Clinical trial NCT03333928: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Primary Sclerosing Cholangitis (PSC)
Lead sponsor: HighTide Biopharma Pty Ltd
Sponsor class: INDUSTRY
First posted: 2017-11-07
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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).
Primary purpose: TREATMENT

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.


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:

  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;

Primary outcomes:
measure: Absolute Change in Serum Alkaline Phosphatase (ALP) From Baseline to Week 6 in Period 1
timeFrame: Baseline to Week 6
Secondary outcomes:
measure: Percentage of Subjects Who Achieve ALP of <1.5 x ULN at the End of Week 6 (Period 1)
timeFrame: Baseline to Week 6
measure: Percentage of Subjects Who Achieve a 50% Decrease in ALP at the End of Week 6 (Period 1)
timeFrame: Baseline to Week 6
measure: Percentage of Subjects Who Normalize ALP at the End of Week 6 (Period 1)
timeFrame: Baseline to Week 6
measure: Absolute Change in Serum Total Bilirubin at the End of Week 6 (Period 1)
timeFrame: Baseline to Week 6
measure: Absolute Change in Serum ALP From Week 6 to Week 12 (Period 2)
timeFrame: Week 6 to Week 12
measure: Percentage of Subjects Who Achieve ALP of <1.5 x ULN at the End of Week 12 (Period 2)
timeFrame: Week 6 to Week 12
measure: Percentage of Patients Who Achieve a 50% Decrease in ALP at the End of Week 12 (Period 2)
timeFrame: Week 6 to Week 12
measure: Percentage of Patients Who Normalize ALP at the End of Week 12 (Period 2)
timeFrame: Week 6 to Week 12
measure: Absolute Change in Serum Total Bilirubin at the End of Week 12 (Period 2)
timeFrame: Week 6 to Week 12
measure: Absolute Change in Serum ALP From Week 12 to Week 18 (Period 3)
timeFrame: Week 12 to Week 18
measure: Percentage of Patients Who Achieve ALP of <1.5 x ULN at the End of Week 18 (Period 3)
timeFrame: Week 12 to Week 18
measure: Percentage of Patients Who Achieve a 50% Decrease in ALP at the End of Week 18 (Period 3)
timeFrame: Week 12 to Week 18
measure: Percentage of Subjects Who Normalize ALP at the End of Week 18 (Period 3)
timeFrame: Week 12 to Week 18
measure: Absolute Change in Serum Total Bilirubin at the End of Week 18 (Period 3)
timeFrame: Week 12 to Week 18
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Arizona Liver Health
state: Arizona
city: Tucson
country: United States
facility: Arizona Liver Health
state: Arizona
city: Fresno
country: United States
facility: Fresno Clinical Research Center
state: California
city: Los Angeles
country: United States
facility: Keck School of Medicine of USC
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado, Denver
state: Colorado
city: Englewood
country: United States
facility: South Denver Gastroenterology, PC
state: Colorado
city: New Haven
country: United States
facility: Yale School of Medicine
state: Connecticut
city: Lakewood Ranch
country: United States
facility: Florida Research Institute
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Baltimore
country: United States
facility: Mercy Medical Center
state: Maryland
city: Bethesda
country: United States
facility: Walter Reed National Military Medical Center
state: Maryland
city: Ann Arbor
country: United States
facility: Michigan Medicine University of Michigan
state: Michigan
city: Flowood
country: United States
facility: Gastrointestinal Associates
state: Mississippi
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Mount Sinai - Icahn School of Medicine
state: New York
city: Fayetteville
country: United States
facility: Cumberland Research Associates
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Germantown
country: United States
facility: Gastro One
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Austin
country: United States
facility: Pinnacle Clinical Research
state: Texas
city: San Antonio
country: United States
facility: Pinnacle Clinical Research
state: Texas
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Calgary
country: Canada
facility: Aspen Woods Clinic
state: Alberta
city: Toronto
country: Canada
facility: Toronto Centre for Liver Disease, Toronto General Hospital
state: Ontario
Study officials:
affiliation: HighTide Therapeutics USA, LLC
name: Adrian Di Bisceglie, MD,FACP,FAASLD
role: STUDY_DIRECTOR
References:
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.