Clinical Trials List
Protocol NumberYIV-906-2018L1
NCT Number(ClinicalTrials.gov Identfier)NCT04000737
2019-08-01 - 2024-10-30
Phase II
Recruiting7
ICD-10C22.0
Liver cell carcinoma
A Phase II Randomized Placebo Controlled Study Investigating The Combination Of YIV-906 And Sorafenib (Nexavar®) In HBV (+) Patients With Advanced Hepatocellular Carcinoma
-
Trial Applicant
IQVIA RDS Taiwan Ltd.
-
Sponsor
Yiviva Inc
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Wei-Hong Cheng NA
- Ming-Zhe Tay Digestive System Department
- Tsu-Yi Chao NA
- Ming-Yao Chen NA
- HUI-WEN LIU NA
- Yao-Yu Hsieh NA
- 李宗穎 Digestive System Department
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Rheun-Chuan Lee NA
- Chien-An Liu NA
- Yee Chao 無
- Chung-Pin Li NA
- 姜乃榕 NA
- Yi-Ping Hung NA
- Pei-Chang Lee NA
- CHUN-YING WU NA
- Ming-Huang Chen NA
- Yi-Hsiang Huang NA
- I-Cheng Lee NA
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Chiu Hung Chiu NA
- 劉奕廷 NA
- 簡世杰 NA
- 顏志傑 NA
- Yih-Jyh Lin NA
The Actual Total Number of Participants Enrolled
0 Recruiting
Principal Investigator
Co-Principal Investigator
- Huey-En Tzeng NA
- 黃奕文 NA
- 夏和雄 NA
- Wei-Yu Kao Digestive System Department
- Cheng-I Hsieh NA
- Kuan-Der Lee Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Hsueh-Chou Lai Digestive System Department
- Po-Heng Chuang Digestive System Department
- 許士超 Division of General Surgery
- Cheng-Yuan Peng Digestive System Department
- Hung-Wei Wang NA
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 呂嘉偉 NA
- 吳庭榕 NA
- Wei-Chen Lee NA
- 周宏學 未分科
- 周宏學 NA
- Shi-Ming Lin NA
- Jen-Shi Chen NA
- 王瑜肇 NA
- Kun-Ming Chan NA
- 李兆偉 NA
- 吳宗翰 NA
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
HBV
Objectives
Primary objectives:
• To determine the progression free survival (PFS) in each arm
Secondary objectives:
• To determine the time to progression (TTP) in each arm
• To assess the objective response rate (ORR) in each arm
• To assess the disease control rate (DCR) in each arm
• To determine the overall survival (OS)
• To assess the safety and tolerability of the combination of YIV-906 plus sorafenib
as measured by the rate and severity of AEs.
• To measure the change of quality of life (QoL) in each arm
• To determine the effect of YIV-906 on sorafenib PK
Test Drug
YIV-906
Active Ingredient
YIV-906
Dosage Form
Capsule
Dosage
200 mg
Endpoints
Primary endpoints
• To determine the effect of YIV-906 on progression-free survival (PFS). PFS
measured as time from randomization to progression according to RECIST 1.1 and mRECIST
(based on Investigator assessment) or death due to any cause, whichever occurs first. Logrank test will be used to determine the effect of YIV-906 on PFS
Secondary endpoints
• Secondary Objective: To determine the effect of YIV-906 on overall survival (OS). OS is
defined as the time between the date of randomization and the date of death due to any cause.
OS will be censored on the last date a patient is known to be alive.
• Secondary Objective: To determine the effect of YIV-906 on overall response rate (ORR).
Clinical response is defined as mRECIST partial or complete response. A logistic regression
model will be employed
• Secondary Objective: To determine the effect of YIV-906 on disease control rate (DCR).
