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

NCT05014672 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: GSN0003502021-001810-13
• Study Type: interventional
• Target: 76
• Locations: 17 countries
• Sites: 124

Brief Summary

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).

Conditions

Primary Biliary Cholangitis; Liver Stiffness

Keywords

Setanaxib; Primary Biliary Cholangitis; Elevated Liver Stiffness

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (14)

• Change in Fatigue at Week 24 Compared to Baseline, as Assessed by the PROMIS Short Form-Fatigue 7b Daily

  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

  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

  Week 24

• Change in Fatigue at Week 24 Compared to Baseline, as Assessed by the PBC-40 Questionnaire (PBC 40) Fatigue Domain

  Baseline (Day 1) and Week 24

• Change in Liver Stiffness at Week 24 Compared to Screening

  Screening (Day -28) and Week 24

Study Arms (3)

Setanaxib 1200 mg/day

EXPERIMENTAL

Participants will be administered setanaxib at a dose of 1200 mg/day for the 24-week double-blind treatment period.

Drug: Setanaxib

Setanaxib 1600 mg/day

EXPERIMENTAL

Participants will be administered setanaxib at a dose of 1600 mg/day for the 24-week double-blind treatment period.

Drug: Setanaxib

Placebo

PLACEBO COMPARATOR

Participants will be administered a placebo for the 24-week double-blind treatment period.

Drug: Placebo

Interventions

Setanaxib DRUG

Oral tablets, 400mg per tablet

Setanaxib 1200 mg/day; Setanaxib 1600 mg/day

Placebo DRUG

Oral tablets

Placebo

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• A positive pregnancy test or breastfeeding for female participants.
• 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.
• 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.
• 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).
• 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.

Sponsors & Collaborators

• Calliditas Therapeutics Suisse SA: lead

Study Sites (128)

UA Thomas D. Boyer Liver Institute

Tucson, Arizona, 85724, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

California Liver Research Institute

Pasadena, California, 91105, United States

Location

University of California Davis Medical Center

Sacramento, California, 95817, United States

Location

Gastroenterology Associates - Crystal River

Inverness, Florida, 34452, United States

Location

University of Miami Leonard M. Miller School of Medicine

Miami, Florida, 33136, United States

Location

AdventHealth Transplant Institute

Orlando, Florida, 32804, United States

Location

Advanced Research Institute, Inc.

Orlando, Florida, 32825, United States

Location

Tampa General Hospital

Tampa, Florida, 33606, United States

Location

Northwestern University

Evanston, Illinois, 60611, United States

Location

Springfield Clinic

Springfield, Illinois, 62794-9248, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Kansas Medical Clinic - Gastroenterology

Topeka, Kansas, 66606, United States

Location

Tulane Medical Center

New Orleans, Louisiana, 70112, United States

Location

A. Alfred Taubman Health Care Center

Ann Arbor, Michigan, 48109, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Summit - Southern Therapy and Advanced Research

Jackson, Mississippi, 39216, United States

Location

Northwell Health

Manhasset, New York, 11030, United States

Location

New York University Hepatology Associates

New York, New York, 10016, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267-0595, United States

