A Trial of Setanaxib in Patients With Primary Biliary Cholangitis (PBC) and Liver Stiffness (TRANSFORM)

TRANSFORM: A 24-week, Randomized, Placebo-controlled, Double-blind, Phase 2b Trial of Setanaxib in Patients With Primary Biliary Cholangitis (PBC) and Elevated Liver Stiffness

The primary objective of this study is to evaluate the effect of setanaxib on alkaline phosphatase (ALP) at Week 24 in participants with PBC and with elevated liver stiffness and intolerance or inadequate response to ursodeoxycholic acid (UDCA).

Study Overview

• Status: Completed
• Conditions: Primary Biliary Cholangitis; Liver Stiffness
• Intervention / Treatment: Drug: Placebo; Drug: Setanaxib

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Kingswood, Australia, 2747
    • Nepean Hospital
  • Liverpool, Australia, 2170
    • Liverpool Hospital
  • Melbourne, Australia, 3004
    • The Alfred Hospital
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
    • New Lambton Heights, New South Wales, Australia, 2305
      • John Hunter Hospital
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Mater Misericordiae - Hospital Brisbane
  • South Australia
    • Bedford Park, South Australia, Australia, 5042
      • Flinders Medical Centre
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Eastern Health - Australia
    • Clayton, Victoria, Australia, 3168
      • Monash Medical Centre
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Fiona Stanley Hospital
• Austria
  • Oberösterreich
    • Linz, Oberösterreich, Austria, 4010
      • Ordensklinikum Linz GmbH Barmherzige Schwestern
    • Wels, Oberösterreich, Austria, 4600
      • Klinikum Wels-Grieskirchen
  • Styria
    • Graz, Styria, Austria, 8036
      • Universitaetsklinikum Graz - Universitätsklinik für Innere Medizin
  • Tyrol
    • Innsbruck, Tyrol, Austria, 6020
      • Medizinische Universität Innsbruck
• Belgium
  • Brussels
    • Bruxelles, Brussels, Belgium, 1070
      • Hôpital Erasme
    • Laeken, Brussels, Belgium, 1020
      • Centre Hospitalier Universitaire Brugmann - Site Victor Horta
  • Flemish Brabant
    • Leuven, Flemish Brabant, Belgium, 3000
      • Universitair Ziekenhuis Leuven - Campus Gasthuisberg
  • Oost-Vlaanderen
    • Gent, Oost-Vlaanderen, Belgium, 9000
      • Universitair Ziekenhuis Gent
• Canada
  • Brampton, Canada, L6R 3J7
    • William Osler Health System - Brampton Civic Hospital
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • University Of Calgary
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 3A7
      • Queen Elizabeth II Health Sciences Centre - Victoria General
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • St. Joseph's Healthcare Hamilton - Charlton Campus
    • London, Ontario, Canada, N6A 2C2
      • Centricity Research (LMC Manna Research) - London
    • North Bay, Ontario, Canada, P1B 2H3
      • Office Of Stephane M. Gauthier
    • Toronto, Ontario, Canada, M6H 3M1
      • Toronto Liver Center
  • Quebec
    • Montréal, Quebec, Canada, H2X 3J4
      • Centre Hospitalier de l'Universite de Montreal (CHUM)
• Czechia
  • Hradec Králové, Czechia, 500 12
    • Hepato-Gastroenterologie HK
  • Prague
    • Praha, Prague, Czechia, 169 02
      • Ustredni vojenska nemocnice Praha
• France
  • Lille, France, 59037
    • Hopital Claude Huriez
  • Marseille, France, 13008
    • Hôpital Saint Joseph Marseille
  • Nice, France, 06202
    • Hôpital l'Archet
  • Paris, France, 75012
    • Hôpital Saint-Antoine
  • Hauts-de-France
    • Lille, Hauts-de-France, France, 59037
      • Hopital Claude Huriez
  • Ile-de-France
    • Créteil, Ile-de-France, France, 94000
      • Hôpitaux Universitaires Henri Mondor
  • Isère
    • Grenoble, Isère, France, 38043
      • Centre Hospitalier Universitaire Grenoble Alpes
  • Limousin
    • Limoges, Limousin, France, 87042
      • Hôpital Dupuytren
  • Lorraine
    • Vandœuvre-lès-Nancy, Lorraine, France, 54511
