Study to Assess Safety & Efficacy of GKT137831 in Patients With Primary Biliary Cholangitis Receiving Ursodiol.

NCT03226067 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: GSN0003002016-004599-23
• Study Type: interventional
• Target: 111
• Locations: 9 countries
• Sites: 61

Brief Summary

The purpose of this study is to assess the safety and efficacy of GKT13783 in patients with Primary Biliary Cholangitis (PBC) who are taking a stable dose of ursodeoxycholic acid (UDCA) treatment, and have persistently high levels of a liver enzyme called Alkaline Phosphatase (ALP).

Conditions

Primary Biliary Cirrhosis

Outcome Measures

Primary Outcomes (1)

• The Percent Change in Serum GGT.

  Percent change in serum GGT from baseline to Week 24 (serum GGT was measured in U/L)

  Baseline to week 24 (visit 7)

Secondary Outcomes (17)

• Absolute Change in Serum GGT

  From baseline to Weeks 2, 6, 12, 18 and 24

• Percent Change in Serum GGT

  From baseline to Weeks 2, 6, 12, 18 and 24

• Percent Change in Serum ALP

  From baseline to Weeks 2, 6, 12, 18 and 24

• Absolute Change in Serum ALP

  From baseline to Weeks 2, 6, 12, 18 and 24

• Absolute Change in Serum Conjugated Bilirubin.

  From baseline to Weeks 2, 6, 12, 18 and 24

Study Arms (3)

GKT137831 400mg twice daily

EXPERIMENTAL

GKT137831 400mg twice daily Patients will self-administer 4 capsules in the morning and 4 capsules in the evening.

Drug: GKT137831

GKT137831 400mg once daily

EXPERIMENTAL

GKT137831 400mg once daily Patients will self-administer 4 capsules in the morning and 4 capsules in the evening. The capsules in the evening will be placebos.

Drug: GKT137831; Drug: Placebo oral capsule

Placebo Arm

PLACEBO COMPARATOR

Patients will self-administer 4 capsules in the morning and 4 capsules in the evening. All capsules will be placebos.

Drug: Placebo oral capsule

Interventions

GKT137831 DRUG

GKT137831 100mg capsules. To be taken as part of two dose arms which are 400mg twice daily or 400mg once daily.

Also known as: setanaxib

GKT137831 400mg once daily; GKT137831 400mg twice daily

Placebo oral capsule DRUG

Matching capsules.

Also known as: Placebo

GKT137831 400mg once daily; Placebo Arm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged 18 to 80 years, inclusive.
• Willing and able to give written informed consent and to comply with the requirements of the study.
• PBC diagnosis as demonstrated by the presence of ≥ 2 of the following 3 diagnostic factors:
• History of elevated ALP levels (\> ULN) for at least 6 months
• Positive anti-mitochondrial antibody (AMA) titer or if AMA negative or in low titer (\< 1:80) PBC-specific antibodies (anti-GP210 and/or anti-SP100 and/or antibodies against the major M2 components \[PDC-E2, 2-oxo-glutaric acid dehydrogenase complex\])
• Liver biopsy consistent with PBC (based on historic liver biopsy), including non-suppurative, destructive cholangitis affecting mainly the interlobular and septal bile ducts.
• Serum ALP ≥ 1.5 x ULN.
• Serum GGT ≥ 1.5 x ULN.
• UDCA treatment for at least 6 months and stable dose for at least 3 months prior to Visit 1.
• Subjects being treated for pruritus with colestyramine must be on a stable dose of colestyramine for at least 8 weeks prior to baseline/Day 1 (Visit 2). Subjects must be willing and able to take colestyramine at least 2 hours before or after study medication.
• Female subjects 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 for 90 days after last administration of investigational medicinal product (IMP). Male participants with female partners of childbearing potential must be willing to use a condom and require their partner to use an additional form of adequate contraception as approved by the Investigator. This requirement begins at the time of informed consent and ends 90 days after the last administration of IMP. Male study participants must also not donate sperm from baseline until 90 days after the last administration of IMP.

