Pemafibrate for Primary Biliary Cirrhosis

Recruiting at 37 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

45 Participants Needed

Trial Summary

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.

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}

What is the purpose of this trial?

Study to investigate the efficacy and safety of two doses of K-808 (pemafribate) in subjects with PBC.

Research Team

Andre Belous, MD, PhD

Principal Investigator

Kowa Pharma Development Co.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

References

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

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

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

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

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

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

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

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

5. 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]