Chronic Hepatitis, Hepatitis C Infection, Hepatocellular Carcinoma
Conditions
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.
Detailed description
PRIMARY OBJECTIVES: I. To determine the safety profile of the HCV DNA vaccine, consisting of INO-8000 (HCV antigen DNA) alone or co-administered with INO-9012 (interleukin \[IL\]-12 adjuvant DNA) (DNA plasmid encoding interleukin-12 INO-9012). II. To identify a dose of INO-9012 (IL-12 adjuvant DNA) for co-administration with INO-8000 (HCV antigen DNA) based on induction of HCV-specific interferon (IFN)-gamma production by peripheral blood mononuclear cells at 26 weeks compared to baseline in HCV-infected participants. TRANSLATIONAL OBJECTIVES: I. Determine the rate at which INO-8000 with different doses of INO-9012 induces a \> 1 log decrease (or undetectable) in HCV ribonucleic acid (RNA) level at weeks 14 and 26. II. Determine the rate at which INO-8000 with different doses of INO-9012 induces an end-of-treatment undetectable HCV RNA (end-of-treatment virologic response - EVR) at 26 weeks and a sustained virologic response (SVR) at 36 weeks. III. Determine the rate at which INO-8000 with different doses of INO-9012 induces other parameters of cluster of differentiation (CD)8 and CD4 T lymphocyte responses as measured by flow cytometry, and antibody responses to HCV antigen at weeks 14 and 26. OUTLINE: This is a dose-escalation study of INO-9012. Patients receive INO-8000 intramuscularly (IM) and DNA plasmid encoding interleukin-12 INO-9012 IM (dose levels 2-4) followed by electroporation (EP) at day 0 and at weeks 4, 12, and 24. After completion of study treatment, patients are followed up at weeks 48 and 76.
Interventions
BIOLOGICALElectroporation-Mediated Plasmid DNA Vaccine Therapy
Undergo electroporation
BIOLOGICALHCV DNA Vaccine INO-8000
Given IM
OTHERLaboratory Biomarker Analysis
Correlative studies
OTHERQuality-of-Life Assessment
Ancillary studies
BIOLOGICALRocakinogene Sifuplasmid
Given IM
Sponsors
National Cancer Institute (NCI)
Inovio Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* PRE-REGISTRATION INCLUSION CRITERIA * 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 * REGISTRATION INCLUSION CRITERIA * 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 * Screening laboratory values (serum chemistry, hematology, prothrombin time \[PT\](international normalized ratio \[INR\])/activated partial thromboplastin time \[APTT\], and creatine phosphokinase \[CPK\]) obtained up to 45 days prior to administration of first vaccine injection on day 0 within institutional normal range or judged to be not clinically significant by principal investigator (PI) and medical monitor * 12-lead electrocardiogram (ECG) showing normal heart rhythm; note: if there are abnormalities, then the abnormalities must be deemed of no clinical significance
Exclusion criteria
* PRE-REGISTRATION
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of dose-limiting toxicity | Baseline to 26 weeks | 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. |
| Mean change of interferon-gamma production by peripheral blood mononuclear cells | Baseline to 26 weeks | 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. |
Countries
Puerto Rico, United States
Contacts
PRINCIPAL_INVESTIGATORJeffrey M Jacobson
Mayo Clinic
Outcome results
None listed