      • Hopitaux de Brabois
  • Occitanie
    • Toulouse, Occitanie, France, 31059
      • Hôpital Rangueil
    • Toulouse, Occitanie, France, 31076
      • Clinique Pasteur - Toulouse
  • Pays De La Loire
    • Angers, Pays De La Loire, France, 49 933
      • Centre Hosptitalier Universitaire d'Angers
  • Picardie
    • Amiens, Picardie, France, 80054
      • Centre Hospitalier Universitaire Amiens-Picardie - Site Sud
  • Rhone-alpes
    • Lyon, Rhone-alpes, France, 69317
      • Hôpital de la Croix Rousse
• Germany
  • Homburg, Germany, 66421
    • Universitätsklinikum des Saarlandes
  • Bayern
    • Munich, Bayern, Germany, 81675
      • Klinikum rechts der Isar der Technischen Universität München
  • Hessen
    • Frankfurt, Hessen, Germany, 60590
      • Universitätsklinikum Frankfurt
    • Wiesbaden, Hessen, Germany, 65189
      • St. Josefs-Hospital Wiesbaden
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30625
      • Medizinische Hochschule Hannover
  • Sachsen
    • Leipzig, Sachsen, Germany, 04103
      • EUGASTRO
• Greece
  • Heraklion, Greece, 71110
    • University General Hospital of Heraklion (PAGNI)
  • Larissa, Greece, 41110
    • University General Hospital of Larissa
• Hungary
  • Budapest, Hungary, 1082
    • Semmelweis Egyetem - I. Sz. Sebészeti és Intervenciós Gasztroenterológiai Klinika
• Israel
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus
  • Jerusalem, Israel, 9112001
    • Hadassah University Hospital Ein Kerem
  • Tel Aviv, Israel, 64239
    • Tel Aviv Sourasky Medical Center
  • Haifa District
    • Haifa, Haifa District, Israel, 3436212
      • Carmel Medical Center
  • Northern District
    • Nahariya, Northern District, Israel, 22100
      • Western Galilee Hospital-Nahariya
  • Southern District
    • Be'er Sheva, Southern District, Israel, 84101
      • Soroka Medical Center
  • Tel Aviv
    • Petah Tikva, Tel Aviv, Israel, 4941492
      • Rabin Medical Center - Beilinson Hospital
• Italy
  • Ancona, Italy, 60020
    • Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona
  • Messina, Italy, 98124
    • Azienda Ospedaliera Universitaria Policlinico Gaetano Martino
  • Milano, Italy, 20122
    • Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
  • Napoli, Italy, 80131
    • Università degli Studi di Napoli Federico II
  • Novara, Italy, 28100
    • Azienda Ospedaliero-Universitaria Maggiore della Carità di Novara
  • Milan
    • Rozzano, Milan, Italy, 20089
      • Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Istituto Clinico Humanitas
  • Milano
    • Milan, Milano, Italy, 20123
      • Ospedale San Giuseppe
  • Monza And Brianza
    • Monza, Monza And Brianza, Italy, 20900
      • Azienda Socio Sanitaria Territoriale Monza - Ospedale San Gerardo
• New Zealand
  • Dunedin, New Zealand, 9016
    • Dunedin Hospital
  • Hamilton, New Zealand, 3240
    • Waikato Hospital
  • Auckland
    • Grafton, Auckland, New Zealand, 1023
      • Auckland City Hospital
  • Wellington
    • Crofton Downs, Wellington, New Zealand, 6021
      • Wellington Regional Hospital
• Poland
  • Bytom, Poland, 41-902
    • Szpital Specjalistyczny nr 1 w Bytomiu
  • Myslowice, Poland, 41-400
    • ID Clinic
  • Wrocław, Poland, 51-162
    • Centrum Badań Klinicznych Piotr Napora Lekarze Sp. p.
• Spain
  • Alicante, Spain, 03010
    • Hospital General Universitari d'Alicante
  • Almería, Spain, 04009
    • Complejo Hospitalario Torrecárdenas
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona
  • Barcelona, Spain, 08003
    • Hospital del Mar - Parc de Salut Mar
  • Córdoba, Spain, 14004
    • Hospital Universitario Reina Sofia
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28006
    • Hospital Universitario de La Princesa
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Maranon
  • Málaga, Spain, 29010
    • Hospital Universitario Virgen de la Victoria
  • Santiago, Spain, 15706
    • Hospital Clínico Universitario de Santiago
