Primary Sclerosing Cholangitis
Conditions
Brief summary
A Phase 2a, multicenter, randomized, double-blind, dose-ranging, placebo-controlled, study to evaluate the safety, tolerability, and PK of PLN-74809 in participants with primary sclerosing cholangitis and suspected liver fibrosis
Detailed description
Three-part study: Part 1 - 12-week treatment period evaluating 40 mg of PLN-74809 or matching placebo \[Complete\] Part 2 - 12-week treatment period evaluating two dose groups, 80 mg and 160 mg of PLN-74809 or matching placebo Part 3 - minimum 24-week, up to 48-week treatment period evaluating 320 mg of PLN-74809 or matching placebo
Interventions
DRUGPLN-74809
PLN-74809
DRUGPlacebo
Placebo
Sponsors
Pliant Therapeutics, 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 75 Years
Healthy volunteers
No
Inclusion criteria
* Established clinical diagnosis of large duct PSC based on an abnormal cholangiography as assessed by magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP), and/or percutaneous transhepatic cholangiopancreatography (PTC) in the context of cholestatic liver chemistry * Suspected liver fibrosis, as defined by liver stiffness measurement (LSM), assessed by ultrasound-based transient elastography (TE, FibroScan®) OR Enhanced Liver Fibrosis (ELF) Score OR Historical liver biopsy showing fibrosis without cirrhosis (by any scoring system) OR Magnetic resonance elastography (MRE) * Serum ALP concentration within normal limits or \> 1 times the upper limit of normal (ULN) * Participants receiving treatment for IBD are allowed, if on a stable dose from screening and expected to remain stable for the duration of the study * Serum AST and ALT concentration ≤ 5 times the upper limit of normal * If receiving treatment with UDCA, therapy is at a dose of \< 25 mg/kg/day, has been stable for at least 3 months before screening.
Exclusion criteria
* Other causes of liver disease, including secondary sclerosing cholangitis or viral, metabolic, or alcoholic liver disease, as assessed clinically * Known or suspected overlapping clinical and histologic diagnosis of autoimmune hepatitis * Small duct PSC with no evidence of large duct involvement (evidence of PSC on historical liver histology, with normal bile ducts on cholangiography) * Presence of liver cirrhosis as assessed by liver histology, ultrasound-based liver stiffness measurement, ELF score, MRE, and/or signs and symptoms of hepatic decompensation (including but not limited to, jaundice, ascites, variceal hemorrhage, and/or hepatic encephalopathy. * Serum ALP concentration \> 10 times the upper limit of normal.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events | Up to 40 weeks | Nature and proportion of TEAEs between PLN-74809 and placebo groups. Treatment-emergent adverse events (TEAEs) are defined as AEs that emerged or worsened in severity after the first administration of study drug |
| Number of Participants With Serious Treatment Emergent Adverse Events | Up to 40 weeks | Nature and proportion of Serious TEAEs between PLN-74809 and placebo groups. An SAE was defined as an event that, at any dose, results in the following: death, a life-threatening situation; in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect or a medically important event or reaction. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of PLN-74809 Total Plasma Concentrations at Week 12 | Up to 12 weeks | Assessment of PLN-74809 Total Plasma Concentrations Week 12, 2 Hour Post Dose |
| Assessment of PLN-74809 Total Plasma Concentrations at Week 24 | Up to 24 weeks | Assessment of PLN-74809 Total Plasma Concentrations Week 24, 2 Hour Post Dose |
Countries
Australia, Austria, Belgium, Canada, France, Germany, Netherlands, United Kingdom, United States
Contacts
STUDY_DIRECTORPliant Therapeutics Medical Monitor
Pliant Therapeutics, Inc.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 47.1 years STANDARD_DEVIATION 14.47 |
| BMI at Screening | 26.52 kg/m^2 STANDARD_DEVIATION 4.566 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 110 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 20 Participants |
| Region of Enrollment Australia | 2 participants |
| Region of Enrollment Austria | 1 participants |
| Region of Enrollment Belgium | 0 participants |
| Region of Enrollment Canada | 5 participants |
| Region of Enrollment France | 1 participants |
| Region of Enrollment Germany | 0 participants |
| Region of Enrollment Netherlands | 2 participants |
| Region of Enrollment United Kingdom | 10 participants |
| Region of Enrollment United States | 43 participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 24 | 0 / 20 | 0 / 20 | 0 / 27 |
| other Total, other adverse events | 21 / 30 | 10 / 24 | 16 / 20 | 15 / 20 | 23 / 27 |
| serious Total, serious adverse events | 1 / 30 | 1 / 24 | 1 / 20 | 0 / 20 | 1 / 27 |
Outcome results
None listed