Pemafibrate for Primary Biliary Cirrhosis

Not currently recruiting at 39 trial locations

Overseen By Director, Clinical Operations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Kowa Research Institute, Inc.

Disqualifiers: Hepatitis C, Hepatitis B, Alcoholic liver disease, Autoimmune hepatitis, NASH, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests pemafibrate, a new treatment, to evaluate its effectiveness and safety for individuals with primary biliary cirrhosis (PBC), a liver disease that damages bile ducts. Participants will receive one of two doses of pemafibrate or a placebo (a non-active treatment) for a certain period, followed by pemafibrate. The trial aims to determine if different doses can help manage PBC symptoms. Individuals diagnosed with PBC and who have had high alkaline phosphatase (a liver enzyme) levels for at least 6 months might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that pemafibrate is generally safe for people with liver conditions. Studies have found that using pemafibrate alongside other common treatments can improve key liver health indicators like ALP, GGT, and bilirubin, which measure liver function.

One study found that pemafibrate might help when standard treatments aren't enough. It improved liver function without causing serious side effects, suggesting it could be safe for long-term use in treating liver problems.

Although this trial is in its early stages, existing research offers promising signs about the safety of pemafibrate for liver conditions. Participants in previous studies did not report significant negative effects, which is encouraging for those considering joining a clinical trial. ^{1 2 3 4 5}

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

Researchers are excited about pemafibrate for primary biliary cirrhosis because it offers a new way to manage the disease by targeting a different mechanism than current treatments like ursodeoxycholic acid and obeticholic acid. Pemafibrate is a selective peroxisome proliferator-activated receptor alpha (PPARα) modulator, which helps regulate lipid metabolism and reduce inflammation in the liver. This unique approach not only has the potential to improve liver function but also may offer better tolerability and fewer side effects compared to existing options.

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

This trial will evaluate pemafibrate's effectiveness for patients with primary biliary cholangitis (PBC). Studies have shown that pemafibrate can benefit patients with PBC, particularly those who don't respond well to the usual treatment, ursodeoxycholic acid (UDCA). Research indicates that pemafibrate improves liver health by lowering levels of ALP, GGT, and bilirubin, which are important markers of liver function. In patients with PBC and high blood fat levels, pemafibrate has shown positive results when other treatments were insufficient. Additionally, it has improved liver health and overall well-being in patients. These findings suggest that pemafibrate could be a promising option for better managing PBC. ^{1 2 3 4 6}

Who Is on the Research Team?

Andre Belous, MD, PhD

Principal Investigator

Kowa Pharma Development Co.

Are You a Good Fit for This Trial?

This trial is for people with Primary Biliary Cholangitis (PBC) who haven't had enough improvement with standard treatments like Ursodeoxycholic Acid or Obeticholic Acid. Specific eligibility details are not provided, but typically participants must meet certain health standards and may be excluded based on other medical conditions.

Inclusion Criteria

Participant has ALP ≥1.5 × ULN

Participant meets all other eligibility criteria outlined in the Clinical Study Protocol

Male or female participant with a PBC diagnosis demonstrated by the presence of ≥2 of the following three diagnostic criteria: History of ALP above ULN for at least 6 months, History of positive antimitochondrial antibody (AMA) titer or positive PBC-specific antinuclear antibody (ANA) titer, Historical liver biopsy consistent with PBC

Exclusion Criteria

Participant has Gilbert's Syndrome

I have been diagnosed with Alpha-1-antitrypsin deficiency, cystic fibrosis, Wilson's disease, or hemochromatosis.

I have a liver condition known as sclerosing cholangitis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either K-808 (Pemafibrate) or placebo for 12 weeks

12 weeks

Extension

Participants who received placebo switch to K-808 (Pemafibrate) for 52 weeks

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pemafibrate

Trial Overview

The study is testing the effectiveness and safety of two different doses of a drug called K-808 (pemafibrate) compared to a placebo. Participants will randomly receive either one of the K-808 doses or a placebo to see if there's an improvement in their PBC symptoms.

How Is the Trial Designed?

Group I: K-808 Group B Experimental Treatment 1 Intervention

K-808 (Dose B) for 64 Weeks

Group II: K-808 Group A Experimental Treatment 1 Intervention

K-808 (Dose A) for 64 Weeks

Group III: Placebo + K-877 (Group B) Placebo Group 2 Interventions

Placebo for 12 Weeks followed by K-808 (Dose B) for 52 Weeks

Group IV: Placebo + K-877 (Group A) Placebo Group 2 Interventions

Placebo for 12 Weeks followed by K-808 (Dose A) for 52 Weeks

Pemafibrate is already approved in Japan for the following indications:

Approved in Japan as Parmodia for:

• Hyperlipidaemia
• Familial hyperlipidaemia

Who Is Running the Clinical Trial?