Clinical response is defined as mRECIST partial or complete response. A logistic regression
model will be employed
• Secondary Objective: To determine the effect of YIV-906 on time to progression (TTP). The
analysis is similar to that of PFS
• Secondary Objective: To evaluate the effect of YIV-906 on quality of life associated with
sorafenib. Scores derived from the EORTC QLQ-C30 and QLQ-HCC18 will be analyzed by
means of linear regression analysis. Models will include factors for sorafenib and
comorbidity (Section 11.2)
• Adverse events as determined by CTCAE version 5, SAEs, discontinuation rate, dose
adjustment rate and tolerability of the combination
• Tumor response in terms of best overall response
• Sorafenib concentration after co-administration with YIV-906 at pre-dose (Cmin) and at 1
hour (C1h), 2 hours (C2h), 4 hours (C4h), 12 hours (C12h) post-dose
• To determine the effect of YIV-906 on progression-free survival (PFS). PFS
measured as time from randomization to progression according to RECIST 1.1 and mRECIST
(based on Investigator assessment) or death due to any cause, whichever occurs first. Logrank test will be used to determine the effect of YIV-906 on PFS
Secondary endpoints
• Secondary Objective: To determine the effect of YIV-906 on overall survival (OS). OS is
defined as the time between the date of randomization and the date of death due to any cause.
OS will be censored on the last date a patient is known to be alive.
• Secondary Objective: To determine the effect of YIV-906 on overall response rate (ORR).
Clinical response is defined as mRECIST partial or complete response. A logistic regression
model will be employed
• Secondary Objective: To determine the effect of YIV-906 on disease control rate (DCR).
Clinical response is defined as mRECIST partial or complete response. A logistic regression
model will be employed
• Secondary Objective: To determine the effect of YIV-906 on time to progression (TTP). The
analysis is similar to that of PFS
• Secondary Objective: To evaluate the effect of YIV-906 on quality of life associated with
sorafenib. Scores derived from the EORTC QLQ-C30 and QLQ-HCC18 will be analyzed by
means of linear regression analysis. Models will include factors for sorafenib and
comorbidity (Section 11.2)
• Adverse events as determined by CTCAE version 5, SAEs, discontinuation rate, dose
adjustment rate and tolerability of the combination
• Tumor response in terms of best overall response
• Sorafenib concentration after co-administration with YIV-906 at pre-dose (Cmin) and at 1
hour (C1h), 2 hours (C2h), 4 hours (C4h), 12 hours (C12h) post-dose
Inclution Criteria
• Male or females ≥18 years old with ability to take oral drugs
• Diagnosis of advanced HCC according to the American Association for the Study
of Liver Diseases (AASLD) Guidelines (Heimbach et al. 2018) or diagnosis by
tissue pathology
• Life expectancy of at least 3 months
• Presence of chronic hepatitis B (HBsAg (+), and IgM anti-HBc (-))
• Never received systemic antitumor therapy
• Patients must have at least one tumor lesion that meets both of the following
criteria:
o “Measurable disease according to mRECIST, i.e. at least one measurable
lesion.
o Advanced unresectable HCC that have liver limited disease who have
failed or not candidates to local therapies including surgery and localregional therapies; or patients with extrahepatic disease.
• Patients with an Eastern Cooperative Oncology Group (ECOG) performance
status ≤1
• Cirrhotic status of current Child-Pugh class A. Child-Pugh status should be
calculated based on clinical findings and laboratory results during the screening
period
• For patients with positive HBV-DNA and/or positive HBsAg results, they must
be treated with anti-HBV treatment (per local standard of care), as prophylaxis
starting at least 1-2 weeks prior to receiving study drug and willingness to continue
treatment for the length of the study
• Patients with adequate organ reserve, such as laboratory parameters:
o Absolute Neutrophil Count (ANC) ≥ 1.5 x 109
/L
o Platelets ≥ 60000 x 106
/L
o Hemoglobin (Hgb) ≥ 9 g/dL
o Serum alanine amino-transferase (ALT) ≤ 5 x ULN
• Adequate renal function, based upon meeting the following laboratory criteria
within 7 days before randomization:
o Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥
40mL/min (using the Cockroft-Gault equation: (140-age) x weight (kg)/
(serum creatinine x 72 [mg/dL] for males. (For females multiply by 0.85)
AND
o 24-hour urine protein <1 g
• Ability to understand and willingness to sign a written informed consent and to be
able to follow the visit schedule
• Diagnosis of advanced HCC according to the American Association for the Study
of Liver Diseases (AASLD) Guidelines (Heimbach et al. 2018) or diagnosis by
tissue pathology
• Life expectancy of at least 3 months
• Presence of chronic hepatitis B (HBsAg (+), and IgM anti-HBc (-))
• Never received systemic antitumor therapy
• Patients must have at least one tumor lesion that meets both of the following
criteria:
o “Measurable disease according to mRECIST, i.e. at least one measurable
lesion.
o Advanced unresectable HCC that have liver limited disease who have
failed or not candidates to local therapies including surgery and localregional therapies; or patients with extrahepatic disease.
