Clinical trial NCT04604652: Open-Label Study of HTD1801 in Adult Subjects With Primary Biliary Cholangitis
Official title: 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Primary Biliary Cholangitis
Primary Biliary Cirrhosis
Cholangitis
Cholestasis
Biliary Tract Diseases
Bile Duct Stricture
Keywords: Open-label
Lead sponsor: HighTide Biopharma Pty Ltd
Sponsor class: INDUSTRY
First posted: 2020-10-27
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single group open label
Primary purpose: TREATMENT

Brief summary: The purpose of this open-label study is to evaluate the safety and tolerability of HDT1801 (BUDCA) over 12 weeks in adult subjects with PBC who have an inadequate response to standard therapy. Inadequate response is defined as persistently elevated serum alkaline phosphatase at greater than or equal to1.5 times the upper limits of normal for the testing lab in spite of having been on adequate doses of standard therapy with UDCA (ursodeoxycholic acid) at 13-15 mg/kg for at least 6 months.


Eligibility criteria: 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:

  1. Biochemical evidence of cholestasis with elevation of ALP activity
  2. Presence of antimitochondrial antibody (AMA)
  3. 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 cholestyramine 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

Primary outcomes:
measure: Percent Change in Alkaline Phosphatase (ALP) at Week 12 Compared to Baseline
timeFrame: Baseline to Week 12
Secondary outcomes:
measure: Change in Total Bilirubin From Baseline to Week 12
timeFrame: Baseline to Week 12
measure: Change in Serum Gamma-glutamyl Transferase (GGT) From Baseline to Week 12
timeFrame: Baseline to Week 12
measure: Change in Serum Total Cholesterol From Baseline to Week 12
timeFrame: Baseline to Week 12
measure: Change in Immunoglobulin M (IgM) From Baseline to Week 12
timeFrame: Baseline to Week 12
measure: Change in GLOBE Score Between Baseline and Week 12
timeFrame: Baseline to Week 12
measure: Change in Pruritus as Measured by Pruritus Visual Analog Score (VAS) From Baseline to Week 12
timeFrame: Baseline to Week 12.
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami Schiff Center for Liver Disease
state: Florida
city: Atlanta
country: United States
facility: Piedmont Healthcare
state: Georgia
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health Services
state: Michigan
city: Saint Louis
country: United States
facility: St. Louis University
state: Missouri
city: Manhasset
country: United States
facility: Northshore University Hospital
state: New York
city: Providence
country: United States
facility: University GI
state: Rhode Island
city: Dallas
country: United States
facility: Baylor Research Institute
state: Texas
city: San Antonio
country: United States
facility: The Texas Liver Institute
state: Texas
city: Newport News
country: United States
facility: Liver Institute of Virginia
state: Virginia
city: Richmond
country: United States
facility: Bon Secours Liver Institute of Richmond
state: Virginia
city: Seattle
country: United States
facility: Liver Institute Northwest
state: Washington
Study officials:
affiliation: HighTide Therapeutics Biopharma Pty.
name: Adrian DiBisceglie, MD
role: STUDY_DIRECTOR
References: