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

NCT02431312 | Completed Phase 1

• 1 other identifier: HBV-001
• Study Type: interventional
• Target: 90
• Locations: 8 countries
• Sites: 22

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.

Conditions

Hepatitis B

Keywords

Chronic HBV; immunotherapy; DNA vaccine; electroporation

Outcome Measures

Primary Outcomes (1)

• Safety Assessment (Composite of multiple measures: pain (VAS), adverse events, lab abnormalities, changes in vital signs)

  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 Outcomes (2)

• Immunogenicity Assessment

  Baseline (screening and first dose) and select points up to 76 weeks after the first dose

• Viral/Antiviral Assessment

  Screening and/or first dose and select points up to 76 weeks after the first dose

Other Outcomes (1)

• Exploratory Assessment

  Screening and/or first dose and select points up to 76 weeks after the first dose

Study Arms (6)

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.

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.

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.

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.

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.

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.

Drug: Nucleos(t)ide Analogue Treatment

Interventions

INO-1800 BIOLOGICAL

INO-1800 delivered by EP

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-9112 BIOLOGICAL

INO-9112 delivered by EP

Group B: high dose, standard regimen; Group B: mid dose, standard regimen

Nucleos(t)ide Analogue Treatment DRUG

Continued treatment with nucleos(t)ide analogue

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

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Inovio Pharmaceuticals: lead

Study Sites (22)

Research and Education, Inc.

San Diego, California, 92105, United States

Location

University of Miami Schiff Center for Liver Disease

Miami, Florida, 33136, United States

Location

Northwell Health

Manhasset, New York, 11030, United States

Location

Mount Sinai - PRIME

New York, New York, 10029, United States

Location

UC Physicians Company, LLC/Division of Digestive Diseases

Cincinnati, Ohio, 45267, United States

Location

Philadelphia VA Medical Center

Philadelphia, Pennsylvania, 19104, United States

Location

Harbourview Medical Center

Seattle, Washington, 98104, United States

Location

Nepean Hospital

Kingswood, New South Wales, 2747, Australia

Location

Mater Adult Hospital

South Brisbane, Queensland, 4101, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

The University of Hong Kong

Hong Kong, 00000, Hong Kong

Location

Auckland City Hospital

Auckland, 1023, New Zealand

Location

The Medical City

Pasig, 1605, Philippines

Location

Singapore General Hospital

Singapore, 169608, Singapore

Location

Chang Gung Memorial Hospital

Linkou District, Taoyuan County, 333, Taiwan

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 807, Taiwan

Location

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 112, Taiwan

Location

Siriraj Hospital, Mahidol University

Bangkoknoi, Bangkok, 10700, Thailand

Location

Maharaj Nakorn Chiang Mai Hospital

Tha Muang, Chiang Mai, 50200, Thailand

Location

Srinagarind Hospital

Khon Kaen, Muang District, 40002, Thailand

Location

MeSH Terms

Conditions

Hepatitis B

Interventions

rocakinogene sifuplasmid

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases

Study Officials

• ShuPing Yang, MD, PhD

  Inovio Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 21, 2015
• First Posted: May 1, 2015
• Study Start: January 12, 2015
• Primary Completion: May 22, 2018
• Study Completion: May 22, 2018
• Last Updated: October 15, 2019

Record last verified: 2019-10

Locations

PH (1); NZ (1); TH (3); HK (1); US (7); SG (1); AU (3); TW (5)