• Patients with an Eastern Cooperative Oncology Group (ECOG) performance
status ≤1
• Cirrhotic status of current Child-Pugh class A. Child-Pugh status should be
calculated based on clinical findings and laboratory results during the screening
period
• For patients with positive HBV-DNA and/or positive HBsAg results, they must
be treated with anti-HBV treatment (per local standard of care), as prophylaxis
starting at least 1-2 weeks prior to receiving study drug and willingness to continue
treatment for the length of the study
• Patients with adequate organ reserve, such as laboratory parameters:
o Absolute Neutrophil Count (ANC) ≥ 1.5 x 109
/L
o Platelets ≥ 60000 x 106
/L
o Hemoglobin (Hgb) ≥ 9 g/dL
o Serum alanine amino-transferase (ALT) ≤ 5 x ULN
• Adequate renal function, based upon meeting the following laboratory criteria
within 7 days before randomization:
o Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥
40mL/min (using the Cockroft-Gault equation: (140-age) x weight (kg)/
(serum creatinine x 72 [mg/dL] for males. (For females multiply by 0.85)
AND
o 24-hour urine protein <1 g
• Ability to understand and willingness to sign a written informed consent and to be
able to follow the visit schedule
Exclusion Criteria
• Patients who ever have HCV infection
• Patients who have received systemic chemotherapies or immunotherapy or
molecular target therapies
• Patients who have received any local anti-cancer therapy within 4 weeks prior to
Cycle 1 treatment
• Active bleeding (including gastrointestinal bleeding, encephalopathy and ascites)
during the last 4 weeks prior to Cycle 1 treatment
• Patients with a history of allergy to the known components of YIV-906
• Known history of human immunodeficiency virus (HIV) seropositivity
• Known central nervous system metastasis including brain metastasis and
meningeal carcinomatosis
• Hepatocholangiocarcinoma, fibrolamellar cell carcinoma and mixed
hepatocellular carcinoma
• Active malignancy (except for definitively treated melanoma in-situ, basal or
squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix) within
the past 5 years
• Any severe and/or uncontrolled medical conditions including but not limiting:
o Unstable angina pectoris, symptomatic congestive heart failure,
myocardial infarction ≤ 6 months prior to Cycle 1 treatment, serious
uncontrolled cardiac arrhythmia, uncontrolled hypertension
o Previous transient ischemic attack (TIA), cerebral vascular accident
(CVA), symptomatic peripheral vascular disease (PVD) within last 6
months of Cycle 1 treatment
o Congenital long QT syndrome
o Alcoholic patients
o Acute and chronic, active infectious disorders and nonmalignant medical
illnesses that are uncontrolled or whose control may be jeopardized by the
complications of this study therapy, in the opinion of the investigator,
except chronic HBV
o Impairment of gastrointestinal function or who have gastrointestinal
disease that may significantly alter the absorption of study drugs (e.g.,
ulcerative disease, uncontrolled nausea, vomiting, diarrhea,
malabsorption syndrome)
o Patients who have had organ transplantation
• Patients receiving chronic treatment with corticosteroids (except for intermittent
topical or local injection of aldosterone) or another immunosuppressive agent
• Subjects receive any blood transfusion, albumin transfusion, erythropoietin
(EPO), granulocyte colony stimulating factor (G-CSF), TPO or other medical
supportive treatment prior to Cycle 1 treatment
• Patients treated with drugs known to be strong inducers of isoenzyme CYP3A
within 7 days of Cycle 1 treatment
• Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug
or who have not recovered from surgery
• Patients who have received an investigative drug or therapy within the last 4 weeks
prior to Cycle 1 treatment.