You may not qualify if:

• A positive pregnancy test or breast-feeding for female subjects.
• Any hepatic decompensation, defined as a past or current history of hepatic encephalopathy, gastrointestinal tract bleeding due to esophageal varices, or ascites.
• International normalized ratio (INR) \> 1.2 unless subject is on anticoagulant therapy.
• ALT \> 3 x ULN.
• Total bilirubin \> 1 x ULN.
• Planned or current plasmapheresis or other extra-corporeal treatments (e.g., molecular adsorbent recirculation system (MARS)) for treatment-refractory pruritus.
• History of liver transplantation, current placement on a liver transplant list or current Model for End Stage Liver Disease (MELD) score ≥ 15.
• Cirrhosis with complications, including history or presence of: spontaneous bacterial peritonitis, hepatocellular carcinoma.
• Hepatorenal syndrome (type I or II) or Screening serum creatinine \> ULN.
• Competing etiology for liver disease (e.g., hepatitis C, active hepatitis B, non-alcoholic steatohepatitis (NASH), alcoholic liver disease (ALD), autoimmune hepatitis, primary sclerosing cholangitis, Gilbert's Syndrome).
• Subjects receiving prohibited medications within 3 months of Screening (Visit 1) according to the list (a, b and c) provided in Section 6.6.2.
• Treatment with any investigational agent within 4 weeks of Visit 1 or 5 half-lives of the investigational medicinal product (whichever is longer).
• A history of long QT syndrome.
• Evidence of any of the following cardiac conduction abnormalities during the screening period:
• A QTc Fredericia interval \>450 milliseconds for males and \>470 milliseconds for females.

Sponsors & Collaborators

• Calliditas Therapeutics AB: lead

Study Sites (61)

Mayo Clinic

Phoenix, Arizona, 85054, United States

Location

University California Davis

Sacramento, California, 95817, United States

Location

Ventura Clinical Trials

Ventura, California, 93003, United States

Location

Yale School of Medicine

New Haven, Connecticut, 06520-8019, United States

Location

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Tulane University Medical Center

New Orleans, Louisiana, 70112, United States

Location

Jackson Liver and GI Specialist c/o (STAR) LLC

Jackson, Mississippi, 39216, United States

Location

North Shore University Hospital

Manhasset, New York, 11030, United States

Location

NYU Hepatology Associates

New York, New York, 10016, United States

Location

Mount Sinai Health System

New York, New York, 10029, United States

Location

University of Rochester Medical Centre

Rochester, New York, 14642, United States

Location

Dayton Gastroenterology Inc.

Beavercreek, Ohio, 45440, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

UPMC Center for Liver Diseases

Pittsburgh, Pennsylvania, 15213, United States

Location

Methodist University Hospital

Memphis, Tennessee, 38104, United States

Location

St Lukes Episcopal Hospital

Houston, Texas, 77030, United States

Location

Pinnacle Clinical Research, PLLC

Live Oak, Texas, 78233, United States

Location

Bon Secours Liver Institute of Hampton Roads

Newport News, Virginia, 23602, United States

Location

Bon Secours Liver Institute of Richmond

Richmond, Virginia, 23226, United States

Location

CUB Hôpital Erasme

Brussels, 1070, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

University of Calgary Liver Unit

Calgary, Alberta, T2N4z6, Canada

Location

University of Manitoba

Winnipeg, Manitoba, R3E3P4, Canada

Location

Centre hospitalier de l'Universite de Montreal (CHUM) Centre de Recherche Service d'Hepatologie

Montreal, Quebec, H2X0A9, Canada

Location

McGill University Health Centre (MUHC)

Montreal, Quebec, H4A3J1, Canada

Location

Friedrich-Alexander University Erlangen-Nürnberg

Erlangen, Bavaria, 91054, Germany

Location

Johann Wolfgang Goethe-University

Frankfurt am Main, Hesse, 60590, Germany

Location

Universitatsklinikum Bonn

Bonn, North Rhine-Westphalia, 53105, Germany

Location

Universitätsklinikum Heidelberg

Heidelberg, D-69210, Germany

Location

Universitätsmedizin Mainz

Mainz, D-55131, Germany

Location

General Hospital of Athens "Hippocratio"