  • Sevilla, Spain, 41011
    • Hospital Universitario Virgen del Rocío
  • València, Spain, 46014
    • Consorci Hospital General Universitari de València
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Germans Trias i Pujol
    • Sabadell, Barcelona, Spain, 08208
      • Hospital de Sabadell
  • Santa Cruz De Tenerife
    • La Laguna, Santa Cruz De Tenerife, Spain, 38320
      • Hospital Universitario de Canarias
• Sweden
  • Uppsala, Sweden, 751 85
    • Akademiska Sjukhuset - Uppsala
• Switzerland
  • Sankt Gallen, Switzerland, 9007
    • Kantonsspital Sankt Gallen
  • Ticino
    • Lugano, Ticino, Switzerland, 6900
      • Fondazione Epatocentro Ticino
• United Kingdom
  • England
    • Gloucester, England, United Kingdom, GL1 3NN
      • Gloucestershire Hospitals NHS Foundation Trust
    • London, England, United Kingdom, SE5 9RS
      • King's College Hospital NHS Foundation Trust
    • Newcastle upon Tyne, England, United Kingdom, NE7 7DN
      • The Newcastle Upon Tyne Hospitals NHS Foundation Trust
    • Nottingham, England, United Kingdom, NG7 2UH
      • Nottingham University Hospitals NHS Trust
    • Sheffield, England, United Kingdom, S10 2JF
      • Sheffield Teaching Hospitals NHS Foundation Trust
    • Southampton, England, United Kingdom, SO16 6YD
      • University Hospital Southampton NHS Foundation Trust
  • Scotland
    • Glasgow, Scotland, United Kingdom, G4 0SF
      • NHS Greater Glasgow and Clyde
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • UA Thomas D. Boyer Liver Institute
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Pasadena, California, United States, 91105
      • California Liver Research Institute
    • Sacramento, California, United States, 95817
      • University of California Davis Medical Center
  • Florida
    • Inverness, Florida, United States, 34452
      • Gastroenterology Associates - Crystal River
    • Miami, Florida, United States, 33136
      • University of Miami Leonard M. Miller School of Medicine
    • Orlando, Florida, United States, 32804
      • AdventHealth Transplant Institute
    • Orlando, Florida, United States, 32825
      • Advanced Research Institute, Inc.
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital
  • Illinois
    • Evanston, Illinois, United States, 60611
      • Northwestern University
    • Springfield, Illinois, United States, 62794-9248
      • Springfield Clinic
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Kansas Medical Clinic - Gastroenterology
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • A. Alfred Taubman Health Care Center
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • Summit - Southern Therapy and Advanced Research
  • New York
    • Manhasset, New York, United States, 11030
      • Northwell Health
    • New York, New York, United States, 10029
      • Icahn School Of Medicine At Mount Sinai
    • New York, New York, United States, 10016
      • New York University Hepatology Associates
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Baptist Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45267-0595
      • University of Cincinnati
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19141
      • Einstein Medical Center
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Rapid City Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Digestive Disease Center
  • Texas
    • Houston, Texas, United States, 77099
      • Pioneer Research Solutions
    • Houston, Texas, United States, 77030
      • Liver Specialists of Texas
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Hospital
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert and Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male or female participant aged ≥18 years, inclusive at the time of informed consent.
• Willing and able to give written informed consent and to comply with the requirements of the study.

