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

Primary Sclerosing Cholangitis (PSC) Clinical Trial

Official title:

A Proof-of-Concept and Dose-Ranging Study Investigating the Efficacy and Safety of HTD1801 in Adult Subjects With Primary Sclerosing Cholangitis (PSC)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03333928
• Other study ID #: HTD1801.PCT003
• Status: Completed
• Phase: Phase 2
• Start date: February 9, 2018
• Est. completion date: August 14, 2020

Study information

• Verified date: March 2022
• Source: HighTide Biopharma Pty Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: August 14, 2020
• Est. primary completion date: April 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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;

Related Conditions & MeSH terms

• Cholangitis
• Cholangitis, Sclerosing
• Primary Sclerosing Cholangitis (PSC)

Intervention

Drug:
• HTD1801
HTD1801 tablets, 250 mg
• Placebo
tablets manufactured to mimic HTD1801 tablets

Locations

Country	Name	City	State
Canada	Aspen Woods Clinic	Calgary	Alberta
Canada	Toronto Centre for Liver Disease, Toronto General Hospital	Toronto	Ontario
United States	Michigan Medicine University of Michigan	Ann Arbor	Michigan
United States	University of Colorado, Denver	Aurora	Colorado
United States	Pinnacle Clinical Research	Austin	Texas
United States	Mercy Medical Center	Baltimore	Maryland
United States	Walter Reed National Military Medical Center	Bethesda	Maryland
United States	Arizona Liver Health	Chandler	Arizona
United States	South Denver Gastroenterology, PC	Englewood	Colorado
United States	Cumberland Research Associates	Fayetteville	North Carolina
United States	Gastrointestinal Associates	Flowood	Mississippi
United States	Fresno Clinical Research Center	Fresno	California
United States	Gastro One	Germantown	Tennessee
United States	Florida Research Institute	Lakewood Ranch	Florida
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Keck School of Medicine of USC	Los Angeles	California
United States	University of Miami	Miami	Florida
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Yale School of Medicine	New Haven	Connecticut
United States	Mount Sinai - Icahn School of Medicine	New York	New York
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Pinnacle Clinical Research	San Antonio	Texas
United States	Swedish Medical Center	Seattle	Washington
United States	University of Washington	Seattle	Washington
United States	Arizona Liver Health	Tucson	Arizona
United States	Wake Forest Baptist Health	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
HighTide Biopharma Pty Ltd

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Absolute Change in Serum Alkaline Phosphatase (ALP) From Baseline to Week 6 in Period 1		Baseline to Week 6
Secondary	Percentage of Subjects Who Achieve ALP of <1.5 x ULN at the End of Week 6 (Period 1)		Baseline to Week 6
Secondary	Percentage of Subjects Who Achieve a 50% Decrease in ALP at the End of Week 6 (Period 1)		Baseline to Week 6
Secondary	Percentage of Subjects Who Normalize ALP at the End of Week 6 (Period 1)		Baseline to Week 6
Secondary	Absolute Change in Serum Total Bilirubin at the End of Week 6 (Period 1)		Baseline to Week 6
Secondary	Absolute Change in Serum ALP From Week 6 to Week 12 (Period 2)		Week 6 to Week 12
Secondary	Percentage of Subjects Who Achieve ALP of <1.5 x ULN at the End of Week 12 (Period 2)		Week 6 to Week 12
Secondary	Percentage of Patients Who Achieve a 50% Decrease in ALP at the End of Week 12 (Period 2)		Week 6 to Week 12
Secondary	Percentage of Patients Who Normalize ALP at the End of Week 12 (Period 2)		Week 6 to Week 12
Secondary	Absolute Change in Serum Total Bilirubin at the End of Week 12 (Period 2)		Week 6 to Week 12
Secondary	Absolute Change in Serum ALP From Week 12 to Week 18 (Period 3)	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	Week 12 to Week 18
Secondary	Percentage of Patients Who Achieve ALP of <1.5 x ULN at the End of Week 18 (Period 3)	The percentage of patients who achieve ALP of <1.5 x ULN at the end of week 18 (Period 3)	Week 12 to Week 18
Secondary	Percentage of Patients Who Achieve a 50% Decrease in ALP at the End of Week 18 (Period 3)		Week 12 to Week 18
Secondary	Percentage of Subjects Who Normalize ALP at the End of Week 18 (Period 3)		Week 12 to Week 18
Secondary	Absolute Change in Serum Total Bilirubin at the End of Week 18 (Period 3)		Week 12 to Week 18