Vidofludimus Calcium for Primary Sclerosing Cholangitis
Condition: Primary Sclerosing Cholangitis
MeSH terms: Cholangitis; Cholangitis, Sclerosing
Intervention: Vidofludimus calcium
Intervention description: During the 6-month treatment period, subjects will receive 30 mg VC orally once daily. This will be preceded by a lead-in dosing period where subjects will receive 15 mg VC once daily for 1 week.
Intervention MeSH terms: Calcium
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      To examine the safety, tolerability, and efficacy of daily dosing with vidofludimus calcium
      over a 6-month period.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female subject age 18-75 years

          2. Diagnosis of PSC consistent with the guidelines published by the AASLD. All subjects
             must have an elevated serum ALP of at least 1.5 times upper limit of normal (ULN) at
             baseline plus cholangiographic evidence of PSC (MRI, endoscopic retrograde
             cholangiography, or direct cholangiography).

          3. Indirect bilirubin <1.2 times the ULN

          4. An ultrasound (or equivalent imaging modality) that excludes biliary obstruction and
             malignancy within 6 months of study enrollment

          5. PSC with or without inflammatory bowel disease, such as ulcerative colitis or Crohn's
             disease

          6. Must agree to comply with the study protocol and provide informed consent

        Exclusion Criteria:

          1. Pregnancy, attempting to become pregnant, or breastfeeding

          2. Active hepatitis A or B infection

          3. Active hepatitis C infection (antibody positive); patients with a history of hepatitis
             C infection will be eligible for this study if they have undetectable levels of HCV
             RNA

          4. HIV/AIDS (per medical record or HIVAb/HIA antigen), tuberculosis, or positive
             interferon-gamma assay (IGRAs) for Mycobacterium tuberculosis

          5. Other cholestatic liver disease such as primary biliary cholangitis and cholestatic
             diseases of pregnancy

          6. Metabolic liver diseases such as Wilson's disease, Gilbert's syndrome or
             hemochromatosis

          7. Serum uric acid levels at screening >1.2 ULN

          8. Inherited diseases of the liver such as α-1 antitrypsin deficiency

          9. Immunoglobulin G4-related cholangitis

         10. PSC with concomitant autoimmune hepatitis (AIH) and/or primary biliary cholangitis

         11. Secondary sclerosing cholangitis (SSC)

         12. Active acute ascending cholangitis requiring antibiotics

         13. CCA (malignant biliary stricture, neoplasm, and cytology/histopathology or positive
             fluorescence in situ hybridization (FISH) consistent with adenocarcinoma of the bile
             duct)

         14. A liver biopsy, if one has been previously obtained, which showed non-alcoholic
             steatohepatitis (NASH). Patients with suspected fatty liver by imaging will not be
             excluded.

         15. Presence of complications of advanced PSC such as hepatic encephalopathy, portal
             hypertension, hepato-renal syndrome, and hepato-pulmonary syndrome

         16. History of liver transplantation, anticipated need for liver transplantation within 12
             months from randomization, a Model of End-stage Liver Disease (MELD) score of ≥15, or
             a Child Pugh score >6

         17. Ongoing alcohol abuse (>4 drinks per day for men, and >2 drinks per day for women)

         18. Moderate-to-severe renal impairment with a calculated creatinine clearance of
             <60mL/min

         19. Any other conditions or abnormalities that, in the opinion of the investigator, may
             compromise the safety of the subject or interfere with the subject participating in or
             completing the study

         20. Evidence of, or treatment for, C. difficile infection within 30 days before the
             initiation of the study drug

         21. Evidence of active C. difficile infection during the screening phase confirmed by a
             positive C. difficile toxin B

         22. Subjects who have been treated for intestinal pathogens other than C. difficile
             infection within 30 days prior to study drug initiation

         23. Received or plan to receive live vaccine within 30 days prior to, and through the end
             of the study

         24. Use of methotrexate at dose ≥17.5mg/week

         25. Rosuvastatin exceeding 10 mg daily