• Definite or probable PBC diagnosis as demonstrated by the presence of ≥2 of the following 3 diagnostic factors:

  • Documented history of elevated ALP levels ≥1.67×ULN of the local reference range.
  • Documented history of positive antimitochondrial antibodies (AMA) titer or positive PBC-specific antibodies (anti-GP210 or anti-SP100 or antibodies against the major M2 components [PDC-E2, 2-oxo-glutaric acid dehydrogenase complex]).
  • Historical liver biopsy consistent with PBC.
• Serum ALP ≥1.67×ULN at Screening.
• Liver stiffness measured by transient elastography (FibroScan®) of ≥8.8 kilopascals (kPa) and an interquartile range over median ratio (IQR/med) of ≤30% at Screening, are taken with the results expressed in kilopascals).
• Ursodeoxycholic acid (UDCA) prescriptional dose use for the past 6 months (at a stable dose for >3 months prior to Screening) OR intolerant to UDCA (last dose of UDCA >3 months prior to Screening). Intolerance to UDCA is defined as participants unable to tolerate the full-labelled dose of UDCA in PBC (13-15 mg/kg) due to frequently reported gastrointestinal symptoms such as diarrhea and abdominal pain.
• For participants receiving obeticholic acid (OCA), fenofibrate, or bezafibrate treatment for at least 6 months and stable dose for >3 months prior to Screening.
• For participants intolerant to OCA, OCA must have been discontinued >3 months prior to Screening.
• For participants previously treated with bezafibrate or fenofibrate, and these agents were discontinued prior to screening, they must have been discontinued >3 months prior to Screening.

• Female participants of childbearing potential must use a highly effective method of contraception to prevent pregnancy for ≥4 weeks before Randomization and must agree to continue strict contraception up to 90 days after the last dose of investigational medicinal product (IMP).

  • For the purposes of this trial, women of childbearing potential are defined as "Fertile, following menarche and until becoming postmenopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy."
  • Postmenopausal state is defined as no menses for 12 months without an alternative medical cause. In female participants who are not using hormonal contraception or hormonal replacement therapy but with suspected menopause and less than 12 months of amenorrhea, a high follicle stimulating hormone (FSH) level in the postmenopausal range will be required at Screening to confirm a postmenopausal state. Confirmation with more than one FSH measurement is required.

  • Highly effective contraception is defined as methods that can achieve a failure rate of less than 1% per year when used consistently and correctly. These methods are:

    • Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal)
    • Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable)
    • Intrauterine device
    • Intrauterine hormone-releasing system
    • Bilateral tubal occlusion
    • Vasectomized partner
    • Sexual abstinence (refraining from heterosexual intercourse during the entire period of risk associate with the study treatments). The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant. Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method are not acceptable methods of contraception. Female condom and male condom should not be used together.
• Female participants of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Baseline/Randomization before dosing.
• Male participants with female partners of childbearing potential must be willing to use a condom and require their partner to use a highly effective contraceptive method. This requirement begins at the time of informed consent and ends 90 days after receiving the last dose of IMP.
• Male participants must be willing not to donate sperm, and female study participants must be willing not to donate eggs, from Baseline until 90 days after the last dose of IMP.

Exclusion Criteria:

