Obeticholic Acid + Bezafibrate for Primary Biliary Cholangitis

No longer recruiting at 35 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how two investigational drugs, obeticholic acid (OCA) and bezafibrate (BZF), work alone and together for individuals with Primary Biliary Cholangitis (PBC), a liver condition that can cause fatigue and itchy skin. The study includes several groups to compare different doses and combinations of the drugs. Suitable participants have a confirmed diagnosis of PBC and have maintained a stable treatment plan with or without ursodeoxycholic acid (a common medication for PBC) for some time. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that obeticholic acid (OCA) is approved as a secondary treatment for primary biliary cholangitis (PBC) when the initial treatment proves ineffective or causes side effects. This approval indicates that OCA has undergone safety testing and is generally considered safe for individuals with PBC.

Currently, studies are investigating the combination of bezafibrate (BZF) with OCA. However, the safety of this combination remains under investigation. While OCA is approved for PBC, its use with BZF is not yet approved, which may involve unknown risks.

Prospective trial participants should discuss potential side effects with the research team. The team can provide detailed information about what to expect and how they monitor safety during the study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of obeticholic acid (OCA) and bezafibrate (BZF) for treating primary biliary cholangitis (PBC) because it offers a novel approach by targeting different pathways. Unlike standard treatments like ursodeoxycholic acid, which primarily focuses on bile acid regulation, OCA works by activating the farnesoid X receptor, which reduces liver inflammation and fibrosis. Bezafibrate, on the other hand, activates peroxisome proliferator-activated receptors (PPARs), which can also help improve liver function. By combining these mechanisms, the treatment has the potential to provide enhanced therapeutic benefits for PBC patients.

What evidence suggests that this trial's treatments could be effective for Primary Biliary Cholangitis?

Research has shown that the drugs obeticholic acid (OCA) and bezafibrate (BZF) may help treat primary biliary cholangitis (PBC), a liver disease. In this trial, participants will receive different combinations of these drugs. One study found that using these drugs together improved important signs of liver health in PBC patients. Specifically, they helped lower levels of certain substances in the blood that indicate liver damage. Earlier findings also suggest that combining OCA with BZF can help reduce liver inflammation. While the results are promising, more research is needed to confirm these benefits. ^{1 2 4 5 6}

Who Is on the Research Team?

Lynda Szczech, M.D.

Principal Investigator

Intercept Pharmaceuticals, Inc

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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]

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 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]

Citations

1. 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 ...

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

Press Releases Intercept Presents New Data on the Results of OCA-Bezafibrate Combination Therapy in PBC After Six Months of Treatment in Late-Breaking ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05239468

NCT05239468 | Study of OCA in Combination With BZF ... Study to determine the effect of the investigational drug bezafibrate (BZF) alone and in combination with the investigational drug obeticholic acid (OCA) in ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7930359/

Real-world experience with obeticholic acid in patients ... OCA was also effective in patients who had overlap between autoimmune hepatitis and primary biliary cholangitis. Keywords: Cholestasis, Cirrhosis, Overlap PBC- ...

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

S113 Combined Effect of Obeticholic Acid and Bezafibrate ... Obeticholic acid (OCA) and bezafibrate (BZF) have each improved serum biomarkers of primary biliary cholangitis (PBC)–related liver damage. We assessed the ...

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 ...