Hepatitis BPhase 1NCT02431312
Phase I Study of INO-1800 With or Without INO-9112 + EP in Chronic Hepatitis B Subjects
A Phase 1 study testing INO-1800, INO-9112 and Nucleos(t)ide Analogue Treatment in people with Hepatitis B, run by Inovio Pharmaceuticals at 22 sites in 8 countries.
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… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hepatitis B
- What is being tested?
- INO-1800, INO-9112 and Nucleos(t)ide Analogue Treatment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 22 sitesin 8 countries
- Study dates
- 12 Jan 2015to 22 May 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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)
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- 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)
Trial locations and contacts
22 sites in 8 countries.
22 sites in 8 countries
United States7 sites
UC Physicians Company, LLC/Division of Digestive Diseases
Cincinnati, Ohio, 45267
Northwell Health
Manhasset, New York, 11030
University of Miami Schiff Center for Liver Disease
Miami, Florida, 33136
Mount Sinai - PRIME
New York, New York, 10029
Philadelphia VA Medical Center
Philadelphia, Pennsylvania, 19104
Research and Education, Inc.
San Diego, California, 92105
Harbourview Medical Center
Seattle, Washington, 98104
Taiwan5 sites
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung City, 807
Chang Gung Memorial Hospital
Linkou District, Taoyuan County, 333
Taichung Veterans General Hospital
Taichung, 40705
National Taiwan University Hospital
Taipei, 10002
Taipei Veterans General Hospital
Taipei, 112
Australia3 sites
Royal Adelaide Hospital
Adelaide, South Australia, 5000
Nepean Hospital
Kingswood, New South Wales, 2747
Mater Adult Hospital
South Brisbane, Queensland, 4101
Thailand3 sites
Siriraj Hospital, Mahidol University
Bangkoknoi, Bangkok, 10700
Srinagarind Hospital
Khon Kaen, Muang District, 40002
Maharaj Nakorn Chiang Mai Hospital
Tha Muang, Chiang Mai, 50200
About this study
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
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.
- Conditions
- Hepatitis B
- Being tested
- INO-1800, INO-9112, Nucleos(t)ide Analogue Treatment
- Keywords
- Chronic HBV, immunotherapy, DNA vaccine, electroporation
- Medical subject headings
- Hepatitis B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
INO-1800Biological
INO-1800 delivered by EP
INO-9112Biological
INO-9112 delivered by EP
Nucleos(t)ide Analogue TreatmentDrug
Continued treatment with nucleos(t)ide analogue
| Study group | Role | What they receive |
|---|---|---|
| Group A: low dose, standard regimen | Experimental | 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. Receives: Biological: INO-1800; Drug: Nucleos(t)ide Analogue Treatment |
| Group A: mid dose, standard regimen | Experimental | 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. Receives: Biological: INO-1800; Drug: Nucleos(t)ide Analogue Treatment |
| Group A: high dose, standard regimen | Experimental | 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. Receives: Biological: INO-1800; Drug: Nucleos(t)ide Analogue Treatment |
| Group B: mid dose, standard regimen | Experimental | 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. Receives: Biological: INO-1800; Biological: INO-9112; Drug: Nucleos(t)ide Analogue Treatment |
| Group B: high dose, standard regimen | Experimental | 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. Receives: Biological: INO-1800; Biological: INO-9112; Drug: Nucleos(t)ide Analogue Treatment |
| Active Control: nucleos(t)ide analogue treatment | Active comparator | Participants continued treatment with nucleos(t)ide analogue treatment. Receives: Drug: Nucleos(t)ide Analogue Treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Signing of ICF through up to 76 weeks following the first dose
Secondary outcomes (2)
Immunogenicity Assessment
Composite outcome measure consisting of multiple measures, including
- Breadth and Magnitude of antigen specific cellular immune responses
- Interferon-ɣ ELISpot
- Flow Cytometry for T-cell activation, cytolytic phenotype, memory phenotype
- Breadth and Magnitude of antigen specific ELISA
Measured: Baseline (screening and first dose) and select points up to 76 weeks after the first dose
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
Measured: Screening and/or first dose and select points up to 76 weeks after the first dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2015 (estimated)
- Study start12 Jan 2015
- Primary completion22 May 2018
- Study completion22 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatitis BStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- Inovio Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- ShuPing Yang, MD, PhD, Study director, Inovio Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02431312
- Sponsor's protocol ID
- HBV-001
- Status last verified
- Oct 2019
- First submitted
- 21 Apr 2015
- Last updated
- 15 Oct 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02431312
- Acronym / sponsor ID
- HBV-001
- Conditions
- Hepatitis B
- Keywords
- Chronic HBV, immunotherapy, DNA vaccine, electroporation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- Inovio PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 12 Jan 2015 (actual)
- Primary completion
- 22 May 2018 (actual)
- Study completion
- 22 May 2018 (actual)
- First posted
- 1 May 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Group A: low dose, standard regimen | Experimental | Biological: INO-1800, Drug: Nucleos(t)ide Analogue TreatmentParticipants 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. |
| Group A: mid dose, standard regimen | Experimental | Biological: INO-1800, Drug: Nucleos(t)ide Analogue TreatmentParticipants 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. |
| Group A: high dose, standard regimen | Experimental | Biological: INO-1800, Drug: Nucleos(t)ide Analogue TreatmentParticipants 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. |
| Group B: mid dose, standard regimen | Experimental | Biological: INO-1800, Biological: INO-9112, Drug: Nucleos(t)ide Analogue TreatmentParticipants 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. |
| Group B: high dose, standard regimen | Experimental | Biological: INO-1800, Biological: INO-9112, Drug: Nucleos(t)ide Analogue TreatmentParticipants 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. |
| Active Control: nucleos(t)ide analogue treatment | Active comparator | Drug: Nucleos(t)ide Analogue TreatmentParticipants continued treatment with nucleos(t)ide analogue treatment. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (17 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| INO-1800INO-1800 delivered by EP | Biological | Group A: high dose, standard regimen, Group A: low dose, standard regimen, Group A: mid dose, standard regimen, Group B: high dose, standard regimen, Group B: mid dose, standard regimen |
| INO-9112INO-9112 delivered by EP | Biological | Group B: high dose, standard regimen, Group B: mid dose, standard regimen |
| Nucleos(t)ide Analogue TreatmentContinued treatment with nucleos(t)ide analogue | Drug | Active Control: nucleos(t)ide analogue treatment, Group A: high dose, standard regimen, Group A: low dose, standard regimen, Group A: mid dose, standard regimen, Group B: high dose, standard regimen, Group B: mid dose, standard regimen |
Primary outcome
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
2 secondary outcomes
Immunogenicity Assessment
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
ShuPing Yang, MD, PhD study director
Inovio Pharmaceuticals
22 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing INO-1800, INO-9112 and Nucleos(t)ide Analogue Treatment in people with Hepatitis B, run by Inovio Pharmaceuticals at 22 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in United States, Taiwan, Australia, Thailand, Hong Kong and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2019.