Pemafibrate for Primary Biliary Cirrhosis

No longer recruiting at 13 trial locations

Overseen By Director, Clinical Operations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Kowa Research Institute, Inc.

Disqualifiers: Pregnancy, Breastfeeding, Drug absorption issues, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called Pemafibrate for individuals with Primary Biliary Cholangitis (PBC). The goal is to understand the drug's behavior in the body and assess its safety. Participants will have PBC either with or without cirrhosis (liver damage). It suits those with PBC, as indicated by specific liver test results or antibodies in the blood, and who do not have severe digestive issues. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the study team for guidance.

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

Research has shown that pemafibrate is generally safe and well-tolerated. Studies involving over 3,000 patients with high cholesterol indicate its safety. Pemafibrate helps improve triglycerides (a type of fat in the blood) and liver health markers. However, it is not recommended for individuals with severe kidney problems, as the liver primarily processes it. Overall, evidence suggests that pemafibrate is safe for most people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for PBC?

Pemafibrate is unique because it targets a different pathway compared to current treatments for Primary Biliary Cirrhosis (PBC), such as ursodeoxycholic acid (UDCA) and obeticholic acid. While most existing options work by improving bile flow or reducing liver inflammation, pemafibrate acts on the PPAR-alpha receptor, which may help reduce liver damage and improve lipid metabolism. Researchers are excited about pemafibrate’s potential to offer a new mechanism of action that could provide better management of symptoms and slow disease progression for patients with PBC.

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

Research has shown that pemafibrate might help people with primary biliary cholangitis (PBC). In earlier studies, pemafibrate improved liver health by lowering levels of ALP and GGT, important indicators of liver function. It also proved effective for patients who did not respond to the usual treatment, UDCA. This trial will evaluate pemafibrate in different treatment arms, including those with and without cirrhosis. Overall, early evidence suggests pemafibrate could be a promising choice for those with PBC, especially when other treatments aren't enough. ^{4 6 7 8 9}

Who Is on the Research Team?

Sara Neville, MD

Principal Investigator

Kowa Research Institute, Inc.

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Primary Biliary Cholangitis (PBC), either with well-compensated cirrhosis or without. Participants must have a history of liver enzyme levels above normal and positive antibodies related to PBC. They should understand the study procedures and agree to follow them.

Inclusion Criteria

Able to understand and comply with study requirements and procedures and provide written informed consent

Meet all other inclusion criteria outlined in the clinical study protocol

I have PBC with well-compensated cirrhosis (Child-Pugh A).

Exclusion Criteria

I am not pregnant, breastfeeding, nor planning to become pregnant during the study.

I have conditions that could affect how my body absorbs medication.

I haven't been in a drug study within the last 8 weeks or an antibody study in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of K-808 followed by an optional multiple-dose treatment period

8 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 trial is testing K-808, also known as Pemafibrate, in patients with PBC. It aims to understand how the drug moves through and affects the body (pharmacokinetics) and its safety profile in those with compensated cirrhosis compared to those without.

How Is the Trial Designed?

Group I: PBC w/o CIRR Experimental Treatment 1 Intervention

K-808 single dose followed by multiple-dose treatment period.

Group II: PBC w/ CIRR CP-A Experimental Treatment 1 Intervention

K-808 single dose followed by optional multiple-dose treatment period.

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 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]

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]

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. bmcgastroenterol.biomedcentral.com bmcgastroenterol.biomedcentral.com/articles/10.1186/s12876-025-03821-2

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11802250/

Pharmacokinetics and Safety of Pemafibrate in Patients ... Aims: Per the package insert, pemafibrate was contraindicated for use in patients with severe renal impairment despite its biliary excretion.

7. hsa.gov.sg hsa.gov.sg/docs/default-source/hprg-tpb/summary-reports/parmodia-summary-report.pdf?sfvrsn=55dc6039_0

parmodia-summary-report.pdf ... pemafibrate 0.4 mg/day. D ASSESSMENT OF CLINICAL SAFETY. The clinical safety of Parmodia was based on safety data in 3,079 patients with dyslipidaemia pooled ...

8. pharmaceutical-technology.com pharmaceutical-technology.com/data-insights/pemafibrate-kowa-primary-biliary-cholangitis-primary-biliary-cirrhosis-likelihood-of-approval/

Pemafibrate by Kowa for Primary Biliary Cholangitis ... Pemafibrate is under clinical development by Kowa and currently in Phase II for Primary Biliary Cholangitis (Primary Biliary Cirrhosis).

9. sciencedirect.com sciencedirect.com/science/article/pii/S2772487524001247

Evaluation of the beneficial effects of pemafibrate in ... Pemafibrate improves TG, HDL-C, hepatic biomarkers and hypertriglyceridemia regardless of alcohol consumption and is safe.