Phase I Study of INO-1800 With or Without INO-9112 + EP in Chronic Hepatitis B Subjects

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

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.

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)