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

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02431312
• Other study ID #: HBV-001
• Status: Completed
• Phase: Phase 1
• Start date: January 12, 2015
• Est. completion date: May 22, 2018

Study information

• Verified date: October 2019
• Source: Inovio Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• 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)

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic

Intervention

Biological:
• INO-1800
INO-1800 delivered by EP
• INO-9112
INO-9112 delivered by EP

Drug:
• Nucleos(t)ide Analogue Treatment
Continued treatment with nucleos(t)ide analogue

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Inovio Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Hong Kong,  New Zealand,  Philippines,  Singapore,  Taiwan,  Thailand, 

Outcome

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