DNA Vaccine Therapy in Treating Patients With Chronic Hepatitis C Virus Infection

NCT02772003 | Active Not Recruiting Phase 1 DMC

• 6 other identifiers: NCI-2015-00558HHSN261201200042IN01-CN-2012-00042MAY2013-02-01N01CN00042P30CA015083
• Study Type: interventional
• Target: 33
• Locations: 2 countries
• Sites: 5

Brief Summary

This phase I trial studies the side effects and best dose of deoxyribonucleic acid (DNA) vaccine therapy in treating patients with hepatitis C virus (HCV) infection that persists or progresses over a long period of time. Vaccines made from DNA may help the body build an effective immune response to kill cancer cells that express HCV infection.

Conditions

Chronic Hepatitis; Hepatitis C Infection; Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (2)

• Incidence of dose-limiting toxicity

  Will be defined as an adverse event occurring after the initial vaccine administration, based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. The percentage of participants who experience grade 3 or worse adverse events and administration-site reactions following each dose will be summarized using descriptive statistics across each dose level.

  Baseline to 26 weeks

• Mean change of interferon-gamma production by peripheral blood mononuclear cells

  Change in production of interferon-gamma by peripheral blood mononuclear cells will be based on a one-way analysis of variance model using data from all dose levels at the 2-sided 5% level. Mean change (and % change) and the associated 95% confidence intervals in the production of IFN-gamma by peripheral blood mononuclear cells for all evaluable participants enrolled at each dose level will be computed, and compared across the dose levels in an exploratory fashion using graphical approaches, one-way analysis of variance models etc. to ascertain a dose-response curve.

  Baseline to 26 weeks

Other Outcomes (4)

• Percentage of participants with > 1 log decrease (or undetectable) in hepatitis C virus ribonucleic acid level

  Up to 26 weeks

• Percentage of participants with end-of-treatment undetectable hepatitis C virus ribonucleic acid for the dose levels determined to be safe

  26 weeks

• Sustained virologic response defined as undetectable hepatitis C virus ribonucleic acid

  36 weeks

Study Arms (1)

Treatment (INO-8000, INO-9012, EP)

EXPERIMENTAL

Patients receive INO-8000 IM and DNA plasmid encoding interleukin-12 INO-9012 IM (dose levels 2-4) followed by EP at day 0 and at weeks 4, 12, and 24.

Biological: Electroporation-Mediated Plasmid DNA Vaccine Therapy; Biological: HCV DNA Vaccine INO-8000; Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Biological: Rocakinogene Sifuplasmid

Interventions

Rocakinogene Sifuplasmid BIOLOGICAL

Given IM

Also known as: DNA Plasmid Encoding Interleukin-12 INO-9012, INO-9012

Treatment (INO-8000, INO-9012, EP)

Electroporation-Mediated Plasmid DNA Vaccine Therapy BIOLOGICAL

Undergo electroporation

Treatment (INO-8000, INO-9012, EP)

HCV DNA Vaccine INO-8000 BIOLOGICAL

Given IM

Also known as: INO-8000

Treatment (INO-8000, INO-9012, EP)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (INO-8000, INO-9012, EP)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (INO-8000, INO-9012, EP)

Eligibility Criteria

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

You may qualify if:

• Presence of active, chronic HCV infection confirmed by positive HCV RNA
• Willingness to use adequate contraception to avoid pregnancy or impregnation for the duration of study participation; Note:
• The effects of INO-8000 with or without INO-9012 on the developing human fetus at the recommended therapeutic dose are unknown; for this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
• 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 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
• Abstinence is only acceptable if it is in line with the preferred and usual lifestyle of the subject; periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of contraception
• Examples of contraceptive methods with an expected failure rate of \< 1% per year include male sterilization and hormonal implants; alternatively, proper use of combined oral or injected hormonal contraceptives and certain intrauterine devices or two methods (e.g., two barrier methods such as a condom and a cervical cap) may be combined to achieve a failure rate of \< 1% per year (barrier methods must always be supplemented with the use of a spermicide)
• Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
• Should a female partner of a male study participant become pregnant while the male participant is on study, the male participant should inform his study physician immediately
• Willingness to avoid excessive use of alcohol during the study; note: excessive use is defined as drinking \>= 8 alcoholic drinks per week on average
• Willingness to provide blood samples for research tests specified in the protocol
• Ability to understand and willingness to sign a written informed consent document
• Serum or plasma HCV RNA level \>= 10,000 IU/mL
• Screening HCV genotype, demonstrating genotype 1
• Alpha feto protein (AFP) levels within normal institutional limits or judged to be not clinically significant by the investigator; Exception: If deemed clinically significant, then liver imaging must be available within previous 6 months (e.g., ultrasound, computed tomography \[CT\] scan, magnetic resonance imaging \[MRI\]) showing no evidence of hepatocellular carcinoma
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1

You may not qualify if:

• Failure of previous HCV therapies
• Human immunodeficiency virus (HIV) infection
• Any previous treatment for HCV =\< 6 months prior to registration
• Other uncontrolled immune-compromising illness
• Autoimmune disorders, transplant recipients, other immunosuppression including any concurrent condition requiring the use of immunosuppressive/ immunomodulating agents; Exception: eye drop-containing and infrequent inhaled corticosteroids are permissible; topical corticosteroids are permissible at locations other than the administration site (upper arm); Note: All systemic corticosteroids must be discontinued at least 4 weeks prior to randomization; inhaled corticosteroids must be discontinued \>= 48 hours prior to randomization and courses of more than 2 weeks are not permissible within 4 weeks of randomization
• Ongoing hepatitis B virus (HBV) infection
• Documented evidence of fibrosis or cirrhosis (Metavir 2, 3, and 4) and subjects with significant extrahepatic manifestations of hepatitis C (such as cryoglobulinemia with symptoms or evidence of end-organ manifestations, renal disease, type 2 diabetes, or porphyria cutanea tarda
• Other known causes of significant liver disease including chronic or acute hepatitis B, acute hepatitis A, hemochromatosis, or homozygote alpha-1 antitrypsin deficiency
• Active malignancy; exception: non-melanoma skin cancers cancer(s) for which diagnosis and treatment was completed \>= 3 years prior to pre-registration
• History of major organ transplantation with an existing functional graft
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• History of cardiac arrhythmia, controlled or uncontrolled, including ventricular and supraventricular arrhythmia
• Pregnant or nursing women; Note: Pregnant women are excluded from this study because INO-8000 has an unknown potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with this DNA vaccine, breastfeeding should be discontinued if the mother is treated with INO-8000
• Current diagnosis or history of cardiac pre-excitation syndromes (e.g. Wolff-Parkinson-White)
• Metal implants on same limb as intended administration site

Sponsors & Collaborators

• National Cancer Institute (NCI): lead
• Inovio Pharmaceuticals: collaborator

Study Sites (5)

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

Temple University Hospital

Philadelphia, Pennsylvania, 19140, United States

Location

University of Puerto Rico

San Juan, 00936, Puerto Rico

Location

MeSH Terms

Conditions

Hepatitis, Chronic; Hepatitis C; Carcinoma, Hepatocellular

Interventions

rocakinogene sifuplasmid

Condition Hierarchy (Ancestors)

Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site

Study Officials

• Jeffrey M Jacobson

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2016
• First Posted: May 13, 2016
• Study Start: June 6, 2016
• Primary Completion: March 4, 2020
• Study Completion (Estimated): March 9, 2027
• Last Updated: April 13, 2026

Record last verified: 2026-03

Locations

PR (1); US (4)