Clinical Trials List
Protocol NumberHBV-001
NCT Number(ClinicalTrials.gov Identfier)NCT02431312
2015-08-01 - 2017-12-31
Phase I
Terminated5
ICD-10B18
Chronic viral hepatitis
Phase I, Randomized, Open-Label, Active-Controlled, Dose Escalation Study To evaluate The Safety, Tolerability, And Immunogenicity Of INO-1800 Alone Or in Combination With INO-9112 Delivered IM Followed By Electroporation In Select Nucleos(t)ide Analogue-Treated, HBeAG-Positive, Chronic Hepatitis B Patients
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Trial Applicant
IQVIA RDS Taiwan Ltd.
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Sponsor
Inovio Pharmaceuticals, Inc.
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 王苑貞 Digestive System Department
- I-Cheng Lee Digestive System Department
- Chien-Wei Su Digestive System Department
- 林漢傑 Digestive System Department
- 黃惠君 Digestive System Department
- 藍耿欣 Digestive System Department
The Actual Total Number of Participants Enrolled
2 Stop recruiting
Audit
None
Co-Principal Investigator
- Yi-Cheng Chen Digestive System Department
- Chen-Chun Lin Digestive System Department
- Chau-Ting Yeh Digestive System Department
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- Ming-Lung Yu Digestive System Department
- Jee-Fu Huang Digestive System Department
- 黃駿逸 Digestive System Department
- Ming-Lun Yeh Digestive System Department
- Chia-Yen Dai Digestive System Department
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 楊宏志 Digestive System Department
- Chun-Jen Liu Digestive System Department
- 蘇東弘 Digestive System Department
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Condition/Disease
Chronic Hepatitis B
Objectives
Primary Objective:
Evaluate the safety and tolerability of escalating doses of INO-1800, alone or in combination
with INO-9112 in two different regimens, when delivered intramuscularly followed by EP in
ETV- and/or TDF-treated subjects with chronic Hepatitis B virus infection
Primary Safety Endpoints:
Incidence of adverse events classified by system organ class (SOC), preferred term (PT),
severity, and relationship to Study Treatment and schedule
Administration (injection) site reactions (described by frequency and severity grade) and VAS
scores for administration site pain
Changes in safety laboratory parameters described by frequency and severity grade (e.g., liver
panel, vital signs, and ECGs)
Secondary Objectives:
Evaluate the cellular and humoral immune response to INO-1800, alone or in combination
with INO-9112 in two different regimens, when delivered intramuscularly followed by EP in
ETV- and/or TDF-treated subjects with chronic Hepatitis B virus infection
Evaluate effect of INO-1800, alone or in combination with INO-9112, on HBsAg kinetics and
other viral and antiviral parameters when delivered intramuscularly followed by EP in ETVand/or TDF-treated subjects with chronic Hepatitis B virus infection
Test Drug
INO-1800 and INO-9112
Active Ingredient
INO-1800 : Plasmids pGX1802, pGX1803 and pGX1806
INO-9112 : The plasmid pGX6010
INO-9112 : The plasmid pGX6010
Dosage Form
0.4 mL minimum/vial (2 mL glass vial)
Dosage
10.0 mg/ml combined
9.6 mg/ml
9.6 mg/ml
Endpoints
2. Safety:
Safety Assessment: Subjects will be monitored for:
1. Local pain immediately after Study Treatment/EP and at select times using a visual analog
scale (VAS)
2. Local and systemic events for 7 days after Study Treatment/EP as noted on the Participant
Reminder Diary
3. Laboratory abnormalities (e.g., liver panel, CBC, hematology, PT(INR), serum chemistry,
CPK, urinalysis, ECG)
4. All Adverse events
5. Vital Signs
Immunogenicity Assessment:
This study will explore humoral and cell mediated immune responses to INO-1800 alone or in
combination with INO-9112 at screening, prior to the first dose, and at select visits according to
the schedule outlined in the Schedule of Events and described in Study Procedures and Treatments
(Section 6).
Viral/Antiviral Assessment:
Changes in quantitative HBsAg, HBV DNA, qualitative HBsAg and qualitative HBeAg, HBsAg
loss, HBeAg loss for HBeAg positive subjects, anti-HBs and anti-HBe levels (anti-HBe for
HBeAg positive subjects), and maintenance of HBeAg negative status for HBeAg negative
subjects will be evaluated according to the schedule outlined in the Schedule of Events and
described in Study Procedures and Treatments (Section 6).
Exploratory Assessment:
Markers and panels potentially predictive of immunogenicity and antiviral activity, such as HBV
genotype by serology or through documentation, HBsAg/anti-HBs complex levels and
comprehensive gene expression profiles, will be evaluated according to the schedule outlined in
the Schedule of Events and described in Study Procedures and Treatments (Section 6).
