Clinical trial NCT02431312: Phase I Study of INO-1800 With or Without INO-9112 + EP in Chronic Hepatitis B Subjects
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatitis B
Keywords: Chronic HBV
immunotherapy
DNA vaccine
electroporation
Lead sponsor: Inovio Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2015-05-01
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.


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)

Primary outcomes:
measure: Safety Assessment (Composite of multiple measures: pain (VAS), adverse events, lab abnormalities, changes in vital signs)
timeFrame: Signing of ICF through up to 76 weeks following the first dose
Secondary outcomes:
measure: Immunogenicity Assessment
timeFrame: Baseline (screening and first dose) and select points up to 76 weeks after the first dose
measure: Viral/Antiviral Assessment
timeFrame: Screening and/or first dose and select points up to 76 weeks after the first dose
Other outcomes:
measure: Exploratory Assessment
timeFrame: Screening and/or first dose and select points up to 76 weeks after the first dose
Locations:
city: San Diego
country: United States
facility: Research and Education, Inc.
state: California
city: Miami
country: United States
facility: University of Miami Schiff Center for Liver Disease
state: Florida
city: Manhasset
country: United States
facility: Northwell Health
state: New York
city: New York
country: United States
facility: Mount Sinai - PRIME
state: New York
city: Cincinnati
country: United States
facility: UC Physicians Company, LLC/Division of Digestive Diseases
state: Ohio
city: Philadelphia
country: United States
facility: Philadelphia VA Medical Center
state: Pennsylvania
city: Seattle
country: United States
facility: Harbourview Medical Center
state: Washington
city: Kingswood
country: Australia
facility: Nepean Hospital
state: New South Wales
city: South Brisbane
country: Australia
facility: Mater Adult Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Hong Kong
country: Hong Kong
facility: The University of Hong Kong
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Pasig City
country: Philippines
facility: The Medical City
city: Singapore
country: Singapore
facility: Singapore General Hospital
city: Linkou
country: Taiwan
facility: Chang Gung Memorial Hospital
state: Taoyuan County
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Bangkoknoi
country: Thailand
facility: Siriraj Hospital, Mahidol University
state: Bangkok
city: Tha Muang
country: Thailand
facility: Maharaj Nakorn Chiang Mai Hospital
state: Chiang Mai
city: Khon Kaen
country: Thailand
facility: Srinagarind Hospital
state: Muang District
Study officials:
affiliation: Inovio Pharmaceuticals
name: ShuPing Yang, MD, PhD
role: STUDY_DIRECTOR
References: