- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04604652
Open-Label Study of HTD1801 in Adult Subjects With Primary Biliary Cholangitis (PRONTO-PBC)
A Phase 2 Open Label, Proof of Concept Study of HTD1801 (BUDCA) in Adult Subjects With Primary Biliary Cholangitis (PBC) and an Inadequate Response to Standard Therapy - PRONTO-PBC
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Florida
-
Miami, Florida, United States, 33136
- University of Miami Schiff Center for Liver Disease
-
-
Georgia
-
Atlanta, Georgia, United States, 30309
- Piedmont Healthcare
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02114
- Massachusetts General Hospital
-
-
Michigan
-
Detroit, Michigan, United States, 48202
- Henry Ford Health Services
-
-
Missouri
-
Saint Louis, Missouri, United States, 63104
- St. Louis University
-
-
New York
-
Manhasset, New York, United States, 11030
- Northshore University Hospital
-
-
Rhode Island
-
Providence, Rhode Island, United States, 02905
- University GI
-
-
Texas
-
Dallas, Texas, United States, 75246
- Baylor Research Institute
-
San Antonio, Texas, United States, 78215
- The Texas Liver Institute
-
-
Virginia
-
Newport News, Virginia, United States, 23602
- Liver Institute of Virginia
-
Richmond, Virginia, United States, 23226
- Bon Secours Liver Institute of Richmond
-
-
Washington
-
Seattle, Washington, United States, 98105
- Liver Institute Northwest
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Have a clinical diagnosis of PBC as confirmed by patient history consistent with the American Association for the Study of Liver Diseases (AASLD) Practice Guideline confirmed by two of the following three criteria:
- Biochemical evidence of cholestasis with elevation of ALP activity
- Presence of antimitochondrial antibody (AMA)
- Histopathologic evidence of non-suppurative cholangitis and destruction of small or medium-sized bile ducts if biopsy performed Note: historical AMA and liver biopsy data may be used but must be recorded in source documentation.
- Has been taking a stable, adequate dose of at least (13-15 mg/kg/day) of UDCA for at least 6 months with a serum ALP of at least ≥1.5 × ULN at any time after being on UDCA for >6 months (historical value) and at Screening. If the historical ALP was obtained less than 6 months prior to study start as part of standard of care, the subject may be screened and a second ALP value should be obtained as part of screening, There must be at least a 4-week interval between the ALP values and the ALP values must be ≥1.5 × ULN
- If the subject is taking cholestramine or other bile acid sequestrant for pruritus, must be on a stable dose no more than once a day for at least 8 weeks prior to Baseline visit. Must be willing and able to take cholestyramine at least 2 hours before or after study medication
- Females of child-bearing potential and males participating in the study must either agree to use at least two approved barrier methods of contraception or be completely abstinent from sexual intercourse, if this is their usual and preferred lifestyle, throughout the duration of the study and for three months after stopping study drug. Females who are postmenopausal must have appropriate documentation
- Able to provide consent
Exclusion Criteria:
- Uncontrolled concomitant autoimmune hepatitis (AIH). Subject should be on no more than 5 mg per day of prednisone (or equivalent dose for other corticosteroids) or no more than 150 mg per day of azathioprine at stable doses and serum ALT should be ≤ 5 × ULN. Enrollment of subjects with controlled AIH will be limited to a total of 5 subjects.
- History of alcohol or substance abuse
- Prior liver transplantation or currently listed for liver transplantation
- History of chronic viral hepatitis, types B or C
- Platelet count ≤150,000/mm3, albumin <3.0 g/dL, International Normalized Ratio (INR) >1.2, or a history of ascites, or encephalopathy, or history of variceal bleeding
- Total bilirubin >1.3 × ULN unless subject has Gilbert Syndrome. If subject has increased total bilirubin due to Gilbert's Syndrome, then direct bilirubin should be <0.3 mg/dL.
- Hemoglobin <10 g/dL for males or females
- Serum TSH level <0.1 or >10 u/mL (subject may be re-screened if hyper- or hypothyroidism has been corrected)
- Renal impairment with eGFR <60 ml/min (CKD stages 3, 4 or 5)
- Human immunodeficiency virus (HIV)-1 or HIV-2 infection by history
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency
- History of malignancy within the past 2 years or ongoing malignancy other than basal cell carcinoma, or resected noninvasive cutaneous squamous cell carcinoma
- Active, serious infections that require parenteral antibiotic or antifungal therapy within 30 days prior to Screening
- Major surgical procedure within 30 days of Screening or prior solid organ transplantation
- Females who are pregnant or breastfeeding
- Current or anticipated treatment with radiation therapy, cytotoxic chemotherapeutic agents, and immune-modulating agents (such as interleukins, interferons)
- Diseases that may result in increased serum ALP activities from sources other than the biliary system (e.g., Paget's disease of bone, osteomalacia)
- Allergy to the clinical trial material or its components
- Having received any experimental medications within 28 days prior to Screening
- Use of bezafibrate or fenofibrate within 28 days prior to first day of IP dosing
- Use of obeticholic acid (OCA) within 28 days prior to first day of IP dosing
- Any other clinically significant disorders or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for the study or unable to comply with the dosing and protocol requirements
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Open-label
HTD1801 (BUDCA) 250 mg tablets.