Additionally, results obtained from the qualitative HBeAg assessment will be applied to determine
semi-quantitative concentrations of HBeAg for research purposes only. The relationship between
cellular and humoral immune responses and HLA type will be explored for each subject. Finally,
immunogenicity and antiviral activity as it relates to HBeAg status and nucleos(t)ide analogue
treatment duration will be explored.
Safety Assessment: Subjects will be monitored for:
1. Local pain immediately after Study Treatment/EP and at select times using a visual analog
scale (VAS)
2. Local and systemic events for 7 days after Study Treatment/EP as noted on the Participant
Reminder Diary
3. Laboratory abnormalities (e.g., liver panel, CBC, hematology, PT(INR), serum chemistry,
CPK, urinalysis, ECG)
4. All Adverse events
5. Vital Signs
Immunogenicity Assessment:
This study will explore humoral and cell mediated immune responses to INO-1800 alone or in
combination with INO-9112 at screening, prior to the first dose, and at select visits according to
the schedule outlined in the Schedule of Events and described in Study Procedures and Treatments
(Section 6).
Viral/Antiviral Assessment:
Changes in quantitative HBsAg, HBV DNA, qualitative HBsAg and qualitative HBeAg, HBsAg
loss, HBeAg loss for HBeAg positive subjects, anti-HBs and anti-HBe levels (anti-HBe for
HBeAg positive subjects), and maintenance of HBeAg negative status for HBeAg negative
subjects will be evaluated according to the schedule outlined in the Schedule of Events and
described in Study Procedures and Treatments (Section 6).
Exploratory Assessment:
Markers and panels potentially predictive of immunogenicity and antiviral activity, such as HBV
genotype by serology or through documentation, HBsAg/anti-HBs complex levels and
comprehensive gene expression profiles, will be evaluated according to the schedule outlined in
the Schedule of Events and described in Study Procedures and Treatments (Section 6).
Additionally, results obtained from the qualitative HBeAg assessment will be applied to determine
semi-quantitative concentrations of HBeAg for research purposes only. The relationship between
cellular and humoral immune responses and HLA type will be explored for each subject. Finally,
immunogenicity and antiviral activity as it relates to HBeAg status and nucleos(t)ide analogue
treatment duration will be explored.
Inclution Criteria
a. Male and female subjects 18-65 years of age, inclusive; (Taiwan will only recruit subjects
equal or older than 20 years old.)
b. Chronic Hepatitis B virus infection;
c. Negative serological tests for Hepatitis A IgM, Hepatitis C, Hepatitis D and human immunodeficiency virus (HIV);
d. Liver biopsy, Fibroscan® or equivalent elastography-based test obtained within the past 6 months demonstrating liver disease consistent with chronic hepatitis B without evidence of significant bridging fibrosis, defined as absence of Metavir ≥ F3 with a recommended cutoff of 8.5 kPA for Fibroscan®, or cirrhosis, supported by platelet count greater than the central
laboratory LLN at screening;
e. Positive test for Hepatitis B surface antigen for at least 6 months prior to randomization;
f. HBsAg titer ≥ 250 IU/mL at screening;
g. Any nucleos(t)ide analogue treatment for at least 1 year with ongoing entecavir and/or
tenofovir treatment at randomization and 3 months prior to randomization;
h. HBV DNA < 90 IU/mL for at least the preceding 6 months;
i. HBV DNA < 90 IU/mL at screening;
j. Screening laboratory values (CBC, serum chemistry, CPK, urinalysis, ECG, PT(INR)/PTT)
obtained up to 30 days prior to first Study Treatment within normal range or judged to be
not clinically significant by PI and medical monitor;
k. ALT ≤ 1.5x ULN from 2 measurements separated by at least 14 days during the 6 months
prior to randomization (one of the ALT measurements can be done at screening);
l. ALT at screening ≤ 1.5x ULN;
m.AST, TBili, DBili, GT, Alk Phos and albumin within normal range or judged to be not
clinically significant by PI and medical monitor at screening;
n. For men and women who are not postmenopausal [i.e., ≥ 12 months of non-therapy-induced
amenorrhea, confirmed by follicle stimulating hormone (FSH), if not on hormone
replacement] or surgically sterile (vasectomy in males or absence of ovaries and/or uterus in
females), agreement to remain abstinent or use one highly effective or combined
contraceptive methods that result in a failure rate of < 1% per year during the treatment
period and at least through week 12 after last dose.
