Study to Assess Safety & Efficacy of GKT137831 in Patients With Primary Biliary Cholangitis Receiving Ursodiol.
Primary Biliary Cirrhosis
About this trial
This is an interventional treatment trial for Primary Biliary Cirrhosis
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
- 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.
Sites / Locations
- Mayo Clinic
- University California Davis
- Ventura Clinical Trials
- Yale School of Medicine
- MedStar Georgetown University Hospital
- University of Miami
- Northwestern University
- Tulane University Medical Center
- Jackson Liver and GI Specialist c/o (STAR) LLC
- North Shore University Hospital
- NYU Hepatology Associates
- Mount Sinai Health System
- University of Rochester Medical Centre
- Dayton Gastroenterology Inc.
- University Hospitals Cleveland Medical Center
- UPMC Center for Liver Diseases
- Methodist University Hospital
- St Lukes Episcopal Hospital
- Pinnacle Clinical Research, PLLC
- Bon Secours Liver Institute of Hampton Roads
- Bon Secours Liver Institute of Richmond
- CUB Hôpital Erasme
- UZ Gent
- UZ Leuven
- University of Calgary Liver Unit
- University of Manitoba
- Centre hospitalier de l'Universite de Montreal (CHUM) Centre de Recherche Service d'Hepatologie
- McGill University Health Centre (MUHC)
- Friedrich-Alexander University Erlangen-Nürnberg
- Johann Wolfgang Goethe-University
- Universitatsklinikum Bonn
- Universitätsklinikum Heidelberg
- Universitätsmedizin Mainz
- General Hospital of Athens "Hippocratio"
- Laiko General Hospital
- University Hospital of Larissa
- Rambam Health Centre
- Shaare Zedek Medical Center
- Hadassah Medical Organization
- Rabin Medical Centre
- Sheba Medical Centre
- Sourasky Tel-Aviv Medical Center
- University of Milan-Bicocca
- Università Politecnica delle Marche - Facoltà di Medicina e Chirurgia
- Policlinico of Bologna
- San Giovanni Rotondo Hospital (Puglia)
- University Hospital Padova
- Hospital Clinic de Barcelona
- Hospital Puerta de Hierro-Majadahonda
- University of Alcalá
- Virgen De La Victoria University Hospital
- Hospital Universitario Virgen del Rocio
- Cambridge University Hospitals NHS Foundation Trust
- Plymouth Hospital NHS Trust
- Hull and East Yorkshire Hospitals NHS Trust
- Gloucestershire Royal Hospital
- Oxford University Hospitals NHS Foundation Trust
- Tayside Medical Science Centre (TASC)
- University Hospitals Birmingham NHS Foundation Trust
- King's College Hospital NHS Foundation Trust
- Singleton Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Placebo Comparator
GKT137831 400mg twice daily
GKT137831 400mg once daily
Placebo Arm
GKT137831 400mg twice daily Patients will self-administer 4 capsules in the morning and 4 capsules in the evening.
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.
Patients will self-administer 4 capsules in the morning and 4 capsules in the evening. All capsules will be placebos.