Study to Evaluate the Efficacy and Safety of K-808 (Pemafibrate) in Participants With Primary Biliary Cholangitis (PBC) With Inadequate Response to Ursodeoxycholic Acid (UDCA) and/or Obeticholic Acid (OCA) Treatment.

A Phase 2, Randomized, Placebo-controlled, Parallel Group, Multicenter 12-week Study With a 52-week Extension to Evaluate the Efficacy and Safety of Two Doses of K-808 (Pemafibrate) in Subjects With Primary Biliary Cholangitis With Inadequate Response to Ursodeoxycholic Acid and/or Obeticholic Acid Treatment

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

Study Overview

• Status: Recruiting
• Conditions: Primary Biliary Cholangitis
• Intervention / Treatment: Drug: Placebo; Drug: K-808 (Dose A); Drug: K-808 (Dose B)

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Director, Clinical Operations; Phone Number: 919-433-1600; Email: Clinical@KowaUS.com

Study Locations

• Japan
  • Sapporo, Japan
    • Not yet recruiting
    • Teine Keijinkai Hospital
• United States
  • Illinois
    • Springfield, Illinois, United States, 62702
      • Recruiting
      • Springfield Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female participant who has a PBC diagnosis as 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

• Participant has the following qualifying biochemistry value at Screening:

  • ALP ≥1.5 × ULN
• Participant is ≥18 years of age at consent.
• Participant meets all other eligibility criteria outlined in the Clinical Study Protocol.

Exclusion Criteria:

• Participant meets any one of the following criteria at Screening:

  • ALP>10 × ULN
  • ALT or AST >5 × ULN
  • Hepatitis C treatment within 5 years of Screening, or active hepatitis C as defined by positive hepatitis C antibody with the presence of hepatitis C virus ribonucleic acid; subjects with active hepatitis B (HBV) infection (hepatitis B surface antigen [HbsAg] positive) will be excluded. A subject with resolved hepatitis A at least 3 months prior to the Screening Visit can be screened.
  • Primary sclerosing cholangitis and secondary sclerosing cholangitis (eg, due to cholangiolithiasis, ischemia, telangiectasia, vasculitis, infectious diseases)
  • Alcoholic liver disease
  • History of definite autoimmune hepatitis or PBC/autoimmune hepatitis overlap, defined as both of the following: 1) IgG >2 × ULN and/or positive anti-smooth muscle antibodies, 2) liver histology revealing moderate or severe periportal or periseptal inflammation
  • Nonalcoholic steatohepatitis (NASH)
  • Gilbert's Syndrome
  • Alpha-1-antitrypsin deficiency, cystic fibrosis, Wilson's disease, hemochromatosis based on historically established diagnosis
  • Drug-induced liver injury (DILI) as defined by typical exposure and history
  • Known condition that involves bile duct obstruction or cholestasis other than PBC, eg, vascular diseases (eg, Budd-Chiari syndrome, sinusoidal obstruction syndrome, congestive hepatopathy), congenital conditions (ductal plate malformations, Caroli syndrome, congenital liver fibrosis), idiopathic ductopenia
  • Hepatocellular carcinoma
• Participant meets any other exclusion criteria outlined in the Clinical Study Protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo + K-877 (Group A); Placebo for 12 Weeks followed by K-808 (Dose A) for 52 Weeks	Drug: Placebo; Administered orally once daily; Drug: K-808 (Dose A); Administered orally once daily; Other Names: Pemafibrate
Placebo Comparator: Placebo + K-877 (Group B); Placebo for 12 Weeks followed by K-808 (Dose B) for 52 Weeks	Drug: Placebo; Administered orally once daily; Drug: K-808 (Dose B); Administered orally once daily; Other Names: Pemafibrate
Experimental: K-808 Group A; K-808 (Dose A) for 64 Weeks	Drug: K-808 (Dose A); Administered orally once daily; Other Names: Pemafibrate
Experimental: K-808 Group B; K-808 (Dose B) for 64 Weeks	Drug: K-808 (Dose B); Administered orally once daily; Other Names: Pemafibrate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent change from baseline in serum alkaline phosphatase (ALP)	Two doses of K-808 compared to placebo after 12 weeks of treatment	Baseline to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Achievement of normalization of ALP level	ALP ≤1 × upper limit of normal (ULN)	Baseline to Week 12
Achievement of target levels of ALP and total bilirubin (TB)	After two doses of K-808	Baseline to Weeks 12 and 64
Change from baseline in liver function parameters	liver function test results including ALP, total and conjugated bilirubin, albumin, international normalized ratio [INR], γ-GT, ALT, AST, albumin, platelets count	Baseline to Weeks 12 and 64
Change from baseline in GLOBE risk score	calculated by GLOBE scoring system which is calculated based on serum values of bilirubin, ALP, albumin and platelet count.	Baseline to Weeks 12 and 64
Change from baseline in UK-PBC score	PBC risk score developed by United Kingdom (UK)-PBC Consortium is a scoring system and the calculation is based on laboratory test measurements and upper limits of normal (ULN) for the total bilirubin (BIL12); alanine transaminase or aspartate transaminase (TA12), and alkaline phosphatase (ALP12) after at least 12 months of UDCA, and the laboratory test measurements and lower limits of normal (LLN) for the serum albumin and platelet count in the same timeframe. A high number is indicative of a worse score.	Baseline to Weeks 12 and 64
Incidence of Treatment Emergent Adverse Events (TEAEs)	Coded using the most recent version of Medical Dictionary of Regulatory Activities (MedDRA).	Baseline to Week 68

Collaborators and Investigators

• Sponsor: Kowa Research Institute, Inc.
• Investigators: Study Chair: Shona Pendse, MD, MMSc, Kowa Pharma Development Co.

Study record dates

Study Major Dates

• Study Start (Actual): January 26, 2024
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): April 8, 2026

Study Registration Dates

• First Submitted: January 22, 2024
• First Submitted That Met QC Criteria: January 30, 2024
• First Posted (Actual): February 8, 2024

Study Record Updates

• Last Update Posted (Actual): February 8, 2024
• Last Update Submitted That Met QC Criteria: January 30, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Biliary Tract Diseases; Bile Duct Diseases; Cholestasis, Intrahepatic; Cholestasis; Liver Cirrhosis; Cholangitis; Liver Cirrhosis, Biliary
• Other Study ID Numbers: K-808-2.01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No