• Abstinence is only acceptable if it is in line with the preferred and usual lifestyle of the
subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or
post-ovulation methods) and withdrawal are not acceptable methods of contraception;
• Examples of contraceptive methods with an expected failure rate of < 1% per year
include male sterilization and hormonal implants. Alternatively, proper use of
combined oral or injected hormonal contraceptives and certain intrauterine devices or
two methods (e.g., two barrier methods such as a condom and a cervical cap) may be
combined to achieve a failure rate of < 1% per year (barrier methods must always be
supplemented with the use of a spermicide);
o. Ability and willingness of subject to provide written informed consent.
equal or older than 20 years old.)
b. Chronic Hepatitis B virus infection;
c. Negative serological tests for Hepatitis A IgM, Hepatitis C, Hepatitis D and human immunodeficiency virus (HIV);
d. Liver biopsy, Fibroscan® or equivalent elastography-based test obtained within the past 6 months demonstrating liver disease consistent with chronic hepatitis B without evidence of significant bridging fibrosis, defined as absence of Metavir ≥ F3 with a recommended cutoff of 8.5 kPA for Fibroscan®, or cirrhosis, supported by platelet count greater than the central
laboratory LLN at screening;
e. Positive test for Hepatitis B surface antigen for at least 6 months prior to randomization;
f. HBsAg titer ≥ 250 IU/mL at screening;
g. Any nucleos(t)ide analogue treatment for at least 1 year with ongoing entecavir and/or
tenofovir treatment at randomization and 3 months prior to randomization;
h. HBV DNA < 90 IU/mL for at least the preceding 6 months;
i. HBV DNA < 90 IU/mL at screening;
j. Screening laboratory values (CBC, serum chemistry, CPK, urinalysis, ECG, PT(INR)/PTT)
obtained up to 30 days prior to first Study Treatment within normal range or judged to be
not clinically significant by PI and medical monitor;
k. ALT ≤ 1.5x ULN from 2 measurements separated by at least 14 days during the 6 months
prior to randomization (one of the ALT measurements can be done at screening);
l. ALT at screening ≤ 1.5x ULN;
m.AST, TBili, DBili, GT, Alk Phos and albumin within normal range or judged to be not
clinically significant by PI and medical monitor at screening;
n. For men and women who are not postmenopausal [i.e., ≥ 12 months of non-therapy-induced
amenorrhea, confirmed by follicle stimulating hormone (FSH), if not on hormone
replacement] or surgically sterile (vasectomy in males or absence of ovaries and/or uterus in
females), agreement to remain abstinent or use one highly effective or combined
contraceptive methods that result in a failure rate of < 1% per year during the treatment
period and at least through week 12 after last dose.
• Abstinence is only acceptable if it is in line with the preferred and usual lifestyle of the
subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or
post-ovulation methods) and withdrawal are not acceptable methods of contraception;
• Examples of contraceptive methods with an expected failure rate of < 1% per year
include male sterilization and hormonal implants. Alternatively, proper use of
combined oral or injected hormonal contraceptives and certain intrauterine devices or
two methods (e.g., two barrier methods such as a condom and a cervical cap) may be
combined to achieve a failure rate of < 1% per year (barrier methods must always be
supplemented with the use of a spermicide);
o. Ability and willingness of subject to provide written informed consent.
Exclusion Criteria
a. Female subjects who are pregnant or breastfeeding;
b. Positive serum pregnancy test during screening or positive urine pregnancy test at
randomization;
c. Use of topical corticosteroids at or near the intended administration site (topical
corticosteroids permissible at locations other than upper arm);
d. Autoimmune disorders, transplant recipients, other immunosuppression including any
concurrent condition requiring the use of immunosuppressive/ immunomodulating agents
(eye drop-containing and infrequent inhaled corticosteroids are permissible).
