phase i study of ino-1800 with or without ino-9112 + ep in chronic hepatitis b subjects

Conditions: Hepatitis B

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.


Eligibility 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)

Keywords: chronic hbv immunotherapy dna vaccine electroporation