Primary Biliary Cholangitis
Conditions
Brief summary
Study to investigate the efficacy and safety of two doses of K-808 (pemafribate) in subjects with PBC.
Interventions
DRUGK-808 (Dose A)
Administered orally once daily
DRUGK-808 (Dose B)
Administered orally once daily
DRUGPlacebo
Administered orally once daily
Sponsors
Kowa Research Institute, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent change from baseline in serum alkaline phosphatase (ALP) | Baseline to Week 12 | Two doses of K-808 compared to placebo after 12 weeks of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Achievement of normalization of ALP level | Baseline to Week 12 | ALP ≤1 × upper limit of normal (ULN) |
| Achievement of target levels of ALP and total bilirubin (TB) | Baseline to Weeks 12 and 64 | After two doses of K-808 |
| Change from baseline in liver function parameters | Baseline to Weeks 12 and 64 | liver function test results including ALP, total and conjugated bilirubin, albumin, international normalized ratio \[INR\], γ-GT, ALT, AST, albumin, platelets count |
| Change from baseline in GLOBE risk score | Baseline to Weeks 12 and 64 | calculated by GLOBE scoring system which is calculated based on serum values of bilirubin, ALP, albumin and platelet count. |
| Change from baseline in UK-PBC score | Baseline to Weeks 12 and 64 | 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. |
| Incidence of Treatment Emergent Adverse Events (TEAEs) | Baseline to Week 68 | Coded using the most recent version of Medical Dictionary of Regulatory Activities (MedDRA). |
Countries
Canada, Japan, United States
Contacts
STUDY_DIRECTORAndre Belous, MD, PhD
Kowa Pharma Development Co.
Outcome results
None listed