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Primary Biliary CirrhosisPhase 2NCT03226067

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

A Phase 2 study testing GKT137831 in people with Primary Biliary Cirrhosis, run by Calliditas Therapeutics AB at 61 sites in 9 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Primary Biliary Cirrhosis
What is being tested?
GKT137831
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
111 participants
Where
61 sitesin 9 countries
Study dates
26 Jun 2017to 11 Apr 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 11Show fewer
  • 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.

Who cannot join

  • 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.
Show all 20Show fewer
  • 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.
  • A second or third degree atrioventricular block not successfully treated with a pacemaker.
  • History of cancer in the preceding 5 years, except adequately treated non-melanoma skin cancer, carcinoma in situ of the cervix, in situ prostate cancer, in situ breast ductal carcinoma, or superficial bladder cancer stage 0).
  • The occurrence of any acute infection requiring systemic antibiotic therapy within the 2 weeks prior the Screening Visit (Visit 1), or human immunodeficiency virus (HIV) infection.
  • A history of bone marrow disorder including aplastic anemia, or marked anemia defined as hemoglobin < 10.0 g/dL (or 6.2 mmol/L).
  • Any condition which, in the opinion of the Investigator, constitutes a risk or contraindication for the participation of the subject in the study, or which could interfere with the study objectives, conduct, or evaluation.

Trial locations and contacts

61 sites in 9 countries.

61 sites in 9 countries

United States21 sites

  • Dayton Gastroenterology Inc.

    Beavercreek, Ohio, 45440

  • Northwestern University

    Chicago, Illinois, 60611

  • University Hospitals Cleveland Medical Center

    Cleveland, Ohio, 44106

  • St Lukes Episcopal Hospital

    Houston, Texas, 77030

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

    Jackson, Mississippi, 39216

  • Pinnacle Clinical Research, PLLC

    Live Oak, Texas, 78233

  • North Shore University Hospital

    Manhasset, New York, 11030

  • Methodist University Hospital

    Memphis, Tennessee, 38104

  • University of Miami

    Miami, Florida, 33136

  • Yale School of Medicine

    New Haven, Connecticut, 06520-8019

  • Tulane University Medical Center

    New Orleans, Louisiana, 70112

  • NYU Hepatology Associates

    New York, New York, 10016

  • Mount Sinai Health System

    New York, New York, 10029

  • Bon Secours Liver Institute of Hampton Roads

    Newport News, Virginia, 23602

  • Mayo Clinic

    Phoenix, Arizona, 85054

  • UPMC Center for Liver Diseases

    Pittsburgh, Pennsylvania, 15213

  • Bon Secours Liver Institute of Richmond

    Richmond, Virginia, 23226

  • University of Rochester Medical Centre

    Rochester, New York, 14642

  • University California Davis

    Sacramento, California, 95817

  • Ventura Clinical Trials

    Ventura, California, 93003

  • MedStar Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

Other trials in United States

United Kingdom9 sites

  • University Hospitals Birmingham NHS Foundation Trust

    Birmingham, B152GW

  • Cambridge University Hospitals NHS Foundation Trust

    Cambridge, Cambridgeshire, CB2 0QQ

  • Tayside Medical Science Centre (TASC)

    Dundee, Tayside, DD19SY

  • Gloucestershire Royal Hospital

    Gloucester, Gloucestershire, GL13NN

  • Hull and East Yorkshire Hospitals NHS Trust

    Hull, East Yorkshire, HU3 2JZ

  • King's College Hospital NHS Foundation Trust

    London, SE5 9RS

  • Oxford University Hospitals NHS Foundation Trust

    Oxford, Oxfordshire, OX3 9DU

  • Plymouth Hospital NHS Trust

    Plymouth, Devon, PL6 8DH

  • Singleton Hospital

    Swansea, SA28PP

Other trials in United Kingdom

Israel6 sites

  • Rambam Health Centre

    Haifa, 3109601

  • Shaare Zedek Medical Center

    Jerusalem, 9103102

  • Hadassah Medical Organization

    Jerusalem, 91120

  • Rabin Medical Centre

    Petach-Tiqva, 49100

  • Sheba Medical Centre

    Ramat Gan, 52621

  • Sourasky Tel-Aviv Medical Center

    Tel Aviv, 3906

Other trials in Israel

Germany5 sites

  • Universitatsklinikum Bonn

    Bonn, North Rhine-Westphalia, 53105

  • Friedrich-Alexander University Erlangen-Nürnberg

    Erlangen, Bavaria, 91054

  • Johann Wolfgang Goethe-University

    Frankfurt am Main, Hesse, 60590

  • Universitätsklinikum Heidelberg

    Heidelberg, D-69210

  • Universitätsmedizin Mainz

    Mainz, D-55131

Other trials in Germany

Italy5 sites

  • Università Politecnica delle Marche - Facoltà di Medicina e Chirurgia

    Ancona, 60126

  • Policlinico of Bologna

    Bologna, 40138

  • San Giovanni Rotondo Hospital (Puglia)

