TG4040 in Patients With Chronic HCV

NCT00449124 | Withdrawn Phase 1

• 1 other identifier: 05-0061
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to evaluate the safety and effectiveness of an investigational vaccine (TG4040) to prevent hepatitis C virus (HCV) infection. The primary goal of this study is to determine the safety of increasing doses of TG4040 versus placebo (an inactive substance) in subjects chronically infected with HCV. Approximately 85 patients, ages 18-65 years, with chronic HCV infection will be enrolled in this study at two sites, Saint Louis University and Cincinnati Children's Hospital. Volunteers will receive doses of TG4040 and placebo by injections into the thigh on different days, depending on which study group they belong to. Safety will be checked before doses are increased, and each participant will receive the study vaccine, TG4040, at some point during the study. Each subject will participate in the study for 8 months. This study may help produce a new vaccine that would improve control of HCV.

Conditions

Hepatitis C

Keywords

hepatitis C, vaccine, TG4040

Outcome Measures

Primary Outcomes (2)

• Part I and Part II: safety including measures of reactogenicity, changes in blood counts and hepatic panel.

  Solicited reactogenicity and AEs will be collected on the day of vaccination and daily for 6 days following vaccination. Unsolicited AEs will be collected throughout the study period.

• Part II: change in serum levels of HCV RNA compared to baseline.

  Part I: screening days -60 and -30, days 0, 14, 28 and month 6. Part II: screening days -60 and -30, days 0, 14, 28, 56, 90, and 180.

Secondary Outcomes (1)

• Tests to assess immunogenicity of the vaccine candidate and include, but are not limited to, development of anti-HCV using standard commercial assays and research assays, developed of enhanced in vitro T cell reactivity when stimulated with HCV antigens.

  Part I: time points 1, 2, and 3-days 0, 7 and 14 post-vaccination and 2 months following the 3rd vaccination. Part II: time points 1 and 2-days 0, 7 and 14 post vaccination and 1, 2, 3 and 6 months following the 2nd vaccination.

Study Arms (7)

Part I-group 1

EXPERIMENTAL

Part I/Group 1: Cycle 1-TG4040 10\^6 PFU days 0, 7 and 14; Cycle 2-Placebo days 0, 7 and 14; Cycle 3-Placebo days 0, 7 and 14.

Drug: Placebo; Biological: TG4040

Part IIa-group 1

EXPERIMENTAL

Part IIa/Group 1: Cycle 1-TG4040 10\^8 PFU days 0, 7 and 14; Cycle 2-Placebo days 0, 7 and 14.

Drug: Placebo; Biological: TG4040

Part IIa-group 2

EXPERIMENTAL

Part IIa/Group 2: Cycle 1-Placebo days 0, 7 and 14; Cycle 2-TG4040 10\^8 PFU days 0, 7 and 14.

Drug: Placebo; Biological: TG4040

Part I-group 3

EXPERIMENTAL

Part I/Group 3: Cycle 1-Placebo days 0, 7 and 14; Cycle 2-Placebo days 0, 7 and 14; Cycle 3-TG4040 10\^8 PFU days 0, 7 and 14.

Drug: Placebo; Biological: TG4040

Part I-group 2

EXPERIMENTAL

Part I/Group 2: Cycle 1-Placebo days 0, 7 and 14; Cycle 2-TG4040 10\^7 PFU days 0, 7 and 14; Cycle 3-Placebo days 0, 7 and 14.

Drug: Placebo; Biological: TG4040

Part IIb-group 1

EXPERIMENTAL

Part IIb/Group 1: Cycle 1-TG4040 10\^8 PFU days 0, 7 and 14; Cycle 2-Placebo days 0, 7 and 14.

Drug: Placebo; Biological: TG4040

Part IIb-group 2

EXPERIMENTAL

Part IIa/Group 2: Cycle 1-Placebo days 0, 7 and 14; Cycle 2-TG4040 10\^8 PFU days 0, 7 and 14.

Drug: Placebo; Biological: TG4040

Interventions

Placebo DRUG

Injections of 0.5 mL of normal saline solution (0.9% NaCl).

Part I-group 1; Part I-group 2; Part I-group 3; Part IIa-group 1; Part IIa-group 2; Part IIb-group 1; Part IIb-group 2

TG4040 BIOLOGICAL

Modified vaccinia virus Ankara encoding hepatitis C virus (HCV) proteins NS3, NS4, and NS5B administered by subcutaneous injection into the thigh. Dosages: TG4040 10\^6 PFU, TG4040 10\^7 PFU and TG4040 10\^8 PFU.