• Pregnant and/or breastfeeding women
• Men and women of childbearing age and potential, who are not willing to use
effective contraception
• Unwilling or unable to follow protocol requirements or to give informed consent
• Ongoing or recent history of autoimmune, uncontrolled psychiatric disorders and
drug abuse
• Uncontrolled hereditary or acquired thrombotic or bleeding disorder
• Bowel obstruction, history or presence of inflammatory enteropathy or extensive
intestinal resection
• Therapeutic dose anticoagulation with warfarin, or similar agents
• Chronic therapy with nonsteroidal anti-inflammatory agents or other anti-platelet
agents. Aspirin at doses up to 100 milligrams/day is permitted
• Patients with an estimated or calculated baseline creatinine clearance of less than
40 mL/min should not be enrolled in this trial
• No patient, however, may enroll in this trial if they are taking phenytoin (Dilantin)
• Patients taking traditional Chinese medicines within 14 days prior to taking first
dose of study treatment
• Patients who have received systemic chemotherapies or immunotherapy or
molecular target therapies
• Patients who have received any local anti-cancer therapy within 4 weeks prior to
Cycle 1 treatment
• Active bleeding (including gastrointestinal bleeding, encephalopathy and ascites)
during the last 4 weeks prior to Cycle 1 treatment
• Patients with a history of allergy to the known components of YIV-906
• Known history of human immunodeficiency virus (HIV) seropositivity
• Known central nervous system metastasis including brain metastasis and
meningeal carcinomatosis
• Hepatocholangiocarcinoma, fibrolamellar cell carcinoma and mixed
hepatocellular carcinoma
• Active malignancy (except for definitively treated melanoma in-situ, basal or
squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix) within
the past 5 years
• Any severe and/or uncontrolled medical conditions including but not limiting:
o Unstable angina pectoris, symptomatic congestive heart failure,
myocardial infarction ≤ 6 months prior to Cycle 1 treatment, serious
uncontrolled cardiac arrhythmia, uncontrolled hypertension
o Previous transient ischemic attack (TIA), cerebral vascular accident
(CVA), symptomatic peripheral vascular disease (PVD) within last 6
months of Cycle 1 treatment
o Congenital long QT syndrome
o Alcoholic patients
o Acute and chronic, active infectious disorders and nonmalignant medical
illnesses that are uncontrolled or whose control may be jeopardized by the
complications of this study therapy, in the opinion of the investigator,
except chronic HBV
o Impairment of gastrointestinal function or who have gastrointestinal
disease that may significantly alter the absorption of study drugs (e.g.,
ulcerative disease, uncontrolled nausea, vomiting, diarrhea,
malabsorption syndrome)
o Patients who have had organ transplantation
• Patients receiving chronic treatment with corticosteroids (except for intermittent
topical or local injection of aldosterone) or another immunosuppressive agent
• Subjects receive any blood transfusion, albumin transfusion, erythropoietin
(EPO), granulocyte colony stimulating factor (G-CSF), TPO or other medical
supportive treatment prior to Cycle 1 treatment
• Patients treated with drugs known to be strong inducers of isoenzyme CYP3A
within 7 days of Cycle 1 treatment
• Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug
or who have not recovered from surgery
• Patients who have received an investigative drug or therapy within the last 4 weeks
prior to Cycle 1 treatment.
• Pregnant and/or breastfeeding women
• Men and women of childbearing age and potential, who are not willing to use
effective contraception
• Unwilling or unable to follow protocol requirements or to give informed consent
• Ongoing or recent history of autoimmune, uncontrolled psychiatric disorders and
drug abuse
• Uncontrolled hereditary or acquired thrombotic or bleeding disorder
• Bowel obstruction, history or presence of inflammatory enteropathy or extensive
intestinal resection
• Therapeutic dose anticoagulation with warfarin, or similar agents
• Chronic therapy with nonsteroidal anti-inflammatory agents or other anti-platelet
agents. Aspirin at doses up to 100 milligrams/day is permitted
• Patients with an estimated or calculated baseline creatinine clearance of less than
40 mL/min should not be enrolled in this trial
• No patient, however, may enroll in this trial if they are taking phenytoin (Dilantin)
• Patients taking traditional Chinese medicines within 14 days prior to taking first
dose of study treatment
The Estimated Number of Participants
-
Taiwan
25 participants
-
Global
125 participants
