CHRONVAC-C Study Followed by Standard of Care in Chronic Hepatitis C Virus (HCV) Subjects

Study Overview
=================
Brief Summary
-----------------
To explore the effect on early viral kinetics and viral load, and to determine safety, tolerability and anti-viral response for the plasmid DNA vaccine CHRONVAC-C administered i.m. in combination with electroporation followed by standard of care (SOC) in treatment naïve chronic HCV genotype 1 patients.

Official Title
-----------------
A Phase II Open-Label, Randomized, Parallel Group, Safety, Tolerability and Efficacy Study of i.m. Administered CHRONVAC-C in Combination With Electroporation Followed by Standard of Care in Chronic Hepatitis C Virus Genotype 1 Infected and Treatment Naïve Subjects

Conditions
-----------------
Chronic Hepatitis C

Intervention / Treatment
-----------------
* Drug: ChronVac-C + SOC
* Drug: SOC


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female subject 18 - 65 years of age with a known chronic hepatitis C infection, being treatment naїve (that is not being earlier treated for HCV infection) and a planned start of standard of care within 12 weeks from screening. Known genotype 1 infection. Viral load equal to 1000 IU/ml or more BMI less than 35. Considered probable that the deltoid muscles (left and right) of the subject will be reached at vaccination using a 12.7 mm cannula for injection and a 15 mm applicator tip for electroporation. Written informed consent obtained, and a copy provided to the subject. Subject legally competent and able to communicate effectively with the study personnel. Subject likely to co-operate and attend the clinic at the appointed times during the study Exclusion Criteria: Subject having clinically significant concomitant diseases other than HCV in the medical history to the discretion of the investigator. Subject having clinically significant findings on physical examination, vital signs, ECG or clinical laboratory evaluations to the discretion of the investigator. Subject having clinical or biochemical signs of cirrhosis. Positive hepatitis B surface antigen (HBsAg). Positive HIV antigen or antibody test. Subject having an ongoing and/or known viral infection other than HCV that requires treatment and/or special medical intention. Subject having received previous treatment for HCV. Radiation therapy or cytotoxic chemotherapeutic agents within 4 weeks prior to the first dose of study drug. Treatment with immunomodulating agents such as systemic corticosteroids, IL-2, IFN-alpha, IFN-beta, IFN-gamma within 4 weeks prior to the first dose of study drug. (Corticosteroid nasal sprays, inhaled steroids for asthma and/or topical steroids are allowed, however not on the vaccination area.) Immunization within 30 days of the first dose of the study drug. Subject having received an investigational drug product, or been enrolled in other investigational drug protocols within a period of 30 days prior to receiving the first dose of the study drug. Prior treatment with DNA therapy. Known allergy towards vaccines. Known allergy or contraindications to interferon and/or ribavirin or their excipients Known abuse of alcohol, drugs or pharmaceuticals. History, signs or symptoms of a cardiac disease. Presence of an implantable pacemaker. Any metal implants within the treatment areas (close to the right and/or left deltoid muscles). Diagnoses of a serious psychiatric illness which may influence study participation. Female subject who is pregnant or breast feeding. Female subject not clinically sterile (hysterectomy, tubal ligation or postmenopausal (amenorrhea > 1 year and FSH > 30 mU/ml) OR if not clinically sterile unwilling to use a reliable contraception method. Female subject with a positive urine pregnancy test. Male subject unwilling to use condom for active prevention of pregnancy from first vaccination to 4 months after last injection. Subject or their immediate families being an investigator or site personnel directly affiliated with this study. Immediate family is defined as a spouse, parent, child or sibling, whether biologically or legally adopted.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IMP_C/C IL28B<br>C/C IL28B subjects to whom IMP will be administrated prior to SOC | Drug: ChronVac-C + SOC<br>* IMP: I.m. administration of 500 μg plasmid DNA vaccine CHRONVAC-C (solution for injection) administered i.m. in combination with electroporation using MedPulser® DDS on 2 occasions with 4 weeks in between followed by standard of care (SOC) initiation after 14 - 42 days. SOC: Peg-IFN-α-2a (180 μg per week) and Ribavirin (1000 mg/day for subjects with a BW of < 75 kg and 1200 mg/day for subjects with a BW of > 75 kg)<br>|
| Active Comparator: SOC_C/C IL28B<br>C/C IL28B subjects to whom only SOC will be administrated | Drug: SOC<br>* SOC: Peg-IFN-α-2a (180 μg per week) and Ribavirin (1000 mg/day for subjects with a BW of < 75 kg and 1200 mg/day for subjects with a BW of > 75 kg)<br>|
| Experimental: IMP_non-C/C IL28B<br>non-C/C IL28B subjects to whom IMP will be administrated prior to SOC | Drug: ChronVac-C + SOC<br>* IMP: I.m. administration of 500 μg plasmid DNA vaccine CHRONVAC-C (solution for injection) administered i.m. in combination with electroporation using MedPulser® DDS on 2 occasions with 4 weeks in between followed by standard of care (SOC) initiation after 14 - 42 days. SOC: Peg-IFN-α-2a (180 μg per week) and Ribavirin (1000 mg/day for subjects with a BW of < 75 kg and 1200 mg/day for subjects with a BW of > 75 kg)<br>|
| Active Comparator: SOC_non-C/C IL28B<br>non-C/C IL28B subjects to whom only SOC will be administrated | Drug: SOC<br>* SOC: Peg-IFN-α-2a (180 μg per week) and Ribavirin (1000 mg/day for subjects with a BW of < 75 kg and 1200 mg/day for subjects with a BW of > 75 kg)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early viral kinetics - Second phase slope of viral decline |  | 0-4 weeks after SOC onset | 
| Rapid Viral Response (RVR). Percent subjects reaching non-detectable level of HCV-RNA. |  | 4 weeks after SOC onset | 
| Partial Early Viral Response (pEVR). Percent HCV-RNA positive subjects with more than 2 log 10 decline in HCV-RNA. |  | 12 weeks after SOC onset | 
| Complete Early Viral Response (cEVR). Percent subjects reaching non-detectable level of HCV-RNA. |  | 12 weeks after SOC onset | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local tolerance | Local tolerance will be measured for subjects randomized to vaccination. Local tolerance will be measured 3 times during a time period of 2 h post vaccination. The site of injection will also be inspected at the following visits. | up to 12 weeks after SOC onset | 
| Change from baseline in vital signs |  | 0 - 12 weeks | 
| Number of patients with AEs |  | 12 weeks | 
| Change of blood status from baseline |  | 0 - 12 weeks | 
| Exploratory Analysis - Characterization and quantification of the vaccine primed NS3-immune response |  | 0 - 12 weeks |