    Foggia, 71013

  • University of Milan-Bicocca

    Monza, Lombardy, 20900

  • University Hospital Padova

    Padova, 35128

Other trials in Italy

Spain5 sites

  • Hospital Clinic de Barcelona

    Barcelona, 8036

  • Hospital Puerta de Hierro-Majadahonda

    Madrid, 28222

  • University of Alcalá

    Madrid, 28223

  • Virgen De La Victoria University Hospital

    Málaga, 29015

  • Hospital Universitario Virgen del Rocio

    Seville, 41013

Other trials in Spain

Canada4 sites

  • University of Calgary Liver Unit

    Calgary, Alberta, T2N4z6

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

    Montreal, Quebec, H2X0A9

  • McGill University Health Centre (MUHC)

    Montreal, Quebec, H4A3J1

  • University of Manitoba

    Winnipeg, Manitoba, R3E3P4

Other trials in Canada

Belgium3 sites

  • CUB Hôpital Erasme

    Brussels, 1070

  • UZ Gent

    Ghent, 9000

  • UZ Leuven

    Leuven, 3000

Other trials in Belgium

Greece3 sites

  • General Hospital of Athens "Hippocratio"

    Athens, 11527

  • Laiko General Hospital

    Athens, 11527

  • University Hospital of Larissa

    Larissa, 41100

Other trials in Greece

About this study

Official title: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial to Assess the Efficacy & Safety of Oral GKT137831 in Patients With Primary Biliary Cholangitis Receiving Ursodeoxycholic Acid and With Persistently Elevated Alkaline Phosphatase

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).

Read the detailed description

Primary biliary cholangitis (PBC) is a disease of the liver. It is caused a sustained attack by the body's immune system on the bile ducts (canals) inside the liver. This continuous assault leads to their gradual destruction and eventual disappearance. This results in obstruction to the flow of bile which gets worse with disease progression. Once the bile duct injury has been established, the disease progresses due to ongoing obstruction of bile flow, inflammation and scarring of the liver tissue(fibrosis). The liver eventually fails.

This research is looking into whether the study drug is better than a dummy drug when given to patients with PBC. This trial will monitor the patients taking part with regular blood tests and ultrasound liver scans before, during, and at the end of the trial. These measures will allow for the ongoing assessment of liver function, and liver stiffness. It is hoped that in patients in whom the study drug is beneficial, the liver function or stiffness may progress at a slower pace, or may even improve during or at the end of the trial. Liver injury, inflammation and fibrosis Participants will be randomly assigned to 1 of 3 treatment groups (active drug once daily, active drug twice daily or placebo). This is a double blinded study so neither the participants nor the staff responsible for their care will know which group they have been assigned to. During the treatment period, participants will take 4 capsules orally at home in the morning and 4 capsules in the evening for 24 weeks.

Participants will be in the trial for 32 weeks in total (about 8 months) and will attend approximately 8 clinic visits.

Being tested
GKT137831, Placebo oral capsule
Medical subject headings
Liver Cirrhosis, Biliary

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GKT137831Drug

    Also called setanaxib

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

  • Placebo oral capsuleDrug

    Also called Placebo

    Matching capsules.

Study groups in NCT03226067
Study groupRoleWhat they receive
GKT137831 400mg twice dailyExperimentalGKT137831 400mg twice daily Patients will self-administer 4 capsules in the morning and 4 capsules in the evening.
Receives: Drug: GKT137831
GKT137831 400mg once dailyExperimentalGKT137831 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.
Receives: Drug: GKT137831; Drug: Placebo oral capsule
Placebo ArmPlacebo comparatorPatients will self-administer 4 capsules in the morning and 4 capsules in the evening. All capsules will be placebos.
Receives: Drug: Placebo oral capsule

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The Percent Change in Serum GGT.

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

    Measured: Baseline to week 24 (visit 7)

Secondary outcomes (17)

  1. Absolute Change in Serum GGT

    Absolute change in serum GGT from baseline to each assessment.

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

  2. Percent Change in Serum GGT

    Percent change in serum GGT from baseline to each assessment (serum GGT was measured in U/L)

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

  3. Percent Change in Serum ALP

    Percent change in serum ALP from baseline to each assessment (serum ALP was measured in U/L).

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

  4. Absolute Change in Serum ALP

    Absolute change in serum ALP from baseline to each assessment.

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

  5. Absolute Change in Serum Conjugated Bilirubin.

    Absolute change in serum conjugated bilirubin from baseline to each assessment.

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

  6. Percent Change in Serum Conjugated Bilirubin.

    Percent change in serum Conjugated bilirubin, from baseline to each assessment (serum conjugated bilirubin is measured in μmol/L).

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

  7. Absolute Change in Serum Total Bilirubin.

    Absolute change in serum total bilirubin, from baseline to each assessment.

    Measured: from baseline to Weeks 2, 6, 12, 18 and 24

  8. Percent Change in Serum Total Bilirubin.

    Percent change in Serum Total Bilirubin from baseline to each assessment (serum total bilirubin is measured in μmol/L).