• Systemic corticosteroids that are not discontinued at least 4 weeks prior to randomization;
• More than three courses of inhaled corticosteroids of no more than 14 consecutive days
each within 6 months of randomization, and if any course is not discontinued one week prior to randomization;
e. Expected need for systemic antiviral treatment (other than ETV and/or TDF);
f. Documented history or other evidence of decompensated liver disease (e.g., ascites,
bleeding from esophageal varices, Child-Pugh clinical classification B or C);
g. History of liver cirrhosis demonstrated by biopsy or Fibroscan®
or equivalent
elastography-based test;
h. History of other evidence of a medical condition associated with chronic liver disease
[e.g., hemochromatosis, autoimmune hepatitis, alcoholic liver disease, non-alcoholic
steatohepatitis (NASH), toxin exposure, thalassemia, etc.];
i. Documented history or other evidence of metabolic liver disease within one year of
randomization;
j. Abnormal renal function including serum creatinine > ULN or calculated creatinine
clearance < 70 mL/min (using the Cockcroft Gault formula);
k. History of or suspicion of hepatocellular carcinoma;
l. Screening alpha fetoprotein greater than or equal to 13 ng/mL;
m. Prior history or current malignancy other than adequately treated basal cell carcinoma
(BCC), unless the history of BCC is near the intended site of treatment administration;
n. History of significant medical conditions [e.g., cardiac (including ventricular or
supraventricular arrhythmias), renal disease, pulmonary, gastrointestinal, neurological];
o. Significant acute infection (e.g., influenza, local infection) or any other clinically
significant illness within 2 weeks of randomization;
p. Administration of any blood product within 3 months of randomization;
q. Participation in a study with an investigational compound or device within 30 days of
randomization;
r. History of seizures (unless seizure free for 5 years);
s. Less than two acceptable sites exist for intramuscular injection and EP between use of the
deltoid and lateral quadriceps muscles. A site for injection/EP is not acceptable if there are
tattoos or scars within 2 cm of the injection/EP site or if there is implanted metal within
the same limb. Any device implanted in the chest (e.g., cardiac pacemaker or defibrillator)
excludes the use of the deltoid muscle on the same side of the body;
t. History (within 3 months of randomization) of alcohol consumption exceeding 2 standard
drinks per day on average (1 standard drink = 10-15 grams of alcohol, refer to Appendix
E) and/or drug use;
u. Prisoners or individuals who are compulsorily detained (involuntarily incarcerated) for
treatment of either a psychiatric or physical (e.g., infectious disease) illness;
v. Any other conditions, including history of significant psychiatric disease, judged by the
Investigator that would limit the evaluation of a subject.
b. Positive serum pregnancy test during screening or positive urine pregnancy test at
randomization;
c. Use of topical corticosteroids at or near the intended administration site (topical
corticosteroids permissible at locations other than upper arm);
d. Autoimmune disorders, transplant recipients, other immunosuppression including any
concurrent condition requiring the use of immunosuppressive/ immunomodulating agents
(eye drop-containing and infrequent inhaled corticosteroids are permissible).
• Systemic corticosteroids that are not discontinued at least 4 weeks prior to randomization;
• More than three courses of inhaled corticosteroids of no more than 14 consecutive days
each within 6 months of randomization, and if any course is not discontinued one week prior to randomization;
e. Expected need for systemic antiviral treatment (other than ETV and/or TDF);
f. Documented history or other evidence of decompensated liver disease (e.g., ascites,
bleeding from esophageal varices, Child-Pugh clinical classification B or C);
g. History of liver cirrhosis demonstrated by biopsy or Fibroscan®
or equivalent
elastography-based test;
h. History of other evidence of a medical condition associated with chronic liver disease
[e.g., hemochromatosis, autoimmune hepatitis, alcoholic liver disease, non-alcoholic
steatohepatitis (NASH), toxin exposure, thalassemia, etc.];
i. Documented history or other evidence of metabolic liver disease within one year of
randomization;
j. Abnormal renal function including serum creatinine > ULN or calculated creatinine
clearance < 70 mL/min (using the Cockcroft Gault formula);
k. History of or suspicion of hepatocellular carcinoma;
l. Screening alpha fetoprotein greater than or equal to 13 ng/mL;
m. Prior history or current malignancy other than adequately treated basal cell carcinoma
(BCC), unless the history of BCC is near the intended site of treatment administration;
n. History of significant medical conditions [e.g., cardiac (including ventricular or
supraventricular arrhythmias), renal disease, pulmonary, gastrointestinal, neurological];
o. Significant acute infection (e.g., influenza, local infection) or any other clinically
significant illness within 2 weeks of randomization;
p. Administration of any blood product within 3 months of randomization;
q. Participation in a study with an investigational compound or device within 30 days of
randomization;
r. History of seizures (unless seizure free for 5 years);
s. Less than two acceptable sites exist for intramuscular injection and EP between use of the
deltoid and lateral quadriceps muscles. A site for injection/EP is not acceptable if there are
tattoos or scars within 2 cm of the injection/EP site or if there is implanted metal within
the same limb. Any device implanted in the chest (e.g., cardiac pacemaker or defibrillator)
excludes the use of the deltoid muscle on the same side of the body;
t. History (within 3 months of randomization) of alcohol consumption exceeding 2 standard
drinks per day on average (1 standard drink = 10-15 grams of alcohol, refer to Appendix
E) and/or drug use;
u. Prisoners or individuals who are compulsorily detained (involuntarily incarcerated) for
treatment of either a psychiatric or physical (e.g., infectious disease) illness;
v. Any other conditions, including history of significant psychiatric disease, judged by the
Investigator that would limit the evaluation of a subject.
The Estimated Number of Participants
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Taiwan
30 participants
-
Global
126 participants
