Pemafibrate for Primary Biliary Cirrhosis

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

17 Participants Needed

Trial Summary

What is the purpose of this trial?

A Trial to Investigate the Pharmacokinetics (PK) Effects and Safety Profile of K-808 (Pemafibrate) in Primary Biliary Cholangitis (PBC) Subjects with and without Cirrhosis.

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.

How is the drug pemafibrate different from other treatments for primary biliary cirrhosis?

Pemafibrate is unique because it is specifically studied for its effects on primary biliary cholangitis (a condition similar to primary biliary cirrhosis) in patients with dyslipidemia (abnormal cholesterol levels), which may offer benefits beyond standard treatments like ursodeoxycholic acid. ^{1 2 3 4 5}

Research Team

Sara Neville, MD

Principal Investigator

Kowa Research Institute, Inc.

Eligibility Criteria

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

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

I am 18 years old or older.

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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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]

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]

References

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

Bezafibrate normalizes alkaline phosphatase in primary biliary cirrhosis patients with incomplete response to ursodeoxycholic acid. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of pemafibrate on primary biliary cholangitis with dyslipidemia. [2022]

3. Japan pubmed.ncbi.nlm.nih.gov

Bezafibrate treatment: a new medical approach for PBC patients? [2022]

4. Japan pubmed.ncbi.nlm.nih.gov

Biochemical responses to bezafibrate improve long-term outcome in asymptomatic patients with primary biliary cirrhosis refractory to UDCA. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Seladelpar: an investigational drug for the treatment of early-stage primary biliary cholangitis (PBC). [2023]