Trial Outcomes & Findings for Open-Label Study of HTD1801 in Adult Subjects With Primary Biliary Cholangitis (NCT NCT04604652)

NCT ID: NCT04604652

Last Updated: 2024-04-24

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 24 participants
• Primary outcome timeframe: Baseline to Week 12
• Results posted on: 2024-04-24

Participant Flow

A total of 46 subjects were screened of which 24 subjects were eligible and enrolled in the study. Subjects discontinued use of ursodeoxycholic acid (UDCA) at baseline prior to transitioning to HTD1801.

Participant milestones

Measure	HTD1801 1000 mg Twice Daily (BID) All subjects received HTD1801 1000 mg (4 x 250 mg tablets) administered orally twice daily (BID) with food for 12 weeks.
Overall Study STARTED	24
Overall Study COMPLETED	24
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	HTD1801 1000 mg BID n=24 Participants All subjects received HTD1801 1000 mg (4 x 250 mg tablets) administered orally twice daily with food for 12 weeks.
Age, Continuous	59.5 years STANDARD_DEVIATION 10.8 • n=5 Participants
Sex: Female, Male Female	22 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants
Race (NIH/OMB) White	22 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	24 participants n=5 Participants
Alkaline Phosphatase (ALP)	289.6 U/L STANDARD_DEVIATION 119.8 • n=5 Participants
Total Bilirubin	0.7 mg/dL STANDARD_DEVIATION 0.3 • n=5 Participants
Gamma-glutamyl Transferase (GGT)	211.0 U/L STANDARD_DEVIATION 187.6 • n=5 Participants
Total Cholesterol	216.7 mg/dL STANDARD_DEVIATION 47.8 • n=5 Participants
Immunoglobulin M (IgM)	340.6 mg/dL STANDARD_DEVIATION 246.1 • n=5 Participants
GLOBE score	0.3 units on a scale STANDARD_DEVIATION 0.7 • n=5 Participants
Pruritus Visual Analog Scale (VAS; average itch)	1.0 cm STANDARD_DEVIATION 1.6 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Week 12

Population: ITT Population: Included all subjects that received at least one dose of HTD1801

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.

Outcome measures

Measure	HTD1801 1000 mg BID n=20 Participants All subjects received HTD1801 1000 mg (4 x 250 mg tablets) administered orally twice daily with food for 12 weeks.
Percent Change in Alkaline Phosphatase (ALP) at Week 12 Compared to Baseline	-7.7 percent change Standard Deviation 23.3

SECONDARY outcome

Timeframe: Baseline to Week 12

Population: ITT Population

To evaluate the effects of HTD1801 on serum markers of cholestasis. A reduction in total bilirubin represents an improvement in a marker of cholestasis.

Outcome measures

Measure	HTD1801 1000 mg BID n=20 Participants All subjects received HTD1801 1000 mg (4 x 250 mg tablets) administered orally twice daily with food for 12 weeks.
Change in Total Bilirubin From Baseline to Week 12	-0.10 mg/dL Standard Deviation 0.20

SECONDARY outcome

Timeframe: Baseline to Week 12

Population: ITT Population

To evaluate the effects of HTD1801 on serum markers of cholestasis. A decrease in GGT represents an improvement in a marker of cholestasis.

Outcome measures

Measure	HTD1801 1000 mg BID n=20 Participants All subjects received HTD1801 1000 mg (4 x 250 mg tablets) administered orally twice daily with food for 12 weeks.
Change in Serum Gamma-glutamyl Transferase (GGT) From Baseline to Week 12	-34.1 U/L Standard Deviation 153.8

SECONDARY outcome

Timeframe: Baseline to Week 12

Population: ITT Population

To evaluate the effects of HTD1801 on serum lipids. A reduction in total cholesterol represents an improvement in serum lipids.

Outcome measures

Measure	HTD1801 1000 mg BID n=20 Participants All subjects received HTD1801 1000 mg (4 x 250 mg tablets) administered orally twice daily with food for 12 weeks.
Change in Serum Total Cholesterol From Baseline to Week 12	-18.8 mg/dL Standard Deviation 35.1

SECONDARY outcome

Timeframe: Baseline to Week 12

Population: ITT Population

To evaluate the effects of HTD1801 on serum markers of inflammation. A reduction in IgM represents an improvement in a marker of inflammation.

Outcome measures

Measure	HTD1801 1000 mg BID n=20 Participants All subjects received HTD1801 1000 mg (4 x 250 mg tablets) administered orally twice daily with food for 12 weeks.
Change in Immunoglobulin M (IgM) From Baseline to Week 12	-36.8 mg/dL Standard Deviation 71.4

SECONDARY outcome

Timeframe: Baseline to Week 12

Population: ITT Population

The GLOBE score is a validated risk assessment tool providing an estimate of transplant-free survival for patients with PBC. It was developed by the GLOBAL PBC Study Group using Cox regression model on over 4,000 patients with PBC. Lower GLOBE score predicts lower risk. It is calculated using age and levels of ALP, total bilirubin, platelets, and albumin.

