A POC and Dose-Ranging Study of HTD1801 in PSC Patients
- Conditions
- Primary Sclerosing Cholangitis (PSC)
- Interventions
- Drug: Placebo
- Registration Number
- NCT03333928
- Lead Sponsor
- HighTide Biopharma Pty Ltd
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 59
-
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:
- 5-amino salicylic acid drugs,
- azathioprine,
- 6-mercaptopurine, or methotrexate
- 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.
- 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;
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo BID Placebo - HTD1801 500 mg BID HTD1801 - HTD1801 1000 mg BID HTD1801 -
- Primary Outcome Measures
Name Time Method Absolute Change in Serum Alkaline Phosphatase (ALP) From Baseline to Week 6 in Period 1 Baseline to Week 6
- Secondary Outcome Measures
Name Time Method Percentage of Subjects Who Achieve ALP of <1.5 x ULN at the End of Week 6 (Period 1) Baseline to Week 6 Percentage of Patients Who Normalize ALP at the End of Week 12 (Period 2) Week 6 to Week 12 Percentage of Subjects Who Normalize ALP at the End of Week 6 (Period 1) Baseline to Week 6 Percentage of Subjects Who Achieve ALP of <1.5 x ULN at the End of Week 12 (Period 2) Week 6 to Week 12 Percentage of Subjects Who Normalize ALP at the End of Week 18 (Period 3) Week 12 to Week 18 Percentage of Subjects Who Achieve a 50% Decrease in ALP at the End of Week 6 (Period 1) Baseline to Week 6 Absolute Change in Serum ALP From Week 6 to Week 12 (Period 2) Week 6 to Week 12 Percentage of Patients Who Achieve a 50% Decrease in ALP at the End of Week 12 (Period 2) Week 6 to Week 12 Percentage of Patients Who Achieve ALP of <1.5 x ULN at the End of Week 18 (Period 3) Week 12 to Week 18 The percentage of patients who achieve ALP of \<1.5 x ULN at the end of week 18 (Period 3)
Absolute Change in Serum ALP From Week 12 to Week 18 (Period 3) Week 12 to Week 18 Change in serum ALP between a new baseline at Week 12 and the final value at Week 18 for all subjects following the randomized withdrawal
Absolute Change in Serum Total Bilirubin at the End of Week 18 (Period 3) Week 12 to Week 18 Absolute Change in Serum Total Bilirubin at the End of Week 6 (Period 1) Baseline to Week 6 Absolute Change in Serum Total Bilirubin at the End of Week 12 (Period 2) Week 6 to Week 12 Percentage of Patients Who Achieve a 50% Decrease in ALP at the End of Week 18 (Period 3) Week 12 to Week 18
Trial Locations
- Locations (24)
Toronto Centre for Liver Disease, Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
Mercy Medical Center
🇺🇸Baltimore, Maryland, United States
University of Miami
🇺🇸Miami, Florida, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Pinnacle Clinical Research
🇺🇸San Antonio, Texas, United States
University of Washington
🇺🇸Seattle, Washington, United States
Arizona Liver Health
🇺🇸Tucson, Arizona, United States
Keck School of Medicine of USC
🇺🇸Los Angeles, California, United States
Fresno Clinical Research Center
🇺🇸Fresno, California, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
South Denver Gastroenterology, PC
🇺🇸Englewood, Colorado, United States
Florida Research Institute
🇺🇸Lakewood Ranch, Florida, United States
Michigan Medicine University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Gastrointestinal Associates
🇺🇸Flowood, Mississippi, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Mount Sinai - Icahn School of Medicine
🇺🇸New York, New York, United States
Cumberland Research Associates
🇺🇸Fayetteville, North Carolina, United States
Wake Forest Baptist Health
🇺🇸Winston-Salem, North Carolina, United States
Gastro One
🇺🇸Germantown, Tennessee, United States
Swedish Medical Center
🇺🇸Seattle, Washington, United States
Aspen Woods Clinic
🇨🇦Calgary, Alberta, Canada
University of Colorado, Denver
🇺🇸Aurora, Colorado, United States
Walter Reed National Military Medical Center
🇺🇸Bethesda, Maryland, United States
Yale School of Medicine
🇺🇸New Haven, Connecticut, United States