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

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

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.

Study Overview

• Status: Completed
• Conditions: Primary Sclerosing Cholangitis (PSC)
• Intervention / Treatment: Drug: HTD1801; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3H 0V5
      • Aspen Woods Clinic
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto Centre for Liver Disease, Toronto General Hospital
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Arizona Liver Health
    • Tucson, Arizona, United States, 85711
      • Arizona Liver Health
  • California
    • Fresno, California, United States, 93720
      • Fresno Clinical Research Center
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Los Angeles, California, United States, 90033
      • Keck School of Medicine of USC
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado, Denver
    • Englewood, Colorado, United States, 80113
      • South Denver Gastroenterology, PC
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale School of Medicine
  • Florida
    • Lakewood Ranch, Florida, United States, 34211
      • Florida Research Institute
    • Miami, Florida, United States, 33136
      • University of Miami
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • Mercy Medical Center
    • Bethesda, Maryland, United States, 20889
      • Walter Reed National Military Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Michigan Medicine University of Michigan
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Gastrointestinal Associates
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai - Icahn School of Medicine
  • North Carolina
    • Fayetteville, North Carolina, United States, 28304
      • Cumberland Research Associates
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Health
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Gastro One
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center
  • Texas
    • Austin, Texas, United States, 78746
      • Pinnacle Clinical Research
    • San Antonio, Texas, United States, 78229
      • Pinnacle Clinical Research
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Medical Center
    • Seattle, Washington, United States, 98104
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo BID	Drug: Placebo; tablets manufactured to mimic HTD1801 tablets
Active Comparator: HTD1801 500 mg BID	Drug: HTD1801; HTD1801 tablets, 250 mg
Active Comparator: HTD1801 1000 mg BID	Drug: HTD1801; HTD1801 tablets, 250 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Absolute Change in Serum Alkaline Phosphatase (ALP) From Baseline to Week 6 in Period 1	Baseline to Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Subjects Who Achieve a 50% Decrease in ALP at the End of Week 6 (Period 1)		Baseline to Week 6
Percentage of Subjects Who Normalize ALP at the End of Week 6 (Period 1)		Baseline to Week 6
Absolute Change in Serum Total Bilirubin 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 Subjects Who Achieve ALP of <1.5 x ULN 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 12 (Period 2)		Week 6 to Week 12
Percentage of Patients Who Normalize ALP at the End of Week 12 (Period 2)		Week 6 to Week 12
Absolute Change in Serum Total Bilirubin at the End of Week 12 (Period 2)		Week 6 to Week 12
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
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
Percentage of Patients Who Achieve a 50% Decrease in ALP at the End of Week 18 (Period 3)		Week 12 to Week 18
Percentage of Subjects Who Normalize ALP at the End of Week 18 (Period 3)		Week 12 to Week 18
Absolute Change in Serum Total Bilirubin at the End of Week 18 (Period 3)		Week 12 to Week 18

Collaborators and Investigators

• Sponsor: HighTide Biopharma Pty Ltd

Publications and helpful links

General Publications

• Kowdley KV, Forman L, Eksteen B, Gunn N, Sundaram V, Landis C, Harrison SA, Levy C, Liberman A, Di Bisceglie AM, Hirschfield GM. A Randomized, Dose-Finding, Proof-of-Concept Study of Berberine Ursodeoxycholate in Patients With Primary Sclerosing Cholangitis. Am J Gastroenterol. 2022 Nov 1;117(11):1805-1815. doi: 10.14309/ajg.0000000000001956. Epub 2022 Aug 22.

Study record dates

Study Major Dates

• Study Start (Actual): February 9, 2018
• Primary Completion (Actual): April 30, 2020
• Study Completion (Actual): August 14, 2020

Study Registration Dates

• First Submitted: October 27, 2017
• First Submitted That Met QC Criteria: November 5, 2017
• First Posted (Actual): November 7, 2017

Study Record Updates

• Last Update Posted (Actual): April 6, 2022
• Last Update Submitted That Met QC Criteria: March 13, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Biliary Tract Diseases; Bile Duct Diseases; Cholangitis; Cholangitis, Sclerosing
• Other Study ID Numbers: HTD1801.PCT003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No