Location

Einstein Medical Center

Philadelphia, Pennsylvania, 19141, United States

Location

Rapid City Medical Center

Rapid City, South Dakota, 57701, United States

Location

Vanderbilt Digestive Disease Center

Nashville, Tennessee, 37232, United States

Location

Liver Specialists of Texas

Houston, Texas, 77030, United States

Location

Pioneer Research Solutions

Houston, Texas, 77099, United States

Location

University of Utah Hospital

Salt Lake City, Utah, 84132, United States

Location

Froedtert and Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

John Hunter Hospital

New Lambton Heights, New South Wales, 2305, Australia

Location

Mater Misericordiae - Hospital Brisbane

South Brisbane, Queensland, 4101, Australia

Location

Flinders Medical Centre

Bedford Park, South Australia, 5042, Australia

Location

Eastern Health - Australia

Box Hill, Victoria, 3128, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

Fiona Stanley Hospital

Murdoch, Western Australia, 6150, Australia

Location

Nepean Hospital

Kingswood, 2747, Australia

Location

Liverpool Hospital

Liverpool, 2170, Australia

Location

The Alfred Hospital

Melbourne, 3004, Australia

Location

Universitaetsklinikum Graz - Universitätsklinik für Innere Medizin

Graz, Styria, 8036, Austria

Location

Medizinische Universität Innsbruck

Innsbruck, Tyrol, 6020, Austria

Location

Ordensklinikum Linz GmbH Barmherzige Schwestern

Linz, Upper Austria, 4010, Austria

Location

Klinikum Wels-Grieskirchen

Wels, Upper Austria, 4600, Austria

Location

Hôpital Erasme

Brussels, Brussels Capital, 1070, Belgium

Location

Centre Hospitalier Universitaire Brugmann - Site Victor Horta

Laken, Brussels Capital, 1020, Belgium

Location

Universitair Ziekenhuis Leuven - Campus Gasthuisberg

Leuven, Flemish Brabant, 3000, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, Oost-Vlaanderen, 9000, Belgium

Location

University of Calgary

Calgary, Alberta, T2N 4Z6, Canada

Location

Queen Elizabeth II Health Sciences Centre - Victoria General

Halifax, Nova Scotia, B3H 3A7, Canada

Location

St. Joseph's Healthcare Hamilton - Charlton Campus

Hamilton, Ontario, L8N 4A6, Canada

Location

Centricity Research (LMC Manna Research) - London

London, Ontario, N6A 2C2, Canada

Location

Office Of Stephane M. Gauthier

North Bay, Ontario, P1B 2H3, Canada

Location

Toronto Liver Center

Toronto, Ontario, M6H 3M1, Canada

Location

Centre Hospitalier de l'Université de Montréal (CHUM)

Montreal, Quebec, H2X 3J4, Canada

Location

William Osler Health System - Brampton Civic Hospital

Brampton, L6R 3J7, Canada

Location

Ústřední Vojenská Nemocnice Praha

Prague, Prague, 169 02, Czechia

Location

Hepato-Gastroenterologie HK

Hradec Králové, 500 12, Czechia

Location

Hôpital de la Croix Rousse

Lyon, Auvergne-Rhône-Alpes, 69317, France

Location

Hôpital Claude Huriez

Lille, Hauts-de-France, 59037, France

Location

Centre Hospitalier Universitaire Grenoble Alpes

Grenoble, Isère, 38043, France

Location

Hopital Dupuytren

Limoges, Limousin, 87042, France

Location

Hôpitaux de Brabois

Vandœuvre-lès-Nancy, Lorraine, 54511, France

Location

Hôpital Rangueil

Toulouse, Occitanie, 31059, France

Location

Clinique Pasteur - Toulouse

Toulouse, Occitanie, 31076, France

Location

Centre Hosptitalier Universitaire d'Angers

Angers, Pays de la Loire Region, 49 933, France

Location

Centre Hospitalier Universitaire Amiens-Picardie - Site Sud

Amiens, Picardie, 80054, France

Location

Hôpital Claude Huriez

Lille, 59037, France

Location

Hôpital Saint Joseph Marseille

Marseille, 13008, France

Location

Hôpital l'Archet

Nice, 06202, France

Location

Hôpital Saint-Antoine

Paris, 75012, France

Location

Hôpitaux Universitaires Henri Mondor

Créteil, Île-de-France Region, 94000, France

Location

Klinikum rechts der Isar der Technischen Universität München

Munich, Bavaria, 81675, Germany

Location

Universitätsklinikum Frankfurt

Frankfurt am Main, Hesse, 60590, Germany

Location

St. Josefs-Hospital Wiesbaden

Wiesbaden, Hesse, 65189, Germany

Location

Medizinische Hochschule Hannover

Hanover, Lower Saxony, 30625, Germany

Location

Eugastro

Leipzig, Saxony, 04103, Germany

Location

Universitätsklinikum des Saarlandes

Homburg, 66421, Germany

Location

University General Hospital of Heraklion (PAGNI)

Heraklion, 71110, Greece

Location

University General Hospital of Larissa

Larissa, 41110, Greece

Location

Semmelweis Egyetem - I. Sz. Sebészeti és Intervenciós Gasztroenterológiai Klinika

