Study to Evaluate EP547 in Subjects With Cholestatic Pruritus Due to Primary Biliary Cholangitis or Primary Sclerosing Cholangitis (PACIFIC)

Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Effects of EP547 in Subjects With Cholestatic Pruritus Due to Primary Biliary Cholangitis or Primary Sclerosing Cholangitis

This phase 2 trial will evaluate the effects of EP547 in subjects with cholestatic pruritus due to Primary Biliary Cholangitis (PBC) or Primary Sclerosing Cholangitis (PSC)

Study Overview

• Status: Completed
• Conditions: Pruritus
• Intervention / Treatment: Drug: Placebo; Drug: EP547

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Antwerpen, Belgium
    • UZ Antwerpen
  • Gent, Belgium
    • UZ Gent
  • Leuven, Belgium
    • UZ Leuven
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2X8
      • University of Alberta
  • British Columbia
    • Vancouver, British Columbia, Canada
      • (G.I.R.I.) GI Research Institute
  • Ontario
    • Toronto, Ontario, Canada
      • Toronto Centre for Liver Disease Toronto General Hospital
  • Quebeck
    • Montreal, Quebeck, Canada, H2X 0A9
      • Centre hospitalier de l'Université de Montréal (CHUM)
• France
  • Bobigny, France
    • Aphp Avicenne
  • Grenoble, France
    • CHU Grenoble- Alpes- Site Nord
  • Lille, France
    • chu de Lille
  • Paris, France
    • Saint Antoine Hospital
  • Toulouse, France
    • Hospital Rangueil
  • Villejuif, France
    • Paul Brousse Hospital
• Israel
  • Haifa, Israel
    • Carmel Medical Center
  • Haifa, Israel
    • Rambam Medical Center- Keriat Eliezer Family Health Center
  • Jerusalem, Israel
    • Hadassah Medical Center (Ein-Karem)
  • Ramat Gan, Israel
    • Chaim Sheba Medical Center
• Netherlands
  • Amsterdam, Netherlands
    • Academic Medical Center- University of Amsterdam
• Spain
  • Alicante, Spain
    • Hospital General Universitario Alicante
  • Barcelona, Spain
    • Hospital Clinic Barcelona
  • Pontevedra, Spain
    • Hospital De Montecelo
  • Sevilla, Spain
    • Campus Hospital Universitario Virgen del Rocio
  • Valencia, Spain
    • La Fe University and Polytechnic Hospital
  • Zaragoza, Spain
    • Hospital Universitario Miguel Servet
• United Kingdom
  • Birmingham, United Kingdom
    • University Hospitals Birmingham NHS Foundation Trust
  • Glasgow, United Kingdom
    • Glasgow Royal Infirmary
  • London, United Kingdom
    • King's College Hospital NHS Foundation Trust
  • Newcastle, United Kingdom
    • Institute of Cellular Medicine, Newcastle University
  • Norwich, United Kingdom
    • Norfolk and Norwich University Hospitals NHS Foundation Trust
  • Nottingham, United Kingdom
    • University of Nottingham - Nottingham Digestive Diseases Centre Biomedical Research Unit
  • Plymouth, United Kingdom
    • University Hospitals Plymouth NHS Trust - Derriford Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama Birmingham Hospital
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Dignity Health Center for Clinical Research at St. Joseph Hospital
  • California
    • Coronado, California, United States, 92118
      • Southern California Research Center
    • Culver City, California, United States, 90230
      • Science 37
    • Pasadena, California, United States, 91105
      • California Liver Research Institute
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami - Schiff Center for Liver Diseases
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals & Clinics
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Health Sciences Center
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • New York, New York, United States, 10016
      • NYU Grossman School of Medicine Gastroenterology and Hepatology
  • Ohio
    • Cincinnati, Ohio, United States, 45249
      • Gastro Health Research
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Center for Liver Disease
  • Texas
    • Dallas, Texas, United States, 75203
      • The Liver Institute at Methodist Dallas Medical Center
    • Houston, Texas, United States, 77030
      • Liver Associates of Texas, PA
    • Katy, Texas, United States, 77494
      • Gastro health & Nutrition
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Digestive & Liver Disease Specialists
    • Richmond, Virginia, United States, 23226
      • Bon Secours Liver Institute of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18 to 80 years
• Documented primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC)
• Presence of consistent moderate to severe pruritus
• Use of anti-pruritic and anti-cholestatic (including UDCA and obeticholic acid) medication allowed if meeting additional criteria
• Individuals with concomitant inflammatory bowel disease must meet additional relevant criteria