Athens, 11527, Greece

Location

Laiko General Hospital

Athens, 11527, Greece

Location

University Hospital of Larissa

Larissa, 41100, Greece

Location

Rambam Health Centre

Haifa, 3109601, Israel

Location

Shaare Zedek Medical Center

Jerusalem, 9103102, Israel

Location

Hadassah Medical Organization

Jerusalem, 91120, Israel

Location

Rabin Medical Centre

Petach-Tiqva, 49100, Israel

Location

Sheba Medical Centre

Ramat Gan, 52621, Israel

Location

Sourasky Tel-Aviv Medical Center

Tel Aviv, 3906, Israel

Location

University of Milan-Bicocca

Monza, Lombardy, 20900, Italy

Location

Università Politecnica delle Marche - Facoltà di Medicina e Chirurgia

Ancona, 60126, Italy

Location

Policlinico of Bologna

Bologna, 40138, Italy

Location

San Giovanni Rotondo Hospital (Puglia)

Foggia, 71013, Italy

Location

University Hospital Padova

Padua, 35128, Italy

Location

Hospital Clinic de Barcelona

Barcelona, 8036, Spain

Location

Hospital Puerta de Hierro-Majadahonda

Madrid, 28222, Spain

Location

University of Alcalá

Madrid, 28223, Spain

Location

Virgen De La Victoria University Hospital

Málaga, 29015, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Cambridge University Hospitals NHS Foundation Trust

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

Location

Plymouth Hospital NHS Trust

Plymouth, Devon, PL6 8DH, United Kingdom

Location

Hull and East Yorkshire Hospitals NHS Trust

Hull, East Yorkshire, HU3 2JZ, United Kingdom

Location

Gloucestershire Royal Hospital

Gloucester, Gloucestershire, GL13NN, United Kingdom

Location

Oxford University Hospitals NHS Foundation Trust

Oxford, Oxfordshire, OX3 9DU, United Kingdom

Location

Tayside Medical Science Centre (TASC)

Dundee, Tayside, DD19SY, United Kingdom

Location

University Hospitals Birmingham NHS Foundation Trust

Birmingham, B152GW, United Kingdom

Location

King's College Hospital NHS Foundation Trust

London, SE5 9RS, United Kingdom

Location

Singleton Hospital

Swansea, SA28PP, United Kingdom

Location

Related Publications (2)

• Invernizzi P, Carbone M, Jones D, Levy C, Little N, Wiesel P, Nevens F; study investigators. Setanaxib, a first-in-class selective NADPH oxidase 1/4 inhibitor for primary biliary cholangitis: A randomized, placebo-controlled, phase 2 trial. Liver Int. 2023 Jul;43(7):1507-1522. doi: 10.1111/liv.15596. Epub 2023 May 15.

  PMID: 37183520 DERIVED

• Jones D, Carbone M, Invernizzi P, Little N, Nevens F, Swain MG, Wiesel P, Levy C. Impact of setanaxib on quality of life outcomes in primary biliary cholangitis in a phase 2 randomized controlled trial. Hepatol Commun. 2023 Feb 20;7(3):e0057. doi: 10.1097/HC9.0000000000000057. eCollection 2023 Mar 1.

  PMID: 36809195 DERIVED

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: Richard Philipson, MD Chief Medical Officer
• Organization: Calliditas Therapeutics

richard.philipson@calliditas.com

Desk: +46 556659-9766

Study Officials

• Philippe Wiesel, MD

  Calliditas Therapeutics AB

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: This is a double-blind study: the Sponsor, subjects, investigator staff, persons performing the assessments and data reviewers and statisticians will remain blinded to the identity of the study treatments.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This will be a double-blind, randomized, placebo-controlled, multicenter, parallel group phase 2 trial. A total of 102 subjects will be randomized and allocated to placebo or one of the 2 active treatment arms, according to a 1:1:1 randomization ratio, stratified at study entry by disease severity defined as baseline serum gamma glutamyl transferase (GGT) \< 2.5 x ULN or ≥ 2.5 x ULN). Accordingly, approximately 34 subjects will be allocated to each of the 3 treatment arms.

Study Record Dates

• First Submitted: June 30, 2017
• First Posted: July 21, 2017
• Study Start: June 26, 2017
• Primary Completion: April 11, 2019
• Study Completion: April 11, 2019
• Last Updated: June 29, 2022
• Results First Posted: March 31, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

BE (3); DE (5); IT (5); IL (6); US (21); GR (3); GB (9); ES (5); CA (4)