• A positive pregnancy test or breastfeeding for female participants.
• Any historical or current hepatic decompensation event defined as variceal/portal hypertension bleed and/or hepatic encephalopathy, spontaneous bacterial peritonitis, ascites requiring treatment, or liver transplantation list inclusion.
• History of liver transplantation, current placement on a liver transplant list or current model for end stage liver disease (MELD) score of ≥12 unless the participant is on anticoagulant therapy, or a Child-Pugh Score of ≥6.
• Cirrhosis with complications, including history or presence of hepatocellular carcinoma.
• Total bilirubin >2×ULN. In case of total bilirubin elevation >ULN the Screening serum albumin must be within the reference range.
• Plasma alanine aminotransferase (ALT) >3×ULN and/or aspartate aminotransferase (AST) >3×ULN.
• International normalized ratio (INR) >1.2 unless participant is on anticoagulant therapy. One repeat blood sampling (with analysis by the central laboratory) can be performed at the discretion of the Investigator at Screening Visit 2 for participants who meet this exclusion criterion at Screening Visit 1. If this exclusion criterion is not met at Screening Visit 2, the participant may be eligible for the study.
• Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m^2, as calculated by the central laboratory using the chronic kidney disease-epidemiology collaboration (CKD- EPI) equation.
• Thyroid-stimulating hormone >ULN at Screening. One repeat blood sampling (with analysis by the central laboratory) can be performed at the discretion of the Investigator at Screening Visit 2 for participants who meet this exclusion criterion at Screening Visit 1. If this exclusion criterion is not met at Screening Visit 2, the participant may be eligible for the study.
• Competing etiology for liver disease (eg, hepatitis C [unless effectively cured of hepatitis C, with a sustained virologic response for at least 6 months prior to Screening], active hepatitis B [HBsAg positive], nonalcoholic steatohepatitis [NASH], alcoholic liver disease, autoimmune hepatitis, autoimmune hepatitis-PBC overlap syndrome, primary sclerosing cholangitis, Gilbert's Syndrome).
• Medical conditions that could cause nonhepatic increases in ALP (eg, Paget's disease).
• Known history of human immunodeficiency virus (HIV) infection.
• Surgery (eg, stomach bypass) or medical condition that might significantly affect absorption of medicines (as judged by the Investigator).
• Positive urine drug screen (if not due to prescriptional use of a concomitant medication, as confirmed by the Investigator) at Screening. Participants on stable methadone or buprenorphine maintenance treatment for at least 6 months prior to Screening Visit 1 may be included in the study. Medicinal cannabis and cannabidiol products are not exclusionary and may be allowed if the prescription and diagnosis are reviewed and approved by the Investigator.
• Participants receiving prohibited medications within 3 months of Screening Visit 1.
• Treatment with any investigational agent within 12 weeks of Screening Visit 1 or 5 half-lives of the IMP (if known) (whichever is longer) or current enrollment in an interventional clinical trial.
• Evidence of any of the following cardiac conduction abnormalities: A QTc Fridericia interval >450 milliseconds for males or >470 milliseconds for females, as calculated by the central reader. Participants with a second- or third-degree atrioventricular block are to be excluded.

• History of a malignancy within 5 years of Screening with the following exceptions:

