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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02431312
Recruitment Status : Completed
First Posted : May 1, 2015
Last Update Posted : October 15, 2019
Sponsor:
Information provided by (Responsible Party):
Inovio Pharmaceuticals

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.

Condition or disease Intervention/treatment Phase
Hepatitis B Biological: INO-1800 Biological: INO-9112 Drug: Nucleos(t)ide Analogue Treatment Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : January 12, 2015
Actual Primary Completion Date : May 22, 2018
Actual Study Completion Date : May 22, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Group A: low dose, standard regimen
Participants received 3 or 4 doses of 0.3 mg INO-1800 delivered by EP in a standard regimen while continuing treatment with nucleos(t)ide analogue treatment.
Biological: INO-1800
INO-1800 delivered by EP

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

Experimental: Group A: mid dose, standard regimen
Participants received 3 or 4 doses of 2 mg INO-1800 delivered by EP in a standard regimen while continuing treatment with nucleos(t)ide analogue treatment.
Biological: INO-1800
INO-1800 delivered by EP

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

Experimental: Group A: high dose, standard regimen
Participants received 3 or 4 doses of 9 mg INO-1800 delivered by EP in a standard regimen while continuing treatment with nucleos(t)ide analogue treatment.
Biological: INO-1800
INO-1800 delivered by EP

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

Experimental: Group B: mid dose, standard regimen
Participants received 3 or 4 doses of 2 mg INO-1800 + 0.25 mg INO-9112 delivered by EP in a standard regimen while continuing treatment with nucleos(t)ide analogue treatment.
Biological: INO-1800
INO-1800 delivered by EP

Biological: INO-9112
INO-9112 delivered by EP

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

Experimental: Group B: high dose, standard regimen
Participants received 3 or 4 doses of 9 mg INO-1800 + 0.25 mg INO-9112 delivered by EP in a standard regimen while continuing treatment with nucleos(t)ide analogue treatment.
Biological: INO-1800
INO-1800 delivered by EP

Biological: INO-9112
INO-9112 delivered by EP

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

Active Comparator: Active Control: nucleos(t)ide analogue treatment
Participants continued treatment with nucleos(t)ide analogue treatment.
Drug: Nucleos(t)ide Analogue Treatment
Continued treatment with nucleos(t)ide analogue




Primary Outcome Measures :
  1. Safety Assessment (Composite of multiple measures: pain (VAS), adverse events, lab abnormalities, changes in vital signs) [ Time Frame: Signing of ICF through up to 76 weeks following the first dose ]

    Composite outcome measure consisting of multiple measures, including:

    1. 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"
    2. Frequency and severity of local and systemic events for at least 7 days after Study Treatment/EP
    3. Frequency and severity of laboratory abnormalities
    4. Frequency and severity of all adverse events
    5. Changes in vital signs


Secondary Outcome Measures :
  1. Immunogenicity Assessment [ Time Frame: Baseline (screening and first dose) and select points up to 76 weeks after the first dose ]

    Composite outcome measure consisting of multiple measures, including

    1. Breadth and Magnitude of antigen specific cellular immune responses

      • Interferon-ɣ ELISpot
      • Flow Cytometry for T-cell activation, cytolytic phenotype, memory phenotype
    2. Breadth and Magnitude of antigen specific ELISA

  2. Viral/Antiviral Assessment [ Time Frame: Screening and/or first dose and select points up to 76 weeks after the first dose ]

    Composite outcome measure consisting of multiple measures, including:

    1. Evaluate effect on HBsAg kinetics as measured in the quantitative HBsAg assay
    2. Evaluate effect on maintenance of HBV DNA suppression (< 90 IU/ml) as measured in the quantitative viral load assay


Other Outcome Measures:
  1. Exploratory Assessment [ Time Frame: Screening and/or first dose and select points up to 76 weeks after the first dose ]

    Composite outcome measure consisting of multiple measures, including:

    1. Relationship between immunogenicity and antiviral response
    2. Expression of individual markers potentially predictive of immunogenic and antiviral responses



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02431312


Locations
Show Show 22 study locations
Sponsors and Collaborators
Inovio Pharmaceuticals
Investigators
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Study Director: ShuPing Yang, MD, PhD Inovio Pharmaceuticals
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Responsible Party: Inovio Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02431312    
Other Study ID Numbers: HBV-001
First Posted: May 1, 2015    Key Record Dates
Last Update Posted: October 15, 2019
Last Verified: October 2019
Keywords provided by Inovio Pharmaceuticals:
Chronic HBV
immunotherapy
DNA vaccine
electroporation
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Hepatitis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Infections
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Blood-Borne Infections
Communicable Diseases
Hepadnaviridae Infections
DNA Virus Infections
Hepatitis, Chronic