Global Prospective, Observational Cohort of Adult Patients With Primary Sclerosing Cholangitis (WIND-PSC Study)

Official title

A Global Multi-Center Prospective Observational Cohort to Support Drug Development in Adult Patients With Primary Sclerosing Cholangitis (WIND-PSC)

Overview

Develop an appropriate real-world data comparator cohort to support the design, execution, and serve as an external control for interventional clinical trials in PSC.

Detailed description

Global, multi-center longitudinal observational cohort study. Collection of prospective clinical data to include liver-related clinical outcomes and safety events, hepatobiliary malignancies, relevant key biomarkers, imaging assessments, PSC-related clinical symptoms, patient-reported outcomes, and medication use in adult patients with PSC.

Primary outcome measures

• Develop an appropriate real-world data (RWD) comparator cohort to support the design, execution, and serve as an external control for interventional clinical trials in PSC. [Time frame: Quarterly for five years from enrollment]

Secondary outcome measures (3)

• Develop a large clinical and biomarker data set to identify individual and/or composite surrogate end-points likely to predict clinical benefit for use in the design of interventional studies in PSC. [Time frame: Quarterly for five years from enrollment]
• Develop a large clinical and biomarker data set to identify individual and/or composite surrogate end-points likely to predict clinical benefit for use in the design of interventional studies in PSC. [Time frame: Quarterly for five years from enrollment]
• Evaluate direct participant experiences with standardized tools to determine changes over time, the association with clinical events, biomarkers, and disease progression [Time frame: Quarterly for five years from enrollment]

Eligibility criteria

Inclusion criteria

• Adult patients between 18 and 75 years of age (inclusive) who can comprehend instructions, follow the study procedures and are willing to sign an Informed Consent Form (ICF).
• Confirmed clinical diagnosis of large duct PSC.

Exclusion criteria

• Clinically significant acute or chronic liver disease of an etiology other than PSC (including but not limited to metabolic-dysfunction associated steatohepatitis (MASH), PBC, HCV, HBV, or alcoholic hepatitis, Wilson's disease, alpha-1 antitryp-sin deficiency, acute or chronic drug-induced liver injury)

• Patients with PSC and elements of AIH overlap are allowed to enroll
• Patients with metabolic dysfunction associated steatotic liver disease (MASLD) or benign steatosis are allowed to enroll
• Small-Duct PSC.
• Clinically diagnosed secondary or IgG4-related sclerosing cholangitis.
• Clinically diagnosed infections (including acute cholangitis) and receiving treatment within the past 7 days; patients on chronic suppressive antibiotics for acute cholangitis will be allowed to enroll
• Hospitalization in the past 7 days
• UDCA dose >28 mg/kg
• Evidence of current or historical decompensated cirrhosis based on the following clinical events:

• Ascites > Grade 2 and requiring treatment
• Esophageal or gastric variceal bleeding requiring hospitalization
• Hepatic encephalopathy (as defined by a West Haven score ≥ 2)
• Spontaneous bacterial peritonitis defined as ascites absolute neutrophil count >250/mm3 in the absence of an intra-abdominal source of infection
• AKI-HRS according to AASLD Guidelines (Flamm 2021)
• Portal hypertension based on a platelet count < 150 × 109/L and LSM > 15 kPa with clinical, laboratory, imaging and/or other relevant parameters
• Prior liver transplantation
• MELD 3.0 Score >15. For subjects on anticoagulation medication, baseline INR determination for MELD score calculation should take this use into account.
• History, evidence, or high suspicion of hepatobiliary malignancies or active colon cancer based on imaging, screening laboratory values, and/or clinical symptoms. Patients with a history of colon cancer who have undergone a colectomy and have no current evidence of colon cancer will be allowed to enroll in the study.
• Participants with current clinical or laboratory evidence of any severe, progressive, or uncontrolled disease, related or unrelated to PSC and which, in the opinion of the investigator, has an expected survival of less than 52 weeks.
• Participants who are impaired, incapacitated, or incapable of completing study-related assessments or giving informed consent.
• Prisoners or participants who are involuntarily incarcerated.
• Participants who are currently participating in an investigational PSC therapy clinical study or who have participated in such a study within the past 12 weeks
• Absence of data in medical records to assess inclusion and exclusion criteria.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

United States · 11 centers

• UC Davis — Sacramento
• California Pacific Medical Center — San Francisco
• University of California, San Francisco — San Francisco
• Yale University — New Haven
• Schiff Center for Liver Diseases / University of Miami — Miami
• Indiana University — Indianapolis
• Massachusetts General Hospital — Boston
• Beth Israel Deaconess Medical Center — Boston
• … and 3 more centers

Canada · 3 centers

• University of Alberta — Edmonton
• University Health Network — Toronto
• Centre de recherche du centre hospitalier de l'Université de Montréal (CRCHUM) — Montreal

Germany · 1 center

• University Medical Center Hamburg-Eppendorf — Hamburg

Italy · 1 center

• University of Milano Bicocca — Milan

New Zealand · 1 center

• Auckland University — Auckland

United Kingdom · 1 center

• Oxford University Hospitals — Oxford

Identifiers

NCT: NCT06297993 · WIND-PSC-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