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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: ClinicalTrials.gov
Last refreshed on: 12 December 2020
Main ID:  NCT03226067
Date of registration: 30/06/2017
Prospective Registration: Yes
Primary sponsor: Genkyotex SA
Public title: Study to Assess Safety and Efficacy of GKT137831 in Patients With Primary Biliary Cholangitis Receiving Ursodeoxycholic Acid.
Scientific title: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial to Assess the Efficacy and Safety of Oral GKT137831 in Patients With Primary Biliary Cholangitis Receiving Ursodeoxycholic Acid and With Persistently Elevated Alkaline Phosphatase
Date of first enrolment: June 26, 2017
Target sample size: 111
Recruitment status: Completed
URL:  https://clinicaltrials.gov/show/NCT03226067
Study type:  Interventional
Study design:  Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).  
Phase:  Phase 2
Countries of recruitment
Belgium Canada Germany Greece Israel Italy Spain United Kingdom
United States
Contacts
Key inclusion & exclusion criteria

Inclusion Criteria:

1. Male or female aged 18 to 80 years, inclusive.

2. Willing and able to give written informed consent and to comply with the requirements
of the study.

3. 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.

4. Serum ALP = 1.5 x ULN.

5. Serum GGT = 1.5 x ULN.

6. UDCA treatment for at least 6 months and stable dose for at least 3 months prior to
Visit 1.

7. 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.

8. 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:

1. A positive pregnancy test or breast-feeding for female subjects.

2. Any hepatic decompensation, defined as a past or current history of hepatic
encephalopathy, gastrointestinal tract bleeding due to esophageal varices, or ascites.

3. International normalized ratio (INR) > 1.2 unless subject is on anticoagulant therapy.

4. ALT > 3 x ULN.

5. Total bilirubin > 1 x ULN.

6. Planned or current plasmapheresis or other extra-corporeal treatments (e.g., molecular
adsorbent recirculation system (MARS)) for treatment-refractory pruritus.

7. History of liver transplantation, current placement on a liver transplant list or
current Model for End Stage Liver Disease (MELD) score = 15.

8. Cirrhosis with complications, including history or presence of: spontaneous bacterial
peritonitis, hepatocellular carcinoma.

9. Hepatorenal syndrome (type I or II) or Screening serum creatinine > ULN.

10. 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).

11. 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.

12. Treatment with any investigational agent within 4 weeks of Visit 1 or 5 half-lives of
the investigational medicinal product (whichever is longer).

13. A history of long QT syndrome.

14. 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.

15. 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).

16. 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.

17. A history of bone marrow disorder including aplastic anemia, or marked anemia defined
as hemoglobin < 10.0 g/dL (or 6.2 mmol/L).

18. 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.



Age minimum: 18 Years
Age maximum: 80 Years
Gender: All
Health Condition(s) or Problem(s) studied
Primary Biliary Cirrhosis
Intervention(s)
Drug: GKT137831
Drug: Placebo oral capsule
Primary Outcome(s)
The percent change in serum GGT. [Time Frame: Baseline to week 24 (visit 7)]
Secondary Outcome(s)
Absolute change in AST to Platelet Ratio Index (APRI) scores [Time Frame: from baseline to Weeks 2, 6, 12, 18, 24 and 28]
Absolute change in Enhanced Liver Fibrosis (ELF) score [Time Frame: From baseline to Weeks 12 and 24.]
Absolute change in liver stiffness as assessed by transient elastography (FibroScan® or similar technology). [Time Frame: From baseline to Week 24, in patients with values at baseline and Week 24.]
Absolute change in serum Alanine Aminotransferase (ALT) [Time Frame: From baseline to Weeks 2, 6, 12, 18, 24 and 28]
Absolute change in serum ALP [Time Frame: From baseline to Weeks 2, 6, 12, 18, 24 and 28]
Absolute change in serum Aspartate Aminotransferase (AST) [Time Frame: From baseline to Weeks 2, 6, 12, 18, 24 and 28]
Absolute change in serum conjugated bilirubin. [Time Frame: From baseline to Weeks 2, 6, 12, 18, 24 and 28]
Absolute change in serum GGT [Time Frame: From baseline to Weeks 2, 6, 12, 18, 24 and 28]
Absolute change in serum levels of collagen fragments indicative of collagen formation and degradation. [Time Frame: From baseline to Weeks 12 and 24.]
Absolute change in serum levels of fibrinogen [Time Frame: From baseline to Weeks 2, 6, 12, 18, 24 and 28]
Absolute change in serum levels of high-sensitivity C-reactive protein (hsCRP) [Time Frame: From baseline to Weeks 2, 6, 12, 18, 24 and 28]
Absolute change in serum total bilirubin. [Time Frame: from baseline to Weeks 2, 6, 12, 18, 24 and 28]
Absolute change in the Fibrosis-4 (FIB-4) [Time Frame: from baseline to Weeks 2, 6, 12, 18, 24 and 28]
Absolute change in total bile acids [Time Frame: From baseline to Week 12 and 24.]
Percent change in AST to Platelet Ratio Index (APRI) scores [Time Frame: from baseline to Weeks 2, 6, 12, 18, 24 and 28]
Percent change in liver stiffness as assessed by transient elastography (FibroScan® or similar technology). [Time Frame: From baseline to Week 24, in patients with values at baseline and Week 24.]
Percent change in serum Alanine Aminotransferase (ALT) [Time Frame: From baseline to Weeks 2, 6, 12, 18, 24 and 28]
Percent change in serum ALP [Time Frame: From baseline to Weeks 2, 6, 12, 18, 24 and 28]
Percent change in serum Aspartate Aminotransferase (AST) [Time Frame: From baseline to Weeks 2, 6, 12, 18, 24 and 28]
Percent change in serum conjugated bilirubin. [Time Frame: From baseline to Weeks 2, 6, 12, 18, 24 and 28]
Percent change in serum GGT [Time Frame: Fom baseline to Weeks 2, 6, 12, 18, 24 and 28]
Percent change in serum levels of collagen fragments indicative of collagen formation and degradation. [Time Frame: From baseline to Weeks 12 and 24.]
Percent change in serum levels of fibrinogen [Time Frame: From baseline to Weeks 2, 6, 12, 18, 24 and 28]
Percent change in serum levels of high-sensitivity C-reactive protein (hsCRP) [Time Frame: From baseline to Weeks 2, 6, 12, 18, 24 and 28]
Percent change in serum total bilirubin. [Time Frame: from baseline to Weeks 2, 6, 12, 18, 24 and 28]
Percent change in the Fibrosis-4 (FIB-4) [Time Frame: from baseline to Weeks 2, 6, 12, 18, 24 and 28]
Percent change in total bile acids [Time Frame: From baseline to Week 12 and 24.]
Secondary ID(s)
2016-004599-23
GSN000300
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
Ethics review
Results
Results available:
Date Posted:
Date Completed:
URL:
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