Hepatitis B Clinical Trial
Official 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
Verified date | October 2019 |
Source | Inovio Pharmaceuticals |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 90 |
Est. completion date | May 22, 2018 |
Est. primary completion date | May 22, 2018 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 65 Years |
Eligibility |
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) |
Country | Name | City | State |
---|---|---|---|
Australia | Royal Adelaide Hospital | Adelaide | South Australia |
Australia | Nepean Hospital | Kingswood | New South Wales |
Australia | Mater Adult Hospital | South Brisbane | Queensland |
Hong Kong | The University of Hong Kong | Hong Kong | |
New Zealand | Auckland City Hospital | Auckland | |
Philippines | The Medical City | Pasig City | |
Singapore | Singapore General Hospital | Singapore | |
Taiwan | Kaohsiung Medical University Chung-Ho Memorial Hospital | Kaohsiung | |
Taiwan | Chang Gung Memorial Hospital | Linkou | Taoyuan County |
Taiwan | Taichung Veterans General Hospital | Taichung | |
Taiwan | National Taiwan University Hospital | Taipei | |
Taiwan | Taipei Veterans General Hospital | Taipei | |
Thailand | Siriraj Hospital, Mahidol University | Bangkoknoi | Bangkok |
Thailand | Srinagarind Hospital | Khon Kaen | Muang District |
Thailand | Maharaj Nakorn Chiang Mai Hospital | Tha Muang | Chiang Mai |
United States | UC Physicians Company, LLC/Division of Digestive Diseases | Cincinnati | Ohio |
United States | Northwell Health | Manhasset | New York |
United States | University of Miami Schiff Center for Liver Disease | Miami | Florida |
United States | Mount Sinai - PRIME | New York | New York |
United States | Philadelphia VA Medical Center | Philadelphia | Pennsylvania |
United States | Research and Education, Inc. | San Diego | California |
United States | Harbourview Medical Center | Seattle | Washington |
Lead Sponsor | Collaborator |
---|---|
Inovio Pharmaceuticals |
United States, Australia, Hong Kong, New Zealand, Philippines, Singapore, Taiwan, Thailand,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Exploratory Assessment | Composite outcome measure consisting of multiple measures, including: Relationship between immunogenicity and antiviral response Expression of individual markers potentially predictive of immunogenic and antiviral responses |
Screening and/or first dose and select points up to 76 weeks after the first dose | |
Primary | Safety Assessment (Composite of multiple measures: pain (VAS), adverse events, lab abnormalities, changes in vital signs) | Composite outcome measure consisting of multiple measures, including: 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" Frequency and severity of local and systemic events for at least 7 days after Study Treatment/EP Frequency and severity of laboratory abnormalities Frequency and severity of all adverse events Changes in vital signs |
Signing of ICF through up to 76 weeks following the first dose | |
Secondary | Immunogenicity Assessment | Composite outcome measure consisting of multiple measures, including Breadth and Magnitude of antigen specific cellular immune responses Interferon-? ELISpot Flow Cytometry for T-cell activation, cytolytic phenotype, memory phenotype Breadth and Magnitude of antigen specific ELISA |
Baseline (screening and first dose) and select points up to 76 weeks after the first dose | |
Secondary | Viral/Antiviral Assessment | Composite outcome measure consisting of multiple measures, including: Evaluate effect on HBsAg kinetics as measured in the quantitative HBsAg assay Evaluate effect on maintenance of HBV DNA suppression (< 90 IU/ml) as measured in the quantitative viral load assay |
Screening and/or first dose and select points up to 76 weeks after the first dose |
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