A POC and Dose-Ranging Study of HTD1801 in PSC Patients
Condition: Primary Sclerosing Cholangitis (PSC)
MeSH terms: Cholangitis; Cholangitis, Sclerosing
Intervention: HTD1801; Placebo
Intervention description: HTD1801 tablets, 250 mg; tablets manufactured to mimic HTD1801 tablets
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: A primary parallel group comparison for a 6-week treatment period (Period 1), followed by a 6-week dose-controlled extension (Period 2), and followed by a 6-week placebo-controlled randomized withdrawal (Period 3).
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 59.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      The study was a dose-ranging, 18-week study comparing two doses of HTD1801 (500 mg BID and
      1000 mg BID) to placebo in adult subjects with PSC.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female between 18 and 75 years of age;

          -  Have a clinical diagnosis of PSC as evident by chronic cholestasis of more than six
             months duration with either a consistent magnetic resonance cholangiopancreatography
             (MRCP)/endoscopic retrograde cholangiopancreatography (ERCP) showing sclerosing
             cholangitis;

          -  If subjects have Inflammatory Bowel Disease (IBD) they will be eligible to
             participate. If a subject has IBD, documented evidence of IBD must have been evident
             by prior endoscopy or in previous medical records for ≥6 months. In addition, subjects
             may only enter the study with a Partial Mayo Score of 0-4, inclusively. Subjects who
             are on treatment are allowed, provided they are stable for 3 months if taking:

               1. 5-amino salicylic acid drugs,

               2. azathioprine,

               3. 6-mercaptopurine, or methotrexate

               4. biologics;

          -  Have a serum ALP ≥1.5 × upper limit of normal (ULN);

          -  Be able to understand and sign a written informed consent form (ICF);

          -  Subjects receiving allowed concomitant medications need to be on stable therapy for 28
             days prior to the Baseline visit, with the exception of ursodeoxycholic acid (UDCA),
             which should be stable for at least 6 weeks prior to the Baseline visit.

        Exclusion Criteria:

          -  Presence of documented secondary sclerosing cholangitis (such as ischemic cholangitis,
             recurrent pancreatitis, intraductal stone disease, severe bacterial cholangitis,
             surgical or blunt abdominal trauma, recurrent pyogenic cholangitis,
             choledocholithiasis, toxic sclerosing cholangitis due to chemical agents, or any other
             cause of secondary sclerosing cholangitis) on prior clinical investigations;

          -  Small duct PSC;

          -  Presence of percutaneous drain or bile duct stent;

          -  History of cholangiocarcinoma or clinical suspicion of new dominant stricture within 1
             year by MRCP/ERCP. Presence of dominant stricture without ERCP evidence of
             cholangiocarcinoma is acceptable if stable for ≥ 1 year;

          -  Ascending cholangitis within 60 days prior to Screening;

          -  History of alcohol or substance abuse or dependence;

          -  Prior or planned liver transplantation;

          -  Presence of alternative causes of chronic liver disease, including alcoholic liver
             disease, nonalcoholic steatohepatitis, primary biliary cirrhosis, autoimmune
             hepatitis;

          -  Platelet count below 125,000/mm3, albumin below 3.0 g/dL, International Normalized
             Ratio (INR) > 1.2, or a history of ascites, or encephalopathy, or history of
             esophageal variceal bleeding;

          -  Severe active IBD or flare in colitis activity within the last 90 days requiring
             intensification of therapy beyond baseline treatment;