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

NCT04047160 | Completed Phase 1 DMC

• 2 other identifiers: OP-724-P101jRCT2031190073
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 2

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.

Conditions

Primary Biliary Cholangitis (PBC); Liver Cirrhosis, Biliary

Keywords

Primary Biliary Cholangitis (PBC); Liver Cirrhosis, Biliary; Cholangitis, Chronic Nonsuppurative Destructive; Liver Cirrhosis, Obstructive; Secondary Biliary Cholangitis; Primary Biliary Cirrhosis; Secondary Biliary Cirrhosis

Outcome Measures

Primary Outcomes (1)

• Occurrence Rate of Serious Adverse Events (Side Effects)

  Occurrence Rate of Serious Adverse Events (Side Effects) whose causal relationship with the investigational drug can not be denied. The data will be aggregated by each adverse event and cohort.

  28 days after the last administration of OP-724

Secondary Outcomes (13)

• Expression Ratio of Adverse Events

  28 days after the last administration of OP-724

• Percentage of Occurrence of Side Effects

  28 days after the last administration of OP-724

• Drug Concentration (OP-724 and C-82) in Plasma

  A) Single administration part: pre-dose and post-dose at 0.5, 1, 2, 4, 5, 9 and 24 hours. / B) Continuous administration part: pre-dose and post-dose at 4 hours on Day 1 and 4 in Cycle 1, 5, 9 and 12 (each cycle is 7 days)

• Parameters on Pharmacokinetics (OP-724 and C-82) : Maximum Plasma Concentration (Cmax)

  A) Single administration part: pre-dose and post-dose at 0.5, 1, 2, 4, 5, 9 and 24 hours. / B) Continuous administration part: pre-dose and post-dose at 4 hours on Day 1 and 4 in Cycle 1, 5, 9 and 12 (each cycle is 7 days)

• Parameters on Pharmacokinetics (OP-724 and C-82) : Area Under the Curve (AUC 0-24h)

  A) Single administration part: pre-dose and post-dose at 0.5, 1, 2, 4, 5, 9 and 24 hours. / B) Continuous administration part: pre-dose and post-dose at 4 hours on Day 1 and 4 in Cycle 1, 5, 9 and 12 (each cycle is 7 days)

Other Outcomes (1)

• Effectiveness: Serum Fibrosis Marker Level

  12 weeks after administration of OP-724

Study Arms (1)

OP-724

EXPERIMENTAL

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.

Drug: OP-724

Interventions

OP-724 DRUG

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

Also known as: CBP-beta-catenin inhibitor, PRI-724 (former name)

OP-724

Eligibility Criteria

• Age: 20 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• (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.
• Histologically, chronic non-suppurative destructive cholangitis (CNSDC) is found and the laboratory findings are consistent as PBC.
• A positive antimitochondrial antibody (AMA) with no histologic findings of CNSDC but showing a histology consistent with PBC.
• 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.

You may not qualify if:

• (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.

Sponsors & Collaborators

• Kiminori Kimura, MD: lead
• Ohara Pharmaceutical Co., Ltd.: collaborator
• Japan Agency for Medical Research and Development: collaborator

Study Sites (2)

Tokyo Metropolitan Komagome Hospital

Bunkyō-Ku, Tokyo, 113-8677, Japan

Location

Kyushu University Hospital

Fukuoka, 812-8582, Japan

Location

Related Publications (1)

• 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.

  PMID: 36442892 DERIVED

MeSH Terms

Conditions

Liver Cirrhosis, Biliary

Interventions

ICG 001

Condition Hierarchy (Ancestors)

Cholestasis, Intrahepatic; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Liver Diseases; Liver Cirrhosis; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Kiminori Kimura, MD

  Tokyo Metropolitan Komagome Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Head, Department of Hepatology

Study Record Dates

• First Submitted: July 30, 2019
• First Posted: August 6, 2019
• Study Start: August 29, 2019
• Primary Completion: September 21, 2021
• Study Completion: March 31, 2022
• Last Updated: July 7, 2022

Record last verified: 2022-07

Locations

JP (2)