Exclusion Criteria:

• Pruritus associated with an etiology other than PBC or PSC
• Prior or planned liver transplantation
• Evidence of compensated or decompensated cirrhosis
• Alternative causes of liver disease
• Presence of documented secondary sclerosing cholangitis
• Current evidence of clinically significant high-grade strictures or presence of biliary stent
• History of significant small bowel resection or short bowel syndrome
• Has exclusionary laboratory or biochemical results at Screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Once daily
Experimental: EP547 100 mg	Drug: EP547; Once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Worst Itch Numeric Rating Scale (WI-NRS) Score up to Week 6	Participants were asked to rate the severity of their worst level of itching in the past 24 hours using the daily WI-NRS, an 11-point scale ranging from 0 (no itching) to 10 (worst itching imaginable). Itching severity scores collected via the WI-NRS have been categorized in the as mild (<4), moderate (≥4 to <7), or severe (≥7). The average WI-NRS score using the daily values from the week before the first dose of study drug (including the WI-NRS score captured on Study Day 1 of dosing) served as the Baseline score. A weekly score was determined based on the average of all available daily scores of the week. Change from Baseline was calculated as the post-Baseline score minus the Baseline score.	Baseline; up to Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the 5-D Itch Scale Total Score at Week 6	The 5-D Itch Scale is a multidimensional (degree, duration, direction, disability, and distribution) questionnaire measuring changes in pruritis. The duration, degree, and direction domain scores range from 1 (no pruritus) to 5 (most severe pruritus). The disability domain includes 4 items assessing itching impact on daily activities: sleep, leisure/social activities, housework/errands, and work/school. Disability domain score=highest score on any of the 4 categories (1 [no pruritis] to 5 [most severe pruritis]). For the distribution domain, 16 body parts are listed to determine the distribution of itching over the last 2 weeks; the number of affected body parts is tallied (potential sum=0-16); the sum is sorted into 5 thresholds: 0-2 is assigned a score of 1; 3-5, a score of 2; 6-10, a score of 3; 11-13, a score of 4; 14-16, a score of 5. Higher scores indicate more severe pruritis. The 5 domain scores are summed to get a total 5-D score: 5 (no pruritus) to 25 (most severe pruritus).	Baseline; Week 6
Percentage of Participants With Improvement in Pruritus as Defined by Patient Global Impression of Change (PGI-C) at Week 6	Participants were asked to rate their impression of overall change in pruritus in the past 7 days compared to before they started taking study drug using the PGI-C, a 7-point scale ranging from "much improved" to "much worse," with higher scores indicating less improvement in pruritus. Participants that reported a change in their itch of "minimally improved" or better were considered to be responders in terms of "improvement in pruritus."	Baseline; Week 6
Percentage of Participants With Improvement in Pruritus Severity From Baseline as Defined by Change in Patient Global Impress of Severity (PGI-S) at Week 6	Participants were asked to rate the severity of their pruritus in the past 7 days using the PGI-S, a 4-point scale ranging from "none" to "severe." Participants that reported a positive shift in their categorical assessment of itch compared to their Baseline level (e.g., "severe" at Visit 2 [Day 1] with a shift to "moderate" at Visit 6 [Week 6]) were considered to be responders in terms of "improvement in pruritus."	Baseline; Week 6
Percentage of Participants With a Reduction in WI-NRS Score ≥2 From Baseline at Week 6	Participants were asked to rate the severity of their worst level of itching in the past 24 hours using the daily WI-NRS, an 11-point scale ranging from 0 (no itching) to 10 (worst itching imaginable). Itching severity scores collected via the WI-NRS have been categorized in the as mild (<4), moderate (≥4 to <7), or severe (≥7). The average WI-NRS score using the daily values from the week before the first dose of study drug (including the WI-NRS score captured on Study Day 1 of dosing) served as the Baseline score. A weekly score was determined based on the average of all available daily scores of the week.	Baseline; Week 6
Percentage of Participants With a Reduction in WI-NRS Score ≥3 From Baseline at Week 6	Participants were asked to rate the severity of their worst level of itching in the past 24 hours using the daily WI-NRS, an 11-point scale ranging from 0 (no itching) to 10 (worst itching imaginable). Itching severity scores collected via the WI-NRS have been categorized in the as mild (<4), moderate (≥4 to <7), or severe (≥7). The average WI-NRS score using the daily values from the week before the first dose of study drug (including the WI-NRS score captured on Study Day 1 of dosing) served as the Baseline score. A weekly score was determined based on the average of all available daily scores of the week.	Baseline; Week 6
