Safety, Tolerability of CBP / Beta-Catenin Inhibitor OP-724 in Patients With Primary Biliary Cholangitis (Phase I)

JRCT ID: jRCT2031190073

Registered date:08/08/2019

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Primary Biliary Cholangitis (PBC)
• Date of first enrollment: 04/09/2019
• Target sample size: 12
• Study type: Interventional

Intervention(s)

Drug: OP-724 400 mg / 20 mL / vial (20 mg / mL)

Dose:(Level 1) 140 mg / m2 / 4 hours
(Level 2) 280 mg / m2 / 4 hours (starting dose)
(Level 3) 380 mg / m2 / 4 hours

Administration method:
Continuous intravenous administration will be done for 4 hours twice a week. This procedure will be as one cycle and 12 cycles (12 weeks in total) will be conducted .
On 7 days prior to the first cycle administration, a dose scheduled in the first cycle will be administered with continuous intravenous for 4 hours and the safety and pharmacokinetics on the day of administration to the next day after administration will be evaluated.

Outcome(s)

Primary Outcome

Occurrence rate of serious adverse events (side effects) whose causal relationship with
the investigational drug can not be denied.

Secondary Outcome

[Secondary Outcome Measures]
(1) Adverse event occurrence rate
(2) Proportion of side effects
(3) Pharmacokinetics (OP-724 and C-82)
(4) Amount of change from baseline in liver tissue fibrotic area ratio by liver biopsy at
12 weeks after administration
(5) Amount of change from baseline of liver stiffness by Fibro Scan at 12 weeks after
administration
(6) Amount of change from baseline of Child-Pugh Score at 12 weeks after
administration
(7) Amount of change from baseline in MELD score at 12 weeks after administration
(8) Amount of change from baseline of modified Histological Activity Index (HAI) and
classification of Nakanuma et al. By liver biopsy at 12 weeks after administration
(9) Amount of change from baseline in serum ALP level at 12 weeks after
administration
(10) Amount of change from baseline in serum Total Bilirubin value at 12 weeks after
administration
(11) Amount of change from baseline of ELF score at 12 weeks after administration

[Exploratory Outcome Measures]
Effectiveness: Amount of change from baseline in serum fibrosis marker level at 12
weeks after administration

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: < 75age old
• Gender: Both

Include criteria

(1) Of the confirmed patients*of primary biliary cholangitis, patients with progressive fibrosis (Scheuer classification stage III or higher) by liver tissue examination

* The diagnosis of primary biliary cholangitis (PBC) is based on the diagnostic criteria (2015) of <Study and research on refractory liver and biliary diseases>. That is, one that corresponds to any one of the following is diagnosed as PBC.
1) Histologically, chronic non-suppurative destructive cholangitis (CNSDC) is found and the laboratory findings are consistent as PBC
2) A positive antimitochondrial antibody (AMA) with no histologic findings of CNSDC but showing a histology consistent with PBC
3) There is no experience of histologic search, but AMA is positive and it is considered as PBC from clinical image and course

(2) Patients with Performance Status 0 to 2
(3) Patients aged 20 years or over and under 75 when acquiring informed consent
(4) Regarding participation in this trial (including liver biopsy), patients who obtained informed consent by
their own voluntary intention

Exclude criteria

(1)Patients who have liver fibrosis other than primary biliary cholangitis or patients whose cause of liver fibrosis is unknown
(2)Patients with esophageal gastric varices determined to be treated by endoscopic examination at screening
(3)Patients with complication or previous history of primary liver cancer (excluding those who have had
more than one year of hepatocarcinoma resection/radiofrequency ablation)
(4)Merger of malignant tumor or past patients (within 3 years before screening)
However, the following diseases are excluded: treated basal cell carcinoma, treated lung intraepithelial carcinoma, treated cervical carcinoma, or control superficial (not invasive) bladder carcinoma
(5)Patients who can not be denied HBV, HCV, HIV, HTLV-1 or syphilis
(6)Serum creatinine value: Patients with more than 1.5 times the upper limit of the facility reference value
(7)Patients with poor control of diabetes, hypertension or heart failure
(8)Patients with psychiatric diseases judged to have the potential to influence the implementation of clinical trials
(9)Patients who have severe allergy to or contrast media
(10) Patients whose dosage regimen was changed within 12 weeks prior to enrollment
(11) Patients who have history of drug or alcohol intoxication within 5 years before acquiring informed consent or who have history of drug or alcohol abuse within the past year
(12) Patients who participated in other clinical trials and clinical trials within 30 days prior to acquisition of consent, patients who used investigational drugs or investigational equipment
(13) Patients who received liver transplantation or other organ transplantation (including bone marrow
transplantation) and patients who are difficult to intravenouslyadminister
(14) Patients whose liver biopsy is expected to be difficult to perform
(15) Patients who are pregnant or nursing, or who are likely to become pregnant
(16) Male patients who do not obtain consent to contraception from the time of acquiring informed consent
until the end of 12 weeks after the administration of investigational drug
(17) In addition, patients investigated by investigators or clinical trial doctors as judged unsuitable for this
trial

Related Information

• Primary Sponsor: Kimura Kiminori
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development
• Secondary ID(s): NCT04047160