Outcome measures

Measure	HTD1801 1000 mg BID n=20 Participants All subjects received HTD1801 1000 mg (4 x 250 mg tablets) administered orally twice daily with food for 12 weeks.
Change in GLOBE Score Between Baseline and Week 12	-0.07 units on a scale Standard Deviation 0.3

SECONDARY outcome

Timeframe: Baseline to Week 12.

Population: ITT Population

Pruritus Visual Analog Scale (VAS) is a self-reported instrument for measurement of itch intensity using 24-hour recall period. Subjects were asked to rate the average intensity of their itch on a 10 cm horizontal line ranging from 0 cm (no itch) to 10 cm (worst imaginable itch). A decrease in the Pruritus VAS represents an improvement in itch intensity.

Outcome measures

Measure	HTD1801 1000 mg BID n=20 Participants All subjects received HTD1801 1000 mg (4 x 250 mg tablets) administered orally twice daily with food for 12 weeks.
Change in Pruritus as Measured by Pruritus Visual Analog Score (VAS) From Baseline to Week 12	-0.9 units on a scale Standard Deviation 1.5

Adverse Events

HTD1801 1000 mg BID

Serious events: 1 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Measure	HTD1801 1000 mg BID n=24 participants at risk All subjects received HTD1801 1000 mg (4 x 250 mg tablets) administered orally twice daily with food for 12 weeks.
Infections and infestations COVID-19 Pneumonia	4.2% 1/24 • Number of events 1 • Adverse events were collected over a 16-week period, including a 12-week treatment period and 4-week followup.

Other adverse events

Measure	HTD1801 1000 mg BID n=24 participants at risk All subjects received HTD1801 1000 mg (4 x 250 mg tablets) administered orally twice daily with food for 12 weeks.
Gastrointestinal disorders Diarrhea	37.5% 9/24 • Adverse events were collected over a 16-week period, including a 12-week treatment period and 4-week followup.
Gastrointestinal disorders Abdominal Distension	16.7% 4/24 • Adverse events were collected over a 16-week period, including a 12-week treatment period and 4-week followup.
Gastrointestinal disorders Vomiting	12.5% 3/24 • Adverse events were collected over a 16-week period, including a 12-week treatment period and 4-week followup.
Gastrointestinal disorders Abdominal Pain Upper	8.3% 2/24 • Adverse events were collected over a 16-week period, including a 12-week treatment period and 4-week followup.
Gastrointestinal disorders Constipation	8.3% 2/24 • Adverse events were collected over a 16-week period, including a 12-week treatment period and 4-week followup.
Gastrointestinal disorders Nausea	8.3% 2/24 • Adverse events were collected over a 16-week period, including a 12-week treatment period and 4-week followup.
General disorders Pyrexia	8.3% 2/24 • Adverse events were collected over a 16-week period, including a 12-week treatment period and 4-week followup.
Infections and infestations Bronchitis	8.3% 2/24 • Adverse events were collected over a 16-week period, including a 12-week treatment period and 4-week followup.
Infections and infestations Upper Respiratory Tract Infection	8.3% 2/24 • Adverse events were collected over a 16-week period, including a 12-week treatment period and 4-week followup.
Investigations Liver Function Test Increased	16.7% 4/24 • Adverse events were collected over a 16-week period, including a 12-week treatment period and 4-week followup.
Investigations Alanine Aminotransferase Increased	8.3% 2/24 • Adverse events were collected over a 16-week period, including a 12-week treatment period and 4-week followup.
Investigations Aspartate Aminotransferase Increased	8.3% 2/24 • Adverse events were collected over a 16-week period, including a 12-week treatment period and 4-week followup.
Metabolism and nutrition disorders Decreased Appetite	8.3% 2/24 • Adverse events were collected over a 16-week period, including a 12-week treatment period and 4-week followup.
Musculoskeletal and connective tissue disorders Arthralgia	8.3% 2/24 • Adverse events were collected over a 16-week period, including a 12-week treatment period and 4-week followup.
Nervous system disorders Headache	12.5% 3/24 • Adverse events were collected over a 16-week period, including a 12-week treatment period and 4-week followup.
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	8.3% 2/24 • Adverse events were collected over a 16-week period, including a 12-week treatment period and 4-week followup.
Skin and subcutaneous tissue disorders Pruritus	20.8% 5/24 • Adverse events were collected over a 16-week period, including a 12-week treatment period and 4-week followup.

Additional Information

VP Clinical Operations

HighTide Therapeutics

Phone: 760-809-3523

Email: cbennett@hightidetx.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place