Percentage of Participants With a Reduction in WI-NRS Score ≥4 From Baseline at Week 6	Participants were asked to rate the severity of their worst level of itching in the past 24 hours using the daily WI-NRS, an 11-point scale ranging from 0 (no itching) to 10 (worst itching imaginable). Itching severity scores collected via the WI-NRS have been categorized in the as mild (<4), moderate (≥4 to <7), or severe (≥7). The average WI-NRS score using the daily values from the week before the first dose of study drug (including the WI-NRS score captured on Study Day 1 of dosing) served as the Baseline score. A weekly score was determined based on the average of all available daily scores of the week.	Baseline; Week 6
Percentage of Participants With a WI-NRS Score <4 at Week 6	Participants were asked to rate the severity of their worst level of itching in the past 24 hours using the daily WI-NRS, an 11-point scale ranging from 0 (no itching) to 10 (worst itching imaginable). Itching severity scores collected via the WI-NRS have been categorized in the as mild (<4), moderate (≥4 to <7), or severe (≥7). The average WI-NRS score using the daily values from the week before the first dose of study drug (including the WI-NRS score captured on Study Day 1 of dosing) served as the Baseline score. A weekly score was determined based on the average of all available daily scores of the week.	Baseline; Week 6
Double-blind Treatment Period: Number of Participants With Any Treatment-emergent Adverse Event (TEAE), Any ≥Grade 3 TEAE, Any Related TEAE, and Any TEAE That Led to Discontinuation of Study Drug	An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable or unintended sign (including a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product. TEAEs are AEs with an onset after the first dose of study drug or existing events that worsened after the first dose during the study. TEAEs were graded for severity (mild [Grade 1], moderate [Grade 2], severe [Grade 3], life threatening [Grade 4], death [Grade 5]) using Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. The investigator assessed whether the TEAEs were related or unrelated to the study drug.	up to the end of Week 6
Open-label Extension Period: Number of Participants With Any TEAE, Any ≥Grade 3 TEAE, Any Related TEAE, and Any TEAE That Led to Discontinuation of Study Drug	An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable or unintended sign (including a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product. TEAEs are AEs with an onset after the first dose of study drug or existing events that worsened after the first dose during the study. TEAEs were graded for severity (mild [Grade 1], moderate [Grade 2], severe [Grade 3], life threatening [Grade 4], death [Grade 5]) using CTCAE, version 5.0. The investigator assessed whether the TEAEs were related or unrelated to the study drug.	from the beginning of Week 7 up to Week 12
Double-blind Treatment Period: Number of Participants With Any Serious TEAE, Any ≥Grade 3 Serious TEAE, Any Related Serious TEAE, and Any Serious TEAE That Led to Discontinuation of Study Drug	TEAEs are AEs with an onset after the first dose of study drug or existing events that worsened after the first dose during the study. A serious TEAE is any untoward medical occurrence, that at any dose: results in death; is life threatening; requires hospital admission or prolongs hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly/birth defect; or is a medically significant event that, based on appropriate medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent one of the previously listed outcomes. Serious TEAEs were graded for severity (mild [Grade 1], moderate [Grade 2], severe [Grade 3], life threatening [Grade 4], death [Grade 5]) using CTCAE, version 5.0. The investigator assessed whether the serious TEAEs were related or unrelated to the study drug.	up to the end of Week 6
Open-label Extension Period: Number of Participants With Any Serious TEAE, Any ≥Grade 3 Serious TEAE, Any Related Serious TEAE, and Any Serious TEAE That Led to Discontinuation of Study Drug	TEAEs are AEs with an onset after the first dose of study drug or existing events that worsened after the first dose during the study. A serious TEAE is any untoward medical occurrence, that at any dose: results in death; is life threatening; requires hospital admission or prolongs hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly/birth defect; or is a medically significant event that, based on appropriate medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent one of the previously listed outcomes. Serious TEAEs were graded for severity (mild [Grade 1], moderate [Grade 2], severe [Grade 3], life threatening [Grade 4], death [Grade 5]) using CTCAE, version 5.0. The investigator assessed whether the serious TEAEs were related or unrelated to the study drug.	from the beginning of Week 7 up to Week 12
