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

NCT03333928 | Completed Phase 2 Results FDA Drug

• 1 other identifier: HTD1801.PCT003
• Study Type: interventional
• Target: 59
• Locations: 2 countries
• Sites: 26

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.

Conditions

Primary Sclerosing Cholangitis (PSC)

Outcome Measures

Primary Outcomes (1)

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

  Baseline to Week 6

Secondary Outcomes (14)

• 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

Study Arms (3)

HTD1801 500 mg BID

ACTIVE COMPARATOR

Drug: HTD1801

HTD1801 1000 mg BID

ACTIVE COMPARATOR

Drug: HTD1801

Placebo BID

PLACEBO COMPARATOR

Drug: Placebo

Interventions

HTD1801 DRUG

HTD1801 tablets, 250 mg

HTD1801 1000 mg BID; HTD1801 500 mg BID

Placebo DRUG

tablets manufactured to mimic HTD1801 tablets

Placebo BID

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• amino salicylic acid drugs,
• azathioprine,
• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• HighTide Biopharma Pty Ltd: lead

Study Sites (26)

Arizona Liver Health

Chandler, Arizona, 85224, United States

Location

Arizona Liver Health

Tuscon, Arizona, 85711, United States

Location

Fresno Clinical Research Center

Fresno, California, 93720, United States

Location

Keck School of Medicine of USC

Los Angeles, California, 90033, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

University of Colorado, Denver

Aurora, Colorado, 80045, United States

Location

South Denver Gastroenterology, PC

Englewood, Colorado, 80113, United States

Location

Yale School of Medicine

New Haven, Connecticut, 06520, United States

Location

Florida Research Institute

Lakewood Rch, Florida, 34211, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Mercy Medical Center

Baltimore, Maryland, 21202, United States

Location

Walter Reed National Military Medical Center

Bethesda, Maryland, 20889, United States

Location

Michigan Medicine University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Gastrointestinal Associates

Flowood, Mississippi, 39232, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Mount Sinai - Icahn School of Medicine

New York, New York, 10029, United States

Location

Cumberland Research Associates

Fayetteville, North Carolina, 28304, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

Location

Gastro One

Germantown, Tennessee, 38138, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37212, United States

Location

Pinnacle Clinical Research

Austin, Texas, 78746, United States

Location

Pinnacle Clinical Research

San Antonio, Texas, 78229, United States

Location

Swedish Medical Center

Seattle, Washington, 98104, United States

Location

University of Washington

Seattle, Washington, 98104, United States

Location

Aspen Woods Clinic

Calgary, Alberta, T3H 0V5, Canada

Location

Toronto Centre for Liver Disease, Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

Related Publications (1)

• 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.

  PMID: 36327436 DERIVED

MeSH Terms

Conditions

Cholangitis, Sclerosing

Condition Hierarchy (Ancestors)

Cholangitis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases

Results Point of Contact

• Title: Dr. Adrian Di Bisceglie, CMO
• Organization: HighTide Therapeutics

adibisceglie@hightidetx.com

314-791-0593

Study Officials

• Adrian Di Bisceglie, MD,FACP,FAASLD

  HighTide Therapeutics USA, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: October 27, 2017
• First Posted: November 7, 2017
• Study Start: February 9, 2018
• Primary Completion: April 30, 2020
• Study Completion: August 14, 2020
• Last Updated: October 23, 2025
• Results First Posted: April 6, 2022

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2); US (24)