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

October 11, 2019 updated by: Inovio Pharmaceuticals

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
90

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Kingswood, New South Wales, Australia, 2747
        • Nepean Hospital
    • Queensland
      • South Brisbane, Queensland, Australia, 4101
        • Mater Adult Hospital
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Royal Adelaide Hospital
  • Hong Kong
      • Hong Kong, Hong Kong, 00000
        • The University of Hong Kong
  • New Zealand
      • Auckland, New Zealand, 1023
        • Auckland City Hospital
  • Philippines
      • Pasig City, Philippines, 1605
        • The Medical City
  • Singapore
      • Singapore, Singapore, 169608
        • Singapore General Hospital
  • Taiwan
      • Kaohsiung, Taiwan, 807
        • Kaohsiung Medical University Chung-Ho Memorial Hospital
      • Taichung, Taiwan, 40705
        • Taichung Veterans General Hospital
      • Taipei, Taiwan, 10002
        • National Taiwan University Hospital
      • Taipei, Taiwan, 112
        • Taipei Veterans General Hospital
    • Taoyuan County
      • Linkou, Taoyuan County, Taiwan, 333
        • Chang Gung Memorial Hospital
  • Thailand
    • Bangkok
      • Bangkoknoi, Bangkok, Thailand, 10700
        • Siriraj Hospital, Mahidol University
    • Chiang Mai
      • Tha Muang, Chiang Mai, Thailand, 50200
        • Maharaj Nakorn Chiang Mai Hospital
    • Muang District
      • Khon Kaen, Muang District, Thailand, 40002
        • Srinagarind Hospital
  • United States
    • California
      • San Diego, California, United States, 92105
        • Research and Education, Inc.
    • Florida
      • Miami, Florida, United States, 33136
        • University of Miami Schiff Center for Liver Disease
    • New York
      • Manhasset, New York, United States, 11030
        • Northwell Health
      • New York, New York, United States, 10029
        • Mount Sinai - PRIME
    • Ohio
      • Cincinnati, Ohio, United States, 45267
        • UC Physicians Company, LLC/Division of Digestive Diseases
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Philadelphia VA Medical Center
    • Washington
      • Seattle, Washington, United States, 98104
        • Harbourview Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 61 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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
Drug: Nucleos(t)ide Analogue Treatment
Continued treatment with nucleos(t)ide analogue
Biological: INO-9112
INO-9112 delivered by EP
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
Drug: Nucleos(t)ide Analogue Treatment
Continued treatment with nucleos(t)ide analogue
Biological: INO-9112
INO-9112 delivered by EP
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
Signing of ICF through up to 76 weeks following the first dose

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
Baseline (screening and first dose) and select points up to 76 weeks after the first dose
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
Screening and/or first dose and select points up to 76 weeks after the first dose

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
Screening and/or first dose and select points up to 76 weeks after the first dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Inovio Pharmaceuticals

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: ShuPing Yang, MD, PhD, Inovio Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 12, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 22, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 22, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 21, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 30, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 1, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 15, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 11, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • HBV-001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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