Clemizole HCl for Subjects With Hepatocellular Carcinoma

NCT03069508 | Unknown Phase 2 FDA Drug

• 1 other identifier: EIG-234
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a phase IIa open label pilot study of up to six months treatment with clemizole hydrochloride (200 mg vs. 300 mg vs. 400 vs. 500 mg mg) given orally TID to subjects with hepatocellular carcinoma that are either awaiting transplantation or have an unresectable lesion.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (4)

• Number of participants with adverse events

  Safety and tolerability of up to six months of treatment with clemizole hydrochloride thrice daily by mouth in subjects diagnosed with hepatocellular carcinoma that are either awaiting transplantation or have an unresectable lesion, determined by the number of participants with abnormal laboratory values and/or adverse events that are related to treatment

  Number of recorded adverse events at six months

• Overall tumor response according to radiologic assessments associated with clemizole HCl.

  Number of participants with stable disease, complete response (CR), partial response (PR), or minor response (MR), as defined by Response Evaluation Criteria in Solid Tumors (RECIST), associated with clemizole HCl.

  Change from baseline up to 24 weeks

• AUC Pharmacokinetic (PK) assessment of clemizole hydrochloride (200 mg vs. 300 mg vs. 400 mg vs. 500 mg by mouth)

  Area under the plasma concentration versus time curve (AUC) of clemizole HCl following oral administration of 200 mg vs. 300 mg vs. 400 mg vs. 500 mg.

  0-pre-dose, post dose: 15 min, 30 min, 60 min, 90 min, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours post oral administration of clemizole HCl for those subjects participating in the PK portion of this trial

• Cmax Pharmacokinetic (PK) assessment of clemizole hydrochloride (200 mg vs. 300 mg vs. 400 mg vs. 500 mg by mouth)

  Peak plasma concentration (Cmax) of clemizole HCl following oral administration of 200 mg vs. 300 mg vs. 400 mg vs. 500 mg.

  0-pre-dose, post dose: 15 min, 30 min, 60 min, 90 min, 2 hours, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours post oral administration of clemizole HCl for those subjects participating in the PK portion of this trial

Secondary Outcomes (4)

• Duration of response associated with clemizole hydrochloride

  First administration of study drug until progressive disease in patients with objective responses up to 24 weeks.

• Time to progression associated with clemizole hydrochloride

  First administration of study drug until progressive disease up to 24 weeks.

• Duration of stable disease associated with clemizole hydrochloride

  First day of receiving clemizole until progressive disease or response up to 24 weeks.

• Overall survival associated with clemizole hydrochloride

  First day of receiving study medication to death up to 24 weeks.

Study Arms (4)

200 mg TID

EXPERIMENTAL

200 mg clemizole hydrochloride will be administered orally thrice a day for 24 weeks.

Drug: Clemizole Hydrochloride

300 mg TID

EXPERIMENTAL

300 mg clemizole hydrochloride will be administered orally thrice a day for 24 weeks.

Drug: Clemizole Hydrochloride

400 mg TID

EXPERIMENTAL

400 mg clemizole hydrochloride will be administered orally thrice a day for 24 weeks.

Drug: Clemizole Hydrochloride

500 mg TID

EXPERIMENTAL

500 mg clemizole hydrochloride will be administered orally thrice a day for 24 weeks.

Drug: Clemizole Hydrochloride

Interventions

Clemizole Hydrochloride DRUG

Clemizole Hydrochloride will be administered orally for up to 24 weeks

Also known as: Clemizole

200 mg TID; 300 mg TID; 400 mg TID; 500 mg TID

Eligibility Criteria

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

You may qualify if:

• Males or females, at least 18 years of age.
• Subjects should have a diagnosis (histologically proven) of hepatocellular carcinoma (that is measurable on CT or MR with contrast) and are either awaiting transplantation or have an unresectable lesion for which they have not received prior experimental systemic treatments for HCC and no additional therapy is planned.
• Eastern Cooperative Oncology Group performance status of 2 or less.
• Child-Pugh (CP) score of A or B.
• Life expectancy of at least 12 weeks.
• Elevated alphafetoprotein (AFP) level .
• Adequate hematologic (platelet count, ≥60 ; hemoglobin, ≥8.5 g per deciliter; and prothrombin time international normalized ratio, ≤2.3; or prothrombin time, ≤6 seconds above control), hepatic (albumin, ≥2.8 g per deciliter; total bilirubin, ≤3 mg per deciliter \[51.3 μmol per liter\]; and alanine aminotransferase and aspartate aminotransferase, ≤5 times the upper limit of the normal range), and renal (serum creatinine, ≤1.5 times the upper limit of the normal range) function.
• Electrocardiogram (ECG) showing no acute ischemia or clinically significant abnormality and a QT/QTc interval \<450 milliseconds for males or \<470 milliseconds for females using Bazett's correction (QTc =QT/RR0.5;ICH Guidance E14 Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs)
• Females of childbearing potential (intact uterus and within one year since the last menstrual period) should be non-lactating and have a negative serum pregnancy test. In addition, all subjects (male and female) and their sexually active partners should agree to use one of the following acceptable birth control methods throughout the study:
• surgical sterilization (bilateral tubal ligation, hysterectomy, bilateral oophorectomy) six month minimum
• IUD in place for at least three months
• barrier methods (condom or diaphragm) with spermicide
• surgical sterilization of the partner (vasectomy for six months)
• hormonal contraceptives for at least three months prior to the first dose of study drug
• Willing and able to comply with study procedures and provide written informed consent

You may not qualify if:

• Participation in a clinical trial with or use of any investigational agent within 30 days of Study Visit 1
• Patients co-infected with HIV
• Patients with screening tests positive for anti-HIV Ab
• Patients with tumors of mixed histology or fibrolamellar variant,
• Pregnant or lactating women,
• Patients requiring systemic anticancer therapy, or biologic-response modifiers
• Medical/psychological/social problems that might affect study participation or evaluations
• Eating disorder or alcohol abuse within the past two years, excessive alcohol intake (\>20 g per day for females (1.5 standard alcohol drinks) or \>30 g per day for males (2.0 standard alcohol drinks) (a standard drink contains 14 g of alcohol: 12 oz of beer, 5 oz of wine or 1.5 oz of spirits) (1.0 fluid oz (US) = 29.57 mL) or if in the opinion of the investigator, an alcohol use pattern that will interfere with study conduct
• Drug abuse within the last six months
• Patients with absolute neutrophil count (ANC) \<1500 cells/mm3;
• Abnormal TSH, T4 or T3
• History or clinical evidence of any of the following:
• variceal bleeding, difficult to treat ascites, hepatic encephalopathy, CTP score \>8,
• immunologically mediated disease (e.g, rheumatoid arthritis, inflammatory bowel disease, severe psoriasis, systemic lupus erythematosus) requiring more than intermittent non-steroidal anti-inflammatory medications for management or that requires frequent or prolonged use of corticosteroids (inhaled asthma medications are allowed)
• significant or unstable cardiac disease (e.g., angina, congestive heart failure, uncontrolled hypertension, history of arrhythmia)

Sponsors & Collaborators

• Eiger Group International, Inc.: lead

Study Sites (1)

University of Ankara

Ankara, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

clemizole

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Cihan Yurdaydin, MD

  University of Ankara

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2017
• First Posted: March 3, 2017
• Study Start: February 13, 2017
• Primary Completion: December 31, 2017
• Study Completion: January 31, 2018
• Last Updated: March 3, 2017

Record last verified: 2017-02

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)