Open-Label Study of HTD1801 in Adult Subjects With Primary Biliary Cholangitis

NCT04604652 | Completed Phase 2 Results FDA Drug

• 1 other identifier: HTD1801.PCT013
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 12

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.

Conditions

Primary Biliary Cholangitis; Primary Biliary Cirrhosis; Cholangitis; Cholestasis; Biliary Tract Diseases; Bile Duct Stricture

Keywords

Open-label

Outcome Measures

Primary Outcomes (1)

• Percent Change in Alkaline Phosphatase (ALP) at Week 12 Compared to Baseline

  To evaluate the effects of HTD1801 on serum ALP in adult subjects with PBC who have experienced an inadequate response to standard therapy. Inadequate response is defined as ALP ≥1.5 × upper limit of normal (ULN) despite having been on adequate doses of ursodeoxycholic acid (UDCA) for at least 6 months. A reduction in ALP represents an improvement.

  Baseline to Week 12

Secondary Outcomes (6)

• Change in Total Bilirubin From Baseline to Week 12

  Baseline to Week 12

• Change in Serum Gamma-glutamyl Transferase (GGT) From Baseline to Week 12

  Baseline to Week 12

• Change in Serum Total Cholesterol From Baseline to Week 12

  Baseline to Week 12

• Change in Immunoglobulin M (IgM) From Baseline to Week 12

  Baseline to Week 12

• Change in GLOBE Score Between Baseline and Week 12

  Baseline to Week 12

Study Arms (1)

Open-label

EXPERIMENTAL

HTD1801 (BUDCA) 250 mg tablets. Dosed at 1000 mg BID with food.

Drug: HTD1801 (BUDCA)

Interventions

HTD1801 (BUDCA) DRUG

HTD1801 (BUDCA) 250 mg tablets. Dose 1000 mg twice daily with food for 12 weeks.

Open-label

Eligibility Criteria

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

You may qualify if:

• 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 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

You may not qualify if:

• 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

Sponsors & Collaborators

• HighTide Biopharma Pty Ltd: lead

Study Sites (12)

University of Miami Schiff Center for Liver Disease

Miami, Florida, 33136, United States

Location

Piedmont Healthcare

Atlanta, Georgia, 30309, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Henry Ford Health Services

Detroit, Michigan, 48202, United States

Location

St. Louis University

St Louis, Missouri, 63104, United States

Location

Northshore University Hospital

Manhasset, New York, 11030, United States

Location

University GI

Providence, Rhode Island, 02905, United States

Location

Baylor Research Institute

Dallas, Texas, 75246, United States

Location

The Texas Liver Institute

San Antonio, Texas, 78215, United States

Location

Liver Institute of Virginia

Newport News, Virginia, 23602, United States

Location

Bon Secours Liver Institute of Richmond

Richmond, Virginia, 23226, United States

Location

Liver Institute Northwest

Seattle, Washington, 98105, United States

Location

MeSH Terms

Conditions

Liver Cirrhosis, Biliary; Cholangitis; Cholestasis; Biliary Tract Diseases

Condition Hierarchy (Ancestors)

Cholestasis, Intrahepatic; Bile Duct Diseases; Digestive System Diseases; Liver Diseases; Liver Cirrhosis; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

This was a small, open-label, proof of concept study with no control group where subjects discontinued UDCA at Baseline. Limitations of the study include potentially being underpowered for the primary endpoint and the safety included adverse events from the 4-week follow-up period after treatment discontinuation. Additional placebo-controlled studies are needed to further evaluate the benefit of HTD1801 in PBC.

Results Point of Contact

• Title: VP Clinical Operations
• Organization: HighTide Therapeutics

cbennett@hightidetx.com

760-809-3523

Study Officials

• Adrian DiBisceglie, MD

  HighTide Therapeutics Biopharma Pty.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single group open label

Study Record Dates

• First Submitted: October 16, 2020
• First Posted: October 27, 2020
• Study Start: May 27, 2021
• Primary Completion: May 31, 2022
• Study Completion: May 31, 2022
• Last Updated: April 24, 2024
• Results First Posted: April 24, 2024

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (12)