A POC and Dose-Ranging Study of HTD1801 in PSC Patients

HighTide Therapeutics

Status and phase: Completed; Phase 2

Conditions: Primary Sclerosing Cholangitis (PSC)

Treatments: Drug: Placebo; Drug: HTD1801

Study type: Interventional

Funder types: Industry

Identifiers

NCT03333928

HTD1801.PCT003

Details and patient eligibility

About

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.

Enrollment: 59 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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;

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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59 participants in 3 patient groups, including a placebo group

HTD1801 500 mg BID

Active Comparator group

Treatment:

Drug: HTD1801

HTD1801 1000 mg BID

Active Comparator group

Treatment:

Drug: HTD1801

Placebo BID

Placebo Comparator group

Treatment:

Drug: Placebo