  • Adequately treated carcinoma in situ of the cervix.
  • Adequately treated basal or squamous cell cancer or other localized nonmelanoma skin cancer.
• The occurrence of any acute infection requiring systemic antibiotic therapy within the 2 weeks prior to Screening Visit 1.
• A history of bone marrow disorder including aplastic anemia, or any current marked anemia defined as hemoglobin <10.0 g/dL.
• Prior treatment with setanaxib or participation in a previous setanaxib clinical trial.
• Unstable cardiovascular disease.
• Presence of any laboratory abnormality or condition that, in the opinion of the Investigator, could interfere with or compromise a participant's treatment, assessment, or compliance with the protocol and/or study procedures.
• Any other condition which, in the opinion of the Investigator, constitutes a risk or contraindication for the participation of the participant in the study, or that could interfere with the study objectives, conduct, or evaluation.
• Hypersensitivity or intolerance to setanaxib or to any of its excipients or placebo compounds.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Setanaxib 1200 mg/day; Participants will be administered setanaxib at a dose of 1200 mg/day for the 24-week double-blind treatment period.	Drug: Setanaxib; Oral tablets, 400mg per tablet
Experimental: Setanaxib 1600 mg/day; Participants will be administered setanaxib at a dose of 1600 mg/day for the 24-week double-blind treatment period.	Drug: Setanaxib; Oral tablets, 400mg per tablet
Placebo Comparator: Placebo; Participants will be administered a placebo for the 24-week double-blind treatment period.	Drug: Placebo; Oral tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in ALP at Week 24 Compared to Baseline	Change in ALP at Week 24 Compared to Baseline, ratio of week 24 value to baseline value.	Baseline (Day 1) and Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Fatigue at Week 24 Compared to Baseline, as Assessed by the PROMIS Short Form-Fatigue 7b Daily	The Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form 7b measures the severity of fatigue since waking. There are 7 questions, each scored between 1 and 5, with a total score between 7 to 35. A higher score indicates worse fatigue. This raw score is converted to a T score (a standardized score with a mean of 50 and a SD of 10).	Baseline (Day 1) and Week 24
Change in Fatigue at Week 24 Compared to Baseline, as Assessed by the Patient's Global Impression of Severity (PGIS) Fatigue	The Patient's Global Impression of Severity (PGIS)-Fatigue is a global index where subjects are asked to rate the severity of fatigue on a 5-point scale within the past 7 days, with choices of 1=None, 2=Mild, 3=Moderate, 4=Severe and 5=Very Severe. Higher scores indicate a worse assessment for fatigue.	Baseline (Day 1) and Week 24
Change in Fatigue at Week 24 Compared to Baseline, as Assessed by the Patient's Global Impression of Change (PGIC) Fatigue	The Patient's Global Impression of Change (PGIC)-Fatigue is a 7-point scale reflecting a subject's rating of overall improvement where subjects are asked to rate their overall improvement with fatigue with 1=Very much improved, 2=Much improved, 3=Minimally improved, 4=No change, 5=Worse, 6=Much worse, 7=Very much worse. Higher scores indicate a worse outcome for change in fatigue.	Week 24
Change in Fatigue at Week 24 Compared to Baseline, as Assessed by the PBC-40 Questionnaire (PBC 40) Fatigue Domain	PBC-40 fatigue domain includes 11 item questions, items scores range from 1 to 5. The individual item scores are summed to obtain a total domain score (Range for fatigue domain: 11 to 55), high scores represent high impact and low scores indicate low impact of PBC on the quality of life.	Baseline (Day 1) and Week 24
Change in Liver Stiffness at Week 24 Compared to Screening	Change in liver stiffness at Week 24 compared to Screening, as assessed by transient elastography (FibroScan®)	Screening (Day -28) and Week 24
Change in Pruritus at Week 24 Compared to Baseline, as Assessed by the Worst Itch Numerical Rating Scale (WI-NRS)	WI-NRS is a daily patient-reported measure of itch intensity using an 11-point scale where 0=no itch and 10=worst itching imaginable. The WI-NRS score is calculated by averaging the daily WI-NRS scores before the visit date (inclusive). Higher scores indicate worse functioning for pruritus on the WI-NRS.	Baseline (Day 1) and Week 24
Change in Pruritus at Week 24 Compared to Baseline, as Assessed by the PBC-40 Itch Domain	Pruritus was assessed by answering 3 questions on the PBC-40 Itch domain from 1 to 5, which was also summed to obtain a total domain score (range 3 to 15). A high score represents a high impact, and a low score indicates low impact of pruritus on the quality of life.	Baseline (Day 1) and Week 24
Change in Pruritus at Week 24 Compared to Baseline, as Assessed by the PGIS Pruritus	PGIS-Pruritus is a global index where subjects are asked to rate the severity of pruritus on a 5-point scale within the past 7 days, with choices of 1=None, 2=Mild, 3=Moderate, 4=Severe and 5=Very Severe. Higher scores indicate a worse assessment for pruritus.	Baseline (Day 1) and Week 24