Part I-group 1; Part I-group 2; Part I-group 3; Part IIa-group 1; Part IIa-group 2; Part IIb-group 1; Part IIb-group 2

Eligibility Criteria

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

You may qualify if:

• Part I and Part II:
• Informed consent obtained and signed;
• Male or female patients, age 18-65 years old (inclusive)
• Female patients will be menopausal for at least 12 months, surgically sterile or agree not to become pregnant from the time of study enrollment until at least 28 days after the administration of vaccine or placebo. A woman is considered of childbearing potential unless post-menopausal or surgically sterilized.
• If the volunteer is female, of childbearing potential, and sexually active, she agrees to use acceptable contraception. (Acceptable contraception methods are restricted to effective intrauterine devices (IUDs) or licensed hormonal products with use of method for a minimum of 30 days prior to vaccination and for the entire study period post-vaccination).
• Note: A woman is eligible if she is monogamous with a vasectomized male or abstinent, without the additional need for hormonal or barrier birth control methods upon review of a reproductive history.
• With chronic hepatitis C evidenced by:
• HCV RNA detectable in blood, and
• A liver biopsy compatible with chronic hepatitis C;
• Infected with HCV genotype 1;
• Non-cirrhotic patients, i.e. liver biopsy available within one year prior to baseline, excluding stage 4 fibrosis; otherwise, if no liver biopsy of less than one year is available, it will be performed at baseline;
• Patients participating in:
• Part I will be non-responder patients: patients having received at least 3 months of pegylated IFN-alpha (IFN-alpha) plus ribavirin, with currently detectable HCV RNA (whether or not they reach, Early Virologic Response (EVR, defined as a reduction of HCV RNA by at least 2 logs from baseline or negative at 12 weeks) and/or SVR) with \> 6 months between the end of PEG IFN-alpha treatment and the first TG4040 injection;
• Part IIa will be either non-responder or relapser patients. Part IIb will be treatment-naïve patients: patients who have never received IFN-based treatment
• Patients must have compensated liver disease, defined through use of the Child-Pugh scoring system with:

You may not qualify if:

• Part I and Part II:
• Co-infection with HBV (indicated by the presence of hepatitis B surface antigen (HBsAg) in serum) or HIV (anti-HIV in serum); patients with HIV positive sexual partner (by history) will not be included;
• Current HCV therapies through out the trial period
• Current alcohol abuse or drug addiction that in the opinion of the investigator may interfere with the subject's ability to comply with trial procedures.
• History of immunodeficiency
• Known or suspected impairment of immunologic function including moderate to severe kidney impairment
• Malignancy within the last 5 years, not including squamous cell skin cancer or basal cell skin cancer unless at the vaccination site or history of skin cancer at the vaccination site
• Significant cardiac disease, evidenced by:
• History of myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, chest pain or shortness of breath on activity, or other heart conditions under the care of a physician
• Baseline ECG showing clinically significant abnormalities (e.g., all kinds of advanced atrioventricular block or intraventricular block with QRS \>120msec, QTc \>460 msec, or frequent premature atrial contractions, atrial fibrillation or other atrial arrhythmias, \> ventricular couplets or ST-T wave abnormalities diagnostic of myocardial ischemia or prior myocardial infarction. EKGs will be interpreted by an identified cardiologist at Saint Louis University prior to enrollment.
• Baseline echocardiogram showing clinically significant abnormalities including valvular disease or contractile dysfunction.
• Ten percent or greater risk of developing a myocardial infarction or coronary death within the next 10 years using the National Cholesterol Education Program's risk assessment tool (http://hin.nhlbi.nih.gov/atpiii/calculator.asp)
• NOTE: This criterion applies only to subjects 20 years of age and older AND only if at least one of the following apply:
• A) have smoked a cigarette in the past month, and/or B) have hypertension (defined as systolic blood pressure \>140 mm Hg) or are on antihypertensive medication, and/or C) have a family history of coronary heart disease in male first-degree relative (father or brother) \< 55 years of age or a female first-degree relative (mother or sister) \< 65 years of age.
• Current use of immunosuppressive medication; Corticosteroid nasal sprays, Inhaled steroids for asthma and/or topical steroids are permissible. Persons taking short courses of oral steroids for conditions such as poison ivy will need to wait a period of 2 weeks after completion of the steroids to begin vaccination.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (2)

Saint Louis University

St Louis, Missouri, 63110-0250, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

MeSH Terms

Conditions

Hepatitis C

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NIH

Study Record Dates

• First Submitted: March 15, 2007
• First Posted: March 19, 2007
• Primary Completion: September 1, 2007
• Study Completion: September 1, 2007
• Last Updated: January 23, 2019

Record last verified: 2008-06

Locations

US (2)