Double-blind Treatment Period: Number of Participants With Any Treatment-emergent (TE) Adverse Event of Special Interest (AESI), Any ≥Grade 3 TE AESI, Any Related TE AESI, and Any TE AESI That Led to Discontinuation of Study Drug	An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. TEAEs are AEs with an onset after the first dose of study drug or existing events that worsened after the first dose during the study. AESI were considered to be any clinically meaningful new, worsening from Baseline, or abnormal laboratory findings or symptoms suggestive of acute kidney injury (AKI) (e.g., "blood urea increased" or "protein urine present" AEs as identified by the Standardized Medical Dictionary for Regulatory Activities [MedDRA] Query [SMQ] "Acute renal failure"). TE AESIs were graded for severity (mild [Grade 1], moderate [Grade 2], severe [Grade 3], life threatening [Grade 4], death [Grade 5]) using CTCAE, version 5.0. The investigator assessed whether the AE AESIs were related or unrelated to the study drug.	up to the end of Week 6
Open-label Extension Period: Number of Participants With Any Treatment-emergent (TE) AESI, Any ≥Grade 3 TE AESI, Any Related TE AESI, and Any TE AESI That Led to Discontinuation of Study Drug	An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. TEAEs are AEs with an onset after the first dose of study drug or existing events that worsened after the first dose during the study. AESI were considered to be any clinically meaningful new, worsening from Baseline, or abnormal laboratory findings or symptoms suggestive of acute kidney injury (AKI) (e.g., "blood urea increased" or "protein urine present" AEs as identified by the Standardized Medical Dictionary for Regulatory Activities [MedDRA] Query [SMQ] "Acute renal failure"). TE AESIs were graded for severity (mild [Grade 1], moderate [Grade 2], severe [Grade 3], life threatening [Grade 4], death [Grade 5]) using CTCAE, version 5.0. The investigator assessed whether the AE AESIs were related or unrelated to the study drug.	from the beginning of Week 7 up to Week 12
Number of Participants With Any Clinically Meaningful Changes From Baseline in Clinically Meaningful in Clinical Laboratory Test Results	Clinical laboratory test results included results for clinical hematology, chemistry, coagulation, and thyroid function parameters . The investigator determined if changes were clinically meaningful.	up to the end of Week 12
Number of Participants With Any Clinically Meaningful Changes From Baseline in Vital Sign Measurements	Vital sign measurements included measurements for blood pressure, pulse rate, oxygen saturation, body temperature, and respiratory rate. The investigator determined if changes were clinically meaningful.	up to the end of Week 12
Number of Participants With Any Clinically Significant Changes From Baseline in Electrocardiogram (ECG) Parameters	ECG parameters included heart rate, RR interval, PR interval, QRS duration, or QT interval. The investigator determined if changes were clinically significant.	up to the end of Week 12
Plasma Concentration of EP547 and Metabolites	The lower level of quantitation = 0.01 micrograms per milliliter (µg/mL) for EP547 and 0.005 μg/mL for EP3583.	1, 2, and 3 hours postdose on Day 1 and Week 3; predose on Weeks 1, 2, and 6

Collaborators and Investigators

• Sponsor: Escient Pharmaceuticals, Inc

Study record dates

Study Major Dates

• Study Start (Actual): October 6, 2022
• Primary Completion (Actual): July 17, 2024
• Study Completion (Actual): September 5, 2024

Study Registration Dates

• First Submitted: August 30, 2022
• First Submitted That Met QC Criteria: August 30, 2022
• First Posted (Actual): September 1, 2022

Study Record Updates

• Last Update Posted (Actual): July 31, 2025
• Last Update Submitted That Met QC Criteria: July 15, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Itch; Pruritus; Primary Sclerosing Cholangitis; Primary Biliary Cholangitis; PACIFIC; EP547
• Additional Relevant MeSH Terms: Pathologic Processes; Digestive System Diseases; Skin Manifestations; Biliary Tract Diseases; Liver Diseases; Skin Diseases; Bile Duct Diseases; Fibrosis; Cholestasis, Intrahepatic; Cholestasis; Liver Cirrhosis; Cholangitis; Cholangitis, Sclerosing; Liver Cirrhosis, Biliary; Pruritus
• Other Study ID Numbers: EP-547-201; 2021-002526-25 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No