Safety, Tolerability of OP-724 in Patients With Primary Biliary Cholangitis (Phase I)

NCT ID: NCT04047160

Last Updated: 2022-07-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-29
• Study Completion Date: 2022-03-31

Brief Summary

To evaluate the safety and pharmacokinetics of OP-724 and to determine the recommended dose of OP-724 against Primary Biliary Cholangitis patients.

Detailed Description

This trial is a phase I trial aimed at examining the safety and tolerability of OP-724 in patients with primary biliary cholangitis and determining the recommended dose.

The subjects are patients diagnosed with primary biliary cholangitis and diagnosed as progress of fibrosis (Scheuer stage III or higher) as a result of liver tissue examination. As a dosing schedule, OP-724 is intravenously administered twice a week (4 hours) for 12 weeks. However, once 7 days prior to the first cycle of administration, a dose scheduled for the first cycle will be administered once by continuous intravenous administration for 4 hours, and safety and pharmacokinetics will be evaluated on the day of administration to the next day after administration. The dose level shall be 3 doses (140 mg/m2/4hrs, 280 mg/m2/4hrs [starting dose], 380 mg/m2/4hrs), of which 2 doses shall be registered for up to 6 patients each. The safety and pharmacokinetic data after OP-724 administration will be decided comprehensively to determine the recommended dose in the next phase.

Conditions

Primary Biliary Cholangitis (PBC); Liver Cirrhosis, Biliary

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

OP-724

Dose: 140, 280, 380 mg/m2/4 hrs

Administration method:

[Level 1] 140 mg/m2/4 hours [Level 2] 280 mg/m2/4 hours (starting dose) [Level 3] 380 mg/m2/4 hours 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.

Group Type: EXPERIMENTAL

OP-724

Intervention Type: DRUG

Twice a week for 4 hours continuous intravenous administration of OP-724

Interventions

OP-724

Twice a week for 4 hours continuous intravenous administration of OP-724

Intervention Type: DRUG

Other Intervention Names

CBP-beta-catenin inhibitor; PRI-724 (former name)

Eligibility Criteria

Inclusion Criteria

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

• 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.

Exclusion 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 hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), human T-cell leukemia virus 1 (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 intravenously administer.
• (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.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 74 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ohara Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Japan Agency for Medical Research and Development

OTHER_GOV

Sponsor Role: collaborator

Kiminori Kimura, MD

OTHER

Sponsor Role: lead

Responsible Party

Kiminori Kimura, MD

Head, Department of Hepatology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Kiminori Kimura, MD

Role: PRINCIPAL_INVESTIGATOR

Tokyo Metropolitan Komagome Hospital

Locations

Tokyo Metropolitan Komagome Hospital

Bunkyō-Ku, Tokyo, Japan

Kyushu University Hospital

Fukuoka, , Japan

Countries

Japan

References

Kimura M, Ogawa E, Harada K, Imamura J, Saio M, Ikura Y, Yatsuhashi H, Murata K, Miura K, Ieiri I, Tanaka A, Kimura K. Feasibility, safety and tolerability of the CREB-binding protein/beta-catenin inhibitor OP-724 in patients with advanced primary biliary cholangitis: an investigator-initiated, open-label, non-randomised, two-centre, phase 1 study. BMJ Open Gastroenterol. 2022 Nov;9(1):e001001. doi: 10.1136/bmjgast-2022-001001.

Reference Type: DERIVED

PMID: 36442892 (View on PubMed)

Other Identifiers

jRCT2031190073

Identifier Type: OTHER

Identifier Source: secondary_id

OP-724-P101

Identifier Type: -

Identifier Source: org_study_id