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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02431312




Registration number
NCT02431312
Ethics application status
Date submitted
21/04/2015
Date registered
1/05/2015
Date last updated
15/10/2019

Titles & IDs
Public title
Phase I Study of INO-1800 With or Without INO-9112 + EP in Chronic Hepatitis B Subjects
Scientific title
Phase I, Randomized, Open-Label, Active-Controlled, Dose Escalation Study to Evaluate the Safety, Tolerability & Immunogenicity of INO-1800 Alone or in Combination With INO-9112 Delivered IM Followed by EP in Select Nucleos(t)Ide Analogue-Treated, Chronic Hepatitis B Patients
Secondary ID [1] 0 0
HBV-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis B 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - INO-1800
Other interventions - INO-9112
Treatment: Drugs - Nucleos(t)ide Analogue Treatment

Experimental: Group A: low dose, standard regimen - Participants received 3 or 4 doses of 0.3 mg INO-1800 delivered by EP in a standard regimen while continuing treatment with nucleos(t)ide analogue treatment.

Experimental: Group A: mid dose, standard regimen - Participants received 3 or 4 doses of 2 mg INO-1800 delivered by EP in a standard regimen while continuing treatment with nucleos(t)ide analogue treatment.

Experimental: Group A: high dose, standard regimen - Participants received 3 or 4 doses of 9 mg INO-1800 delivered by EP in a standard regimen while continuing treatment with nucleos(t)ide analogue treatment.

Experimental: Group B: mid dose, standard regimen - Participants received 3 or 4 doses of 2 mg INO-1800 + 0.25 mg INO-9112 delivered by EP in a standard regimen while continuing treatment with nucleos(t)ide analogue treatment.

Experimental: Group B: high dose, standard regimen - Participants received 3 or 4 doses of 9 mg INO-1800 + 0.25 mg INO-9112 delivered by EP in a standard regimen while continuing treatment with nucleos(t)ide analogue treatment.

Active Comparator: Active Control: nucleos(t)ide analogue treatment - Participants continued treatment with nucleos(t)ide analogue treatment.


Other interventions: INO-1800
INO-1800 delivered by EP

Other interventions: INO-9112
INO-9112 delivered by EP

Treatment: Drugs: Nucleos(t)ide Analogue Treatment
Continued treatment with nucleos(t)ide analogue
Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety Assessment (Composite of multiple measures: pain (VAS), adverse events, lab abnormalities, changes in vital signs)
Timepoint [1] 0 0
Signing of ICF through up to 76 weeks following the first dose
Secondary outcome [1] 0 0
Immunogenicity Assessment
Timepoint [1] 0 0
Baseline (screening and first dose) and select points up to 76 weeks after the first dose
Secondary outcome [2] 0 0
Viral/Antiviral Assessment
Timepoint [2] 0 0
Screening and/or first dose and select points up to 76 weeks after the first dose

Eligibility
Key inclusion criteria
INCLUSION CRITERIA:

- Chronic Hepatitis B virus infection

- Negative for Hepatitis A IgM, C, D and HIV

- Liver biopsy, Fibroscan® or equivalent elastography-based test obtained within the
past 6 months demonstrating liver disease without evidence of bridging fibrosis or
cirrhosis supported by platelet count greater than the central laboratory LLN at
screening

- Positive for Hepatitis B surface antigen (=250 IU/mL at screening)

- Nucleos(t)ide treatment for at least 1 year with ongoing nucleos(t)ide analogue
treatment at randomization

- HBV DNA <90 IU/mL for =6 months prior to randomization

- Screening laboratory values within normal range

- ALT =1.5x upper limit of normal (ULN) from 2 measurements separated by at least 14
days during the 6 months prior to randomization and ALT at screening =1.5x ULN

- AST, TBili, DBili, GGT, Alk Phos and albumin within normal range or judged to be not
clinically significant by PI and medical monitor at screening

- 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 1 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

EXCLUSION CRITERIA:

- Pregnant or breastfeeding females

- Positive serum pregnancy test at screening or positive urine pregnancy test at
randomization

- Use of topical corticosteroids at or near the intended administration site

- 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)

- Need for systemic antiviral treatment (other than for chronic hepatitis B infection)

- Documented history or other evidence of decompensated liver disease (e.g., ascites,
bleeding from esophageal varices, Child-Pugh clinical classification B or C)

- History of liver cirrhosis demonstrated by biopsy, Fibroscan® or equivalent
elastography-based test

- 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.]

- Documented history or other evidence of metabolic liver disease within 1yr of
randomization

- Abnormal renal function including serum creatinine >ULN or calculated creatinine
clearance <70 mL/min (using the Cockcroft Gault formula)

- History of or suspicion of HCC

- Screening alpha fetoprotein =13 ng/mL

- Prior history or current malignancy other than adequately treated BCC, unless history
of BCC is near intended administration site

- History of significant medical conditions [e.g., cardiac (including ventricular or
supraventricular arrhythmias), renal disease, pulmonary, gastrointestinal,
neurological]

- Significant acute infection (e.g., influenza, local infection) or any other clinically
significant illness within 2 weeks of randomization

- Administration of any blood product within 3 mon of randomization

- History of seizures (unless seizure free for 5yrs)
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Factorial
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/01/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
22/05/2018
Sample size
Target
Accrual to date
Final
90
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA
Recruitment hospital [1] 0 0
Nepean Hospital - Kingswood
Recruitment hospital [2] 0 0
Mater Adult Hospital - South Brisbane
Recruitment hospital [3] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 0 0
2747 - Kingswood
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
Ohio
Country [5] 0 0
United States of America
State/province [5] 0 0
Pennsylvania
Country [6] 0 0
United States of America
State/province [6] 0 0
Washington
Country [7] 0 0
Hong Kong
State/province [7] 0 0
Hong Kong
Country [8] 0 0
New Zealand
State/province [8] 0 0
Auckland
Country [9] 0 0
Philippines
State/province [9] 0 0
Pasig City
Country [10] 0 0
Singapore
State/province [10] 0 0
Singapore
Country [11] 0 0
Taiwan
State/province [11] 0 0
Taoyuan County
Country [12] 0 0
Taiwan
State/province [12] 0 0
Kaohsiung
Country [13] 0 0
Taiwan
State/province [13] 0 0
Taichung
Country [14] 0 0
Taiwan
State/province [14] 0 0
Taipei
Country [15] 0 0
Thailand
State/province [15] 0 0
Bangkok
Country [16] 0 0
Thailand
State/province [16] 0 0
Chiang Mai
Country [17] 0 0
Thailand
State/province [17] 0 0
Muang District

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Inovio Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This was an open-label study that evaluated the safety, tolerability, and immunogenicity of
dose combinations of INO-1800 (DNA plasmids encoding Hepatitis B surface antigen [HBsAg] and
Hepatitis B core antigen [HBcAg]) and INO-9112 (DNA plasmid encoding human interleukin 12)
delivered by electroporation (EP) in 90 (ninety) nucleos(t)ide analogue treated participants.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02431312
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
ShuPing Yang, MD, PhD
Address 0 0
Inovio Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02431312