Kowa Research Institute, Inc.

Lead Sponsor

Trials

46

Recruited

16,400+

Published Research Related to This Trial

In a study of patients with primary biliary cholangitis (PBC) and dyslipidemia, pemafibrate (PEM) significantly improved alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) levels in 87% of patients when added to ursodeoxycholic acid (UDCA) treatment.

Switching from bezafibrate to PEM in patients already on UDCA and bezafibrate resulted in improved kidney function (eGFR and creatinine levels), although only about 52% showed improvement in ALP and GGT, indicating that PEM can be beneficial for those with renal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of pemafibrate on primary biliary cholangitis with dyslipidemia. Yamaguchi, M., Asano, T., Arisaka, T., et al.[2022]

In a study of 1,121 patients with primary biliary cirrhosis (PBC) treated with bezafibrate alongside ursodeoxycholic acid (UDCA), normalizing alanine transaminase (ALT) levels significantly reduced the risk of developing liver-related symptoms over an average follow-up of 6.1 years.

The findings suggest that bezafibrate can be an effective addition for patients with PBC who do not respond adequately to UDCA, as achieving normal ALT levels was associated with outcomes similar to those of patients receiving UDCA alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biochemical responses to bezafibrate improve long-term outcome in asymptomatic patients with primary biliary cirrhosis refractory to UDCA. Tanaka, A., Hirohara, J., Nakanuma, Y., et al.[2021]

In a study of 22 patients with primary biliary cirrhosis (PBC) who were not responding to UDCA alone, the combination therapy of UDCA and bezafibrate significantly reduced serum alkaline phosphatase (ALP) levels compared to UDCA monotherapy.

At the end of the 6-month treatment, 45.4% of patients receiving the combination therapy achieved normalization of ALP levels, suggesting that this combination may be an effective new treatment option for PBC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bezafibrate treatment: a new medical approach for PBC patients? Kanda, T., Yokosuka, O., Imazeki, F., et al.[2022]

In a pilot study involving 30 women with primary biliary cirrhosis (PBC) who had suboptimal responses to ursodeoxycholic acid (UDCA), the addition of bezafibrate significantly reduced alkaline phosphatase levels within just 3 months, indicating improved liver function.

Bezafibrate treatment also led to improvements in other liver enzymes and symptoms like pruritus, with no severe adverse effects reported, suggesting it is a safe and effective adjunct therapy for patients with early-stage PBC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bezafibrate normalizes alkaline phosphatase in primary biliary cirrhosis patients with incomplete response to ursodeoxycholic acid. Lens, S., Leoz, M., Nazal, L., et al.[2022]

Seladelpar has shown significant improvements in liver biochemistry and may alleviate symptoms in patients with primary biliary cholangitis (PBC), suggesting it could be an effective treatment option.

Safety concerns regarding liver toxicity associated with seladelpar appear to have been resolved, making it a promising candidate for use as a second-line therapy in PBC compared to existing off-label fibrates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Seladelpar: an investigational drug for the treatment of early-stage primary biliary cholangitis (PBC). Wetten, A., Jones, DEJ., Dyson, JK.[2023]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/35072975/

Effects of pemafibrate on primary biliary cholangitis with ...

Conclusions: Administration of PEM is effective in PBC patients with dyslipidemia who are refractory to UDCA monotherapy. In patients using both UDCA and BEZ, ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06247735

NCT06247735 | Study to Evaluate the Efficacy and Safety ...

Study to Evaluate the Efficacy and Safety of K-808 (Pemafibrate) in Participants With Primary Biliary Cholangitis (PBC) With Inadequate Response to ...

3.

onlinelibrary.wiley.com

onlinelibrary.wiley.com/doi/abs/10.1111/hepr.14172

Pemafibrate improves liver biochemistry and GLOBE ...

Pemafibrate add-on or switch therapy improved liver biochemistry and GLOBE scores. Pemafibrate may be useful as a second-line drug when UDCA alone is ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11980239/

Efficacy and safety of PPAR agonists in primary biliary ...

The current study demonstrates that combining UDCA and PPAR agonists effectively reduces ALP, GGT, and Bilirubin levels, crucial markers for effective therapy ...

5.

clinicaltrials.cedars-sinai.edu

clinicaltrials.cedars-sinai.edu/view/K-808-2-01

K-808 (Pemafibrate) in Primary Biliary Cholangitis

The purpose of this study is to determine the safety and effectiveness of an experimental drug called K-808 in participants with primary biliary cholangitis ( ...

6.

sciencedirect.com

sciencedirect.com/science/article/pii/S0140673624013035

Primary biliary cholangitis

Open-label, clinical trial extension: two-year safety and efficacy results of seladelpar in patients with primary biliary cholangitis.