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

Primary Purpose

Primary Sclerosing Cholangitis (PSC)

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
HTD1801
Placebo
Sponsored by
HighTide Biopharma Pty Ltd
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Sclerosing Cholangitis (PSC)

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept 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;

Sites / Locations

  • Arizona Liver Health
  • Arizona Liver Health
  • Fresno Clinical Research Center
  • Keck School of Medicine of USC
  • Cedars-Sinai Medical Center
  • University of Colorado, Denver
  • South Denver Gastroenterology, PC
  • Yale School of Medicine
  • Florida Research Institute
  • University of Miami
  • Mercy Medical Center
  • Walter Reed National Military Medical Center
  • Michigan Medicine University of Michigan
  • Gastrointestinal Associates
  • Washington University School of Medicine
  • Mount Sinai - Icahn School of Medicine
  • Cumberland Research Associates
  • Wake Forest Baptist Health
  • Gastro One
  • Vanderbilt University Medical Center
  • Pinnacle Clinical Research
  • Pinnacle Clinical Research
  • Swedish Medical Center
  • University of Washington
  • Aspen Woods Clinic
  • Toronto Centre for Liver Disease, Toronto General Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Placebo Comparator

Arm Label

HTD1801 500 mg BID

HTD1801 1000 mg BID

Placebo BID

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
October 27, 2017
Last Updated
March 13, 2022
Sponsor
HighTide Biopharma Pty Ltd
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1. Study Identification

Unique Protocol Identification Number
NCT03333928
Brief Title
A POC and Dose-Ranging Study of HTD1801 in PSC Patients
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)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
February 9, 2018 (Actual)
Primary Completion Date
April 30, 2020 (Actual)
Study Completion Date
August 14, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
HighTide Biopharma Pty Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Sclerosing Cholangitis (PSC)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
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
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
59 (Actual)

8. Arms, Groups, and Interventions

Arm Title
HTD1801 500 mg BID
Arm Type
Active Comparator
Arm Title
HTD1801 1000 mg BID
Arm Type
Active Comparator
Arm Title
Placebo BID
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
HTD1801
Intervention Description
HTD1801 tablets, 250 mg
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
tablets manufactured to mimic HTD1801 tablets
Primary Outcome Measure Information:
Title
Absolute Change in Serum Alkaline Phosphatase (ALP) From Baseline to Week 6 in Period 1
Time Frame
Baseline to Week 6
Secondary Outcome Measure Information:
Title
Percentage of Subjects Who Achieve ALP of <1.5 x ULN at the End of Week 6 (Period 1)
Time Frame
Baseline to Week 6
Title
Percentage of Subjects Who Achieve a 50% Decrease in ALP at the End of Week 6 (Period 1)
Time Frame
Baseline to Week 6
Title
Percentage of Subjects Who Normalize ALP at the End of Week 6 (Period 1)
Time Frame
Baseline to Week 6
Title
Absolute Change in Serum Total Bilirubin at the End of Week 6 (Period 1)
Time Frame
Baseline to Week 6
Title
Absolute Change in Serum ALP From Week 6 to Week 12 (Period 2)
Time Frame
Week 6 to Week 12
Title
Percentage of Subjects Who Achieve ALP of <1.5 x ULN at the End of Week 12 (Period 2)
Time Frame
Week 6 to Week 12
Title
Percentage of Patients Who Achieve a 50% Decrease in ALP at the End of Week 12 (Period 2)
Time Frame
Week 6 to Week 12
Title
Percentage of Patients Who Normalize ALP at the End of Week 12 (Period 2)
Time Frame
Week 6 to Week 12
Title
Absolute Change in Serum Total Bilirubin at the End of Week 12 (Period 2)
Time Frame
Week 6 to Week 12
Title
Absolute Change in Serum ALP From Week 12 to Week 18 (Period 3)
Description
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
Time Frame
Week 12 to Week 18
Title
Percentage of Patients Who Achieve ALP of <1.5 x ULN at the End of Week 18 (Period 3)
Description
The percentage of patients who achieve ALP of <1.5 x ULN at the end of week 18 (Period 3)
Time Frame
Week 12 to Week 18
Title
Percentage of Patients Who Achieve a 50% Decrease in ALP at the End of Week 18 (Period 3)
Time Frame
Week 12 to Week 18
Title
Percentage of Subjects Who Normalize ALP at the End of Week 18 (Period 3)
Time Frame
Week 12 to Week 18
Title
Absolute Change in Serum Total Bilirubin at the End of Week 18 (Period 3)
Time Frame
Week 12 to Week 18

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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: 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. 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;
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Adrian Di Bisceglie, MD,FACP,FAASLD
Organizational Affiliation
HighTide Therapeutics USA, LLC
Official's Role
Study Director
Facility Information:
Facility Name
Arizona Liver Health
City
Chandler
State/Province
Arizona
ZIP/Postal Code
85224
Country
United States
Facility Name
Arizona Liver Health
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85711
Country
United States
Facility Name
Fresno Clinical Research Center
City
Fresno
State/Province
California
ZIP/Postal Code
93720
Country
United States
Facility Name
Keck School of Medicine of USC
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
University of Colorado, Denver
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
South Denver Gastroenterology, PC
City
Englewood
State/Province
Colorado
ZIP/Postal Code
80113
Country
United States
Facility Name
Yale School of Medicine
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
Florida Research Institute
City
Lakewood Ranch
State/Province
Florida
ZIP/Postal Code
34211
Country
United States
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Mercy Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21202
Country
United States
Facility Name
Walter Reed National Military Medical Center
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20889
Country
United States
Facility Name
Michigan Medicine University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Gastrointestinal Associates
City
Flowood
State/Province
Mississippi
ZIP/Postal Code
39232
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Mount Sinai - Icahn School of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Cumberland Research Associates
City
Fayetteville
State/Province
North Carolina
ZIP/Postal Code
28304
Country
United States
Facility Name
Wake Forest Baptist Health
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
Gastro One
City
Germantown
State/Province
Tennessee
ZIP/Postal Code
38138
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37212
Country
United States
Facility Name
Pinnacle Clinical Research
City
Austin
State/Province
Texas
ZIP/Postal Code
78746
Country
United States
Facility Name
Pinnacle Clinical Research
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Swedish Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
University of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
Aspen Woods Clinic
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T3H 0V5
Country
Canada
Facility Name
Toronto Centre for Liver Disease, Toronto General Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2C4
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
36327436
Citation
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.
Results Reference
derived

Learn more about this trial

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

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