Budapest, 1082, Hungary

Location

Carmel Medical Center

Haifa, Haifa District, 3436212, Israel

Location

Western Galilee Hospital-Nahariya

Nahariya, Northern District, 22100, Israel

Location

Soroka Medical Center

Beersheba, Southern District, 84101, Israel

Location

Rabin Medical Center - Beilinson Hospital

Petah Tikva, Tel Aviv, 4941492, Israel

Location

Rambam Health Care Campus

Haifa, 3109601, Israel

Location

Hadassah University Hospital Ein Kerem

Jerusalem, 9112001, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

Ospedale San Giuseppe

Milan, Milano, 20123, Italy

Location

Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Istituto Clinico Humanitas

Rozzano, Milan, 20089, Italy

Location

Azienda Socio Sanitaria Territoriale Monza - Ospedale San Gerardo

Monza, Monza and Brianza, 20900, Italy

Location

Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona

Ancona, 60020, Italy

Location

Azienda Ospedaliera Universitaria Policlinico Gaetano Martino

Messina, 98124, Italy

Location

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

Università degli Studi di Napoli Federico II

Napoli, 80131, Italy

Location

Azienda Ospedaliero-Universitaria Maggiore della Carità di Novara

Novara, 28100, Italy

Location

Auckland City Hospital

Grafton, Auckland, 1023, New Zealand

Location

Wellington Regional Hospital

Crofton Downs, Wellington Region, 6021, New Zealand

Location

Dunedin Hospital

Dunedin, 9016, New Zealand

Location

Waikato Hospital

Hamilton, 3240, New Zealand

Location

Szpital Specjalistyczny Nr 1 w Bytomiu

Bytom, 41-902, Poland

Location

ID Clinic

Mysłowice, 41-400, Poland

Location

Centrum Badań Klinicznych Piotr Napora Lekarze Sp. p.

Wroclaw, 51-162, Poland

Location

Hospital Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Hospital de Sabadell

Sabadell, Barcelona, 08208, Spain

Location

Hospital Universitario de Canarias

San Cristóbal de La Laguna, Santa Cruz De Tenerife, 38320, Spain

Location

Hospital General Universitari d'Alicante

Alicante, 03010, Spain

Location

Complejo Hospitalario Torrecárdenas

Almería, 04009, Spain

Location

Hospital del Mar - Parc de Salut Mar

Barcelona, 08003, Spain

Location

Hospital Clínic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario Reina Sofía

Córdoba, 14004, Spain

Location

Hospital Universitario de La Princesa

Madrid, 28006, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, 28007, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

Hospital Clínico Universitario de Santiago

Santiago, 15706, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41011, Spain

Location

Consorci Hospital General Universitari de València

Valencia, 46014, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

Akademiska Sjukhuset - Uppsala

Uppsala, 751 85, Sweden

Location

Fondazione Epatocentro Ticino

Lugano, Canton Ticino, 6900, Switzerland

Location

Kantonsspital Sankt Gallen

Sankt Gallen, 9007, Switzerland

Location

Gloucestershire Hospitals NHS Foundation Trust

Gloucester, England, GL1 3NN, United Kingdom

Location

King's College Hospital NHS Foundation Trust

London, England, SE5 9RS, United Kingdom

Location

The Newcastle Upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, England, NE7 7DN, United Kingdom

Location

Nottingham University Hospitals NHS Trust

Nottingham, England, NG7 2UH, United Kingdom

Location

Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield, England, S10 2JF, United Kingdom

Location

University Hospital Southampton NHS Foundation Trust

Southampton, England, SO16 6YD, United Kingdom

Location

NHS Greater Glasgow and Clyde

Glasgow, Scotland, G4 0SF, United Kingdom

Location

MeSH Terms

Conditions

Liver Cirrhosis, Biliary

Interventions

setanaxib

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Head of Clinical Operations
• Organization: Calliditas Therapeutics AB

info@calliditas.com

+4684113005

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Placebo-controlled 1:1:1 in double blind treatment period.

Study Record Dates

• First Submitted: August 10, 2021
• First Posted: August 20, 2021
• Study Start: February 14, 2022
• Primary Completion: May 31, 2024
• Study Completion: July 2, 2024
• Last Updated: April 24, 2025
• Results First Posted: April 24, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (8); CZ (2); DE (6); PL (3); FR (14); HU (1); US (29); BE (4); AU (10); IT (8); NZ (4); IL (7); SE (1); CH (2); GB (7); ES (16); GR (2)