    Measured: from baseline to Weeks 2, 6, 12, 18 and 24

  9. Absolute Change in Liver Stiffness as Assessed by Transient Elastography (FibroScan® or Similar Technology).

    Absolute change in liver stiffness as assessed by transient elastography (FibroScan® or similar technology), from baseline to Week 24, in subjects with values at baseline and Week 24.

    Measured: From baseline to Week 24, in patients with values at baseline and Week 24.

  10. Percent Change in Liver Stiffness as Assessed by Transient Elastography (FibroScan® or Similar Technology).

    Percent change in liver stiffness as assessed by transient elastography (FibroScan® or similar technology), from baseline to Week 24, in subjects with values at baseline and Week 24 (liver stiffness is measured in kPa).

    Measured: From baseline to Week 24, in patients with values at baseline and Week 24.

  11. Percent Change in Serum Levels of Collagen Fragments Indicative of Collagen Formation and Degradation.

    Percent change in serum levels of collagen fragments indicative of collagen formation and degradation, from baseline to Weeks 12 and 24 (serum levels of collagen fragments are measured in ng/mL).

    Measured: From baseline to Weeks 12 and 24.

  12. Absolute Change in Liver Stiffness as Assessed by Transient Elastography by Subgroup (FibroScan® or Similar Technology).

    Absolute change in liver stiffness by subgroup (>=9.6 kPa) as assessed by transient elastography (FibroScan® or similar technology), from baseline to Week 24, in subjects with values at baseline and Week 24.

    Measured: From baseline to Week 24, in patients with values at baseline and Week 24.

  13. Percent Change in Liver Stiffness as Assessed by Transient Elastography by Subgroup (FibroScan® or Similar Technology).

    Percent change in liver stiffness by subgroup (>=9.6 kPa) as assessed by transient elastography (FibroScan® or similar technology), from baseline to Week 24, in subjects with values at baseline and Week 24 (liver stiffness is measured in kPa).

    Measured: From baseline to Week 24, in patients with values at baseline and Week 24.

  14. Absolute Change in Pruritis Visual Analogue Scale (VAS) Scores

    Absolute Change in Pruritis Visual Analogue Scale (VAS) scores from baseline to weeks 12 and 24- Score from 0 to 10, 0= no itch and 10= severe itch, continuous, day and night intolerable itch.

    Measured: From baseline to Weeks 12 and 24

  15. Percent Change in Pruritis Visual Analogue Scale (VAS) Scores

    Percent Change in Pruritis Visual Analogue Scale (VAS) scores from baseline to weeks 12 and 24- Score from 0 to 10, 0= no itch and 10= severe itch, continuous, day and night intolerable itch.

    Measured: From baseline to Weeks 12 and 24

  16. Absolute Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores

    Absolute Change in PBC-40 Domain scores from baseline to weeks 12 and 24 Symptoms domain: items 1 to 7 of the PBC-40 questionnaire (score from 6 to 35). Itch domain: items 8 to 10 of the PBC-40 questionnaire (score from 0 to 15). Fatigue domain: items 11 to 21 of the PBC-40 questionnaire (score from 11 to 55). Cognitive domain: items 22 to 27 of the PBC-40 questionnaire (score from 6 to 30). Emotional domain: items 28, 30 and 33 of the PBC-40 questionnaire (score from 3 to 15). Social domain: items 29, 31, 32, 34 to 40 of the PBC-40 questionnaire (score from 8 to 50). Higher scores mean worse outcome.

    Measured: From baseline to Weeks 12 and 24

  17. Percent Change in PBC-40 (Primary Biliary Cholongitis) Domain Scores

    Percent Change in PBC-40 Domain scores from baseline to weeks 12 and 24 Symptoms domain: items 1 to 7 of the PBC-40 questionnaire (score from 6 to 35). Itch domain: items 8 to 10 of the PBC-40 questionnaire (score from 0 to 15). Fatigue domain: items 11 to 21 of the PBC-40 questionnaire (score from 11 to 55). Cognitive domain: items 22 to 27 of the PBC-40 questionnaire (score from 6 to 30). Emotional domain: items 28, 30 and 33 of the PBC-40 questionnaire (score from 3 to 15). Social domain: items 29, 31, 32, 34 to 40 of the PBC-40 questionnaire (score from 8 to 50). Higher scores mean worse outcome.

    Measured: From baseline to Weeks 12 and 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jul 2017
  2. Study start26 Jun 2017
  3. Primary completion11 Apr 2019
  4. Study completion11 Apr 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
111 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03226067
Sponsor's protocol ID
GSN000300
Other IDs
2016-004599-23, 2016
Status last verified
Mar 2022
First submitted
30 Jun 2017
Last updated
29 Jun 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 37183520

  • 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.

    PubMed 36809195

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing GKT137831 in people with Primary Biliary Cirrhosis, run by Calliditas Therapeutics AB at 61 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 61 sites in United States, United Kingdom, Israel, Germany, Italy and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Mar 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The Percent Change in Serum GGT. (time frame: Baseline to week 24 (visit 7)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03226067, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2022.

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