Hepatitis B
Conditions
Keywords
Chronic HBV, immunotherapy, DNA vaccine, electroporation
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.
Interventions
BIOLOGICALINO-1800
INO-1800 delivered by EP
BIOLOGICALINO-9112
INO-9112 delivered by EP
Continued treatment with nucleos(t)ide analogue
Sponsors
Inovio Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety Assessment (Composite of multiple measures: pain (VAS), adverse events, lab abnormalities, changes in vital signs) | Signing of ICF through up to 76 weeks following the first dose | Composite outcome measure consisting of multiple measures, including: 1. Local pain immediately after Study Treatment/EP and at select times using a visual analog scale (VAS) from 0 to 10, with 0 representing No Pain and 10 representing Worst Pain 2. Frequency and severity of local and systemic events for at least 7 days after Study Treatment/EP 3. Frequency and severity of laboratory abnormalities 4. Frequency and severity of all adverse events 5. Changes in vital signs |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity Assessment | Baseline (screening and first dose) and select points up to 76 weeks after the first dose | Composite outcome measure consisting of multiple measures, including 1. Breadth and Magnitude of antigen specific cellular immune responses * Interferon-ɣ ELISpot * Flow Cytometry for T-cell activation, cytolytic phenotype, memory phenotype 2. Breadth and Magnitude of antigen specific ELISA |
| Viral/Antiviral Assessment | Screening and/or first dose and select points up to 76 weeks after the first dose | Composite outcome measure consisting of multiple measures, including: 1. Evaluate effect on HBsAg kinetics as measured in the quantitative HBsAg assay 2. Evaluate effect on maintenance of HBV DNA suppression (\< 90 IU/ml) as measured in the quantitative viral load assay |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory Assessment | Screening and/or first dose and select points up to 76 weeks after the first dose | Composite outcome measure consisting of multiple measures, including: 1. Relationship between immunogenicity and antiviral response 2. Expression of individual markers potentially predictive of immunogenic and antiviral responses |
Countries
Australia, Hong Kong, New Zealand, Philippines, Singapore, Taiwan, Thailand, United States
Outcome results
None listed