5 6}

How is the drug combination of Obeticholic Acid and Bezafibrate unique for treating primary biliary cholangitis?

The combination of Obeticholic Acid and Bezafibrate is unique because it is used as a second-line treatment for patients with primary biliary cholangitis who do not respond adequately to the standard treatment, ursodeoxycholic acid. This combination has shown the ability to improve liver function tests in difficult-to-treat cases. ^{1 2 3 4 5}

Research Team

Lynda Szczech, M.D.

Principal Investigator

Intercept Pharmaceuticals, Inc

Eligibility Criteria

This trial is for people with Primary Biliary Cholangitis (PBC) who have been on a drug called UDCA for at least a year, or not at all in the past 3 months. It's not open to pregnant or breastfeeding women, those who can't handle bezafibrate, have other liver diseases, gallbladder disease, or were recently in fibrate/OCA studies.

Inclusion Criteria

I have been diagnosed with primary biliary cholangitis.

Qualifying ALP and/or bilirubin liver biochemistry values

I have been on UDCA for 12 months or haven't taken it for 3 months.

Exclusion Criteria

I cannot tolerate fibrates or have not taken them in the last 3 months.

I haven't taken OCA or similar drugs in the last 3 months.

I have or had gallbladder disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double Blind (DB) Phase

Participants receive either BZF alone or in combination with OCA in a double-blind manner

12 weeks

Regular visits as per protocol

Long Term Safety Extension (LTSE) Phase

Participants may continue treatment with OCA and BZF to assess long-term safety

Long-term

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Bezafibrate
• Obeticholic Acid

Trial Overview The study tests bezafibrate (BZF), alone and combined with obeticholic acid (OCA), against placebos to see their effects on PBC. Participants will receive either BZF at different doses or OCA along with dummy pills to compare results.

Participant Groups

Group I: Long Term Safety Extension (LTSE) Phase Treatment D of the DB phase: OCA 5 mg + BZF 400 mg IR Experimental Treatment 2 Interventions

Each participant will take one OCA 5 mg tablet and two BZF 200 mg IR tablets (to achieve 400 mg dose) daily.

Group II: Double Blind (DB) Phase Treatment D: OCA 5 mg + BZF 400 mg IR Experimental Treatment 2 Interventions

Each participant will take one OCA 5 mg tablet and two BZF 200 mg IR tablets (to achieve 400 mg dose) daily.

Group III: Double Blind (DB) Phase Treatment C: OCA 5 mg + BZF 100 mg IR Experimental Treatment 3 Interventions

Each participant will take one OCA 5 mg tablet, one BZF 100 mg IR tablet and one BZF placebo tablet, daily.

Group IV: Double Blind (DB) Phase Treatment A: BZF 100 milligrams (mg) Immediate Release (IR) tablet Active Control 3 Interventions

Each Participant will take one OCA placebo tablet, one BZF 100 mg IR tablet and one BZF placebo tablet daily.

Group V: Double Blind (DB) Phase Treatment B: BZF 400 mg IR tablet Active Control 2 Interventions

Each Participant will take one OCA placebo tablet and two BZF 200 mg IR tablets (to achieve 400 mg dose) daily.

Who Is Running the Clinical Trial?

Intercept Pharmaceuticals

Lead Sponsor

Trials

29

Recruited

16,600+

Findings from Research

Combining ursodeoxycholic acid (UDCA) with bezafibrate significantly improves liver biochemistry markers in patients with primary biliary cholangitis (PBC) who do not respond adequately to UDCA alone, based on a meta-analysis of 10 trials involving 369 patients.

The combination therapy effectively reduces levels of alanine aminotransferase, alkaline phosphatase, and other liver-related markers without increasing the risk of adverse effects compared to UDCA monotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of bezafibrate and ursodeoxycholic acid in patients with primary biliary cholangitis: a meta-analysis of randomized controlled trials. Agrawal, R., Majeed, M., Attar, BM., et al.[2022]

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 457 patients with primary biliary cholangitis, obeticholic acid (OCA) showed a significant reduction in alkaline phosphatase levels by 29.5% after 12 months, while fibric acid derivatives achieved a higher reduction of 56.7%.

Despite the differences in alkaline phosphatase reduction, the overall biochemical response rates were similar between OCA (70.6%) and fibric acid treatments (80%), indicating that both therapies are effective second-line options for patients who do not respond adequately to ursodeoxycholic acid.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

UK-Wide Multicenter Evaluation of Second-line Therapies in Primary Biliary Cholangitis. Abbas, N., Culver, EL., Thorburn, D., et al.[2023]

Obeticholic acid (Ocaliva) is an FXR agonist that has received accelerated approval in the USA for treating primary biliary cholangitis, particularly in patients who do not respond adequately to ursodeoxycholic acid or cannot tolerate it.

The drug is currently in preregistration for the same indication in the EU, highlighting its potential as a significant treatment option for liver diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obeticholic Acid: First Global Approval. Markham, A., Keam, SJ.[2018]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Determinants of the effectiveness of bezafibrate combined with ursodeoxycholic acid in patients with primary biliary cholangitis. [2023]

2. Greece pubmed.ncbi.nlm.nih.gov

Effectiveness of bezafibrate and ursodeoxycholic acid in patients with primary biliary cholangitis: a meta-analysis of randomized controlled trials. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Combination of fibrates with obeticholic acid is able to normalise biochemical liver tests in patients with difficult-to-treat primary biliary cholangitis. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Obeticholic Acid and Fibrates in Primary Biliary Cholangitis: Comparative Effects in a Multicentric Observational Study. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

UK-Wide Multicenter Evaluation of Second-line Therapies in Primary Biliary Cholangitis. [2023]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Obeticholic Acid: First Global Approval. [2018]