Dosed at 1000 mg BID with food.
|
HTD1801 (BUDCA) 250 mg tablets.
Dose 1000 mg twice daily with food for 12 weeks.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percent change in alkaline phosphatase at Week 12 compared to Baseline
Time Frame: 12 weeks
|
To evaluate the effects of HTD1801 (BUDCA) on serum alkaline phosphatase (ALP) in adult subjects with PBC who have experienced an inadequate response to standard therapy. Inadequate response is defined as ALP ≥1.5 × ULN despite having been on adequate doses of UDCA for at least 6 months |
12 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in serum bilirubin from Baseline to Week 12
Time Frame: 12 weeks
|
To evaluate the effects of HTD1801 (BUDCA) on serum markers of cholestasis
|
12 weeks
|
Change in serum gamma-glutamyl transferase (GGT) between Baseline and Week
Time Frame: 12 weeks
|
To evaluate the effects of HTD1801 (BUDCA) on serum markers of cholestasis
|
12 weeks
|
Change in serum cholesterol (total and LDL) and triglyceride levels between Baseline and Week 12
Time Frame: 12 weeks
|
To evaluate the effects of HTD1801 on serum lipids
|
12 weeks
|
Change in inflammatory serum markers including fibrinogen, CRP, Haptoglobin, ELF and serum immunoglobulins between Baseline and Week 12
Time Frame: 12 weeks
|
To evaluate the effects of HTD1801 (BUDCA) on serum markers of inflammation
|
12 weeks
|
Change in GLOBE score between Baseline and Week 12
Time Frame: 12 weeks
|
To evaluate the safety and tolerability of HTD1801 over 12 weeks of treatment in adult subjects with PBC
|
12 weeks
|
Change in pruritus as measured by Pruritus visual analog score (VAS) between Baseline and Week 12
Time Frame: 12 weeks
|
To evaluate the safety and tolerability of HTD1801 over 12 weeks of treatment in adult subjects with PBC
|
12 weeks
|
Adverse events and changes in physical examination, vital signs, and clinical laboratory values
Time Frame: 12 weeks
|
To evaluate the safety and tolerability of HTD1801 over 12 weeks of treatment in adult subjects with PBC
|
12 weeks
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Adrian DiBisceglie, MD, HighTide Therapeutics Biopharma Pty.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- HTD1801.PCT013
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Biliary Tract Diseases
-
Sun Yat-sen UniversityJiangsu Hengrui Pharmaceutical Co., Ltd.Not yet recruitingMetastatic Biliary Tract Cancer | Locally Advanced Biliary Tract CancerChina
-
Second Military Medical UniversityUnknownAdvanced Biliary Tract Malignant TumorChina
-
Gyeongsang National University HospitalSamsung Medical Center; Dong-A University; Chung-Ang UniversityTerminatedMetastatic Biliary Tract Cancer | Locally Advanced Biliary Tract CancerKorea, Republic of
-
AstraZenecaActive, not recruiting
-
Peking Union Medical College HospitalRecruitingBiliary Tract Neoplasms ImmunotherapyChina
-
Peking Union Medical College HospitalRecruitingBiliary Tract Neoplasms ImmunotherapyChina
-
Fudan UniversityRecruitingAdvanced Biliary Tract CancerChina
-
Innovent Biologics (Suzhou) Co. Ltd.RecruitingAdvanced Biliary Tract CancerChina
-
Tianjin Medical University Cancer Institute and...RecruitingResectable Biliary Tract CancerChina
-
University of Kansas Medical CenterRecruitingAdvanced Biliary Tract CancerUnited States
Clinical Trials on HTD1801 (BUDCA)
-
HighTide Biopharma Pty LtdCompletedDigestive System Diseases | NAFLD | Nonalcoholic Fatty Liver Disease | Nonalcoholic Steatohepatitis | Type 2 Diabetes Mellitus (T2DM) | Fatty Liver, NonalcoholicUnited States
-
HighTide Biopharma Pty LtdCompletedHypercholesterolemiaAustralia
-
HighTide Biopharma Pty LtdCompleted
-
HighTide Biopharma Pty LtdCompletedPrimary Sclerosing Cholangitis (PSC)United States, Canada
-
HighTide Biopharma Pty LtdActive, not recruitingType 2 Diabetes | Nonalcoholic Steatohepatitis (NASH)United States, China, Hong Kong
-
HighTide Biopharma Pty LtdWithdrawnAdolescent | Digestive System Diseases | Biliary Tract Diseases | Primary Sclerosing Cholangitis | Cholangitis | Cholangitis, Sclerosing | Bile Duct Diseases
-
HighTide Biopharma Pty LtdRecruitingT2DM (Type 2 Diabetes Mellitus)China
-
HighTide Biopharma Pty LtdRecruiting