Change in Pruritus at Week 24 Compared to Baseline, as Assessed by the PGIC Pruritus	The PGIC-Pruritus is a 7-point scale reflecting a subject's rating of overall improvement where subjects are asked to rate their overall improvement with fatigue with 1=Very much improved, 2=Much improved, 3=Minimally improved, 4=No change, 5=Worse, 6=Much worse, 7=Very much worse. Higher scores indicate a worse outcome for change in pruritus.	Week 24
Changes in Markers of Cholestasis at Week 24	Changes in markers of cholestasis as assessed by proportion of patients at Week 24 with: ALP reduction to <1.67×ULN and total bilirubin ≤1×ULN and a ≥15% or ≥30% or ≥40% or ≥70% ALP reduction from Baseline, respectively; ALP reduction to <1.5×ULN and total bilirubin ≤1×ULN and a ≥40% ALP reduction from Baseline; ALP <1×ULN and total bilirubin ≤1×ULN; Total bilirubin <0.6×ULN	Baseline (Day 1) and Week 24
Change in ALP at Week 24 Compared to Baseline, Where Setanaxib Doses Are Combined	Change in ALP at Week 24 Compared to Baseline, ratio of week 24 value to baseline value. Setanaxib doses are combined and the change from baseline is estimated using a mixed model-repeated measures approach with fixed factors for treatment, visit, log(baseline), treatment*visit, and log(baseline)*visit, subject is included as a random effect. The variance-covariance matrix is therefore not the same as in the three arm analysis, which causes treatment effects estimated in the placebo to group differ from those estimated in the analysis with three treatment arms.	Baseline (Day 1) and Week 24
Change in Fatigue at Week 24 Compared to Baseline, as Assessed by the PROMIS Short Form-Fatigue 7b Daily, Where Setanaxib Doses Are Combined	The Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form 7b measures the severity of fatigue since waking. There are 7 questions, each scored between 1 and 5, with a total score between 7 to 35. A higher score indicates worse fatigue. This raw score is converted to a T score (a standardized score with a mean of 50 and a SD of 10). Setanaxib doses are combined and the change from baseline is estimated using a mixed model-repeated measures approach with fixed factors for treatment, visit, log(baseline), treatment*visit, and log(baseline)*visit, subject is included as a random effect. The variance-covariance matrix is therefore not the same as in the three arm analysis, which causes treatment effects estimated in the placebo to group differ from those estimated in the analysis with three treatment arms.	Baseline (Day 1) and Week 24
Change in Fatigue at Week 24 Compared to Baseline, as Assessed by the PBC-40 Questionnaire (PBC 40) Fatigue Domain, Where Setanaxib Doses Are Combined	PBC-40 fatigue domain includes 11 item questions, items scores range from 1 to 5. The individual item scores are summed to obtain a total domain score (Range for fatigue domain: 11 to 55), high scores represent high impact and low scores indicate low impact of PBC on the quality of life. Setanaxib doses are combined and the change from baseline is estimated using a mixed model-repeated measures approach with fixed factors for treatment, visit, log(baseline), treatment*visit, and log(baseline)*visit, subject is included as a random effect. The variance-covariance matrix is therefore not the same as in the three arm analysis, which causes treatment effects estimated in the placebo to group differ from those estimated in the analysis with three treatment arms.	Baseline (Day 1) and Week 24
Change in Liver Stiffness at Week 24 Compared to Screening, Where Setanaxib Doses Are Combined	Change in liver stiffness at Week 24 compared to Screening, as assessed by transient elastography (FibroScan®). Setanaxib doses are combined and the change from baseline is estimated using a mixed model-repeated measures approach with fixed factors for treatment, visit, log(baseline), treatment*visit, and log(baseline)*visit, subject is included as a random effect. The variance-covariance matrix is therefore not the same as in the three arm analysis, which causes treatment effects estimated in the placebo to group differ from those estimated in the analysis with three treatment arms.	Screening (Day -28) and Week 24

Collaborators and Investigators

• Sponsor: Calliditas Therapeutics Suisse SA

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2022
• Primary Completion (Actual): May 31, 2024
• Study Completion (Actual): July 2, 2024

Study Registration Dates

• First Submitted: August 10, 2021
• First Submitted That Met QC Criteria: August 18, 2021
• First Posted (Actual): August 20, 2021

Study Record Updates

• Last Update Posted (Actual): April 24, 2025
• Last Update Submitted That Met QC Criteria: April 7, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Primary Biliary Cholangitis; Setanaxib; Elevated Liver Stiffness
• Additional Relevant MeSH Terms: Pathologic Processes; Digestive System Diseases; Biliary Tract Diseases; Liver Diseases; Bile Duct Diseases; Fibrosis; Cholestasis, Intrahepatic; Cholestasis; Liver Cirrhosis; Cholangitis; Liver Cirrhosis, Biliary
• Other Study ID Numbers: GSN000350; 2021-001810-13 (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