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

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

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.

Study Overview

• Status: Unknown
• Conditions: Chronic Hepatitis C
• Intervention / Treatment: Drug: ChronVac-C + SOC; Drug: SOC

• Study Type: Interventional
• Enrollment (Anticipated): 32
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ola RH Weiland, Professor; Phone Number: +46 (8) 585 800 00; Email: ola.weiland@ki.se

Study Locations

• Sweden
  • Huddinge, Sweden, SE-141 86
    • Recruiting
    • I73 Department of Infectious Diseases, Karolinska Institute, Karolinska University Hospital
    • Contact: Ola RH Weiland, Professor; Phone Number: +46 (8) 585 800 00; Email: ola.weiland@ki.se
    • Principal Investigator: Ola RH Weiland, Professor
  • Linköping, Sweden, SE-581 85
    • Recruiting
    • Division of Infectious Diseases, Department of Clinical and experimental medicine, Faculty of Health Sciences, Linköping University, Department of Infectious Diseases, County Council of Östergötland
    • Contact: Kristina Cardell, MD; Phone Number: +46 (0)10 103 00 00; Email: kristina.cardell@lio.se
    • Principal Investigator: Kristina Cardell, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IMP_C/C IL28B; C/C IL28B subjects to whom IMP will be administrated prior to SOC	Drug: ChronVac-C + SOC; 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)
Active Comparator: SOC_C/C IL28B; C/C IL28B subjects to whom only SOC will be administrated	Drug: SOC; 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)
Experimental: IMP_non-C/C IL28B; non-C/C IL28B subjects to whom IMP will be administrated prior to SOC	Drug: ChronVac-C + SOC; 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)
Active Comparator: SOC_non-C/C IL28B; non-C/C IL28B subjects to whom only SOC will be administrated	Drug: SOC; 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: ChronTech Pharma AB
• Collaborators: Inovio Pharmaceuticals
• Investigators: Principal Investigator: Ola RH Weiland, Professor, I73 Department of Infectious Diseases, Karolinska Institute, Karolinska University Hospital, Huddinge, Sweden; Study Chair: Anders G Vahlne, Professor, ChronTech Pharma AB, Hälsovägen 7, SE-141 57 Huddinge, Sweden; Study Director: Matti Sällberg, Professor, ChronTech Pharma AB, Hälsovägen 7, SE-141 57 Huddinge, Sweden

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Anticipated): June 1, 2012
• Study Completion (Anticipated): June 1, 2012

Study Registration Dates

• First Submitted: April 13, 2011
• First Submitted That Met QC Criteria: April 13, 2011
• First Posted (Estimate): April 14, 2011

Study Record Updates

• Last Update Posted (Estimate): October 12, 2011
• Last Update Submitted That Met QC Criteria: October 11, 2011
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis, Chronic; Hepatitis C, Chronic
• Other Study ID Numbers: CVC-202; 2010-022960-10 (EudraCT Number)