Staged Phase I/II Hepatitis C Prophylactic Vaccine

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01436357
First received: September 15, 2011
Last updated: September 25, 2014
Last verified: July 2014
  Purpose

Phase I/II, double-blinded, randomized, placebo-controlled study of HCV-uninfected male and female active IDU aged 18 to 45 years. In Stage I 68 (+/-4) evaluable subjects will be enrolled and then an interim analysis of safety data will be performed. In Stage II an additional 276 (+/-4) subjects will be enrolled.


Condition Intervention Phase
Hepatitis C
Other: Placebo
Biological: MVA-NSmut
Biological: AdCh3NSmut1
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Staged Phase I/II Study, to Assess Safety, Efficacy and Immunogenicity of a New Hepatitis C Prophylactic Vaccine Based on Sequential Use of AdCh3NSmut1 and MVA-NSmut

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Incidence of chronic hepatitis C virus (HCV) infection at 6 months defined by persistent viremia over a period of 6 months after initial detection of primary infection. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Occurrence of vaccine-related serious adverse events (SAEs) from the time of first vaccination through the entire study period, per treatment arm. [ Time Frame: Day 0 to 29 months ] [ Designated as safety issue: Yes ]
  • Occurrence of severe local and/or systemic solicited reactogenicity signs and symptoms in the 8 days (Day 0-7) after each vaccination, per treatment arm. [ Time Frame: Day 0 to 7 ] [ Designated as safety issue: Yes ]
  • Occurrence of clinical safety laboratory adverse events (AEs) assessed at baseline and 1 month following each vaccination, per treatment arm. [ Time Frame: Day 0 to 1 month ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Frequency of positive cell mediated immune response by treatment group (vaccine vs. placebo) measured by interferon gamma (IFN-gamma) production by T-cells in response to at least one out of the six HCV genotype 1b peptide pools in the vaccine. [ Time Frame: Within 14 days after the last vaccination (Day 56) ] [ Designated as safety issue: No ]

Estimated Enrollment: 352
Study Start Date: March 2012
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (Stage I and II)
Receive AdCh3NSmut1 at 2.5 x 10^10 total virus particles (vp)/dose at day 0 followed by 1 dose of MVA-NSmut intramuscularly 56 days later at the dosage 1.8 x10^8 plaque forming units (pfu): 34 (+/-2) subjects Stage I, then 138 (+/-2) subjects at Stage II.
Biological: MVA-NSmut
Stages I and II: 1 dose of MVA-NSmut at the dosage 1.8 x10^8 plaque forming units (pfu) intramuscularly on day 56.
Biological: AdCh3NSmut1
Stages I and II: Receive AdCh3NSmut1 at 2.5 x 10^10 total virus particles (vp)/dose, intramuscularly on day 0.
Placebo Comparator: Arm B (Stage I and II)
Two doses of placebo intramuscularly, 1 at day 0 and 1 at day 56: 34 (+/-2) subjects Stage I, then 138 (+/-2) subjects at Stage II.
Other: Placebo
Stages I and II: Two doses of placebo intramuscularly, 1 at day 0 and 1 at day 56.

Detailed Description:

A two stage, Phase I/II, double-blinded, randomized, placebo-controlled study of hepatitis C virus (HCV)uninfected male and female injection drug users (IDU) aged 18 to 45. In this clinical trial AdCh3NSmut1 and MVA-NSMut HCV vaccine will be administered intramuscularly to 68 (+/-4) evaluable volunteers. A planned interim analysis of safety and immunogenicity will be conducted based on data through 1 week after receipt of the second vaccination. If no safety signal is detected and there is evidence of a measurable immune response to HCV then an additional 276 (+/-4) volunteers will be enrolled.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Comprehension of informed consent.
  • 18-45 year old men or women with acknowledged active IDU in the past 90 days and have no travel plans that would interfere with ability to meet the study visit schedule.
  • In good general health as determined by a participating study physician and results within acceptable ranges for clinical laboratory evaluations as detailed in Appendix A.
  • Negative for antibodies to hepatitis C virus (anti-HCV).
  • Negative for HCV RNA.
  • Negative antibodies to HIV.
  • Negative for HBsAg.
  • Able and willing (in the Investigator's opinion) to comply with all study requirements.
  • Willing to allow the investigators access to their medical records.
  • Willingness to practice continuous effective contraception from the screening visit through 90 days after the last vaccination (males and females).
  • Among females, a negative pregnancy test within 24 hours prior to vaccination.
  • Agreement to refrain from blood donation during the course of the study or after the study.
  • Provide written informed consent prior to initiation of any study procedures.
  • Willing to provide contact information for study follow-up activities, including the address, name and contact information of three people who can be contacted to facilitate follow-up compliance.

Exclusion Criteria:

  • The subject is currently participating in a study that involves an experimental agent (vaccine, drug, biologic device, blood product, or medication) or has received an experimental agent within 30 days prior to enrollment in this study, or expects to receive another experimental agent during participation in this study.
  • Prior receipt of a recombinant simian or human adenoviral vaccine or MVA vaccine.
  • Administration of immunoglobulins and/or any blood products within the 90 days preceding the planned administration of the vaccine candidate.
  • Any confirmed or suspected immunosuppressive or immunodeficient state, including: HIV infection; asplenia; recurrent, severe infections.
  • History of allergic disease or reactions likely to be exacerbated by any component of the vaccine (i.e., known hypersensitivity to aminoglycosideantibiotics or to egg proteins).
  • History of clinically significant contact dermatitis or other significant dermatological conditions such as psoriasis.
  • Any history of anaphylaxis in reaction to vaccination.
  • Pregnancy, lactation or willingness/intention to become pregnant during the study.
  • History of cancer (except for successfully treated basal cell carcinoma of the skin and cervical carcinoma in situ).
  • History of severe psychiatric illness, including severe depression, history of suicidal ideation, suicidal attempts, or psychosis requiring medication. The subject has a diagnosis of schizophrenia, bi-polar disease, or other severe (disabling) chronic psychiatric diagnosis that is uncontrolled and would interfere with the ability to adhere to the protocol.
  • Any other serious chronic illness requiring hospital specialist supervision.
  • Suspected or known current alcohol abuse as defined by a score of 10 or more on the Alcohol Use Disorders Identification Test (AUDIT) C test (a standardized screening tool used to identify hazardous drinkers or those with active alcohol use disorders, including abuse or dependence).
  • At high risk of HIV infection by the following criteria (adapted from HIV Network for Prevention Trials (HIVNET) behavioral criteria for high risk of HIV): (1) sexually active male who has sex with men (MSM), defined as (i) male who has had anal sex with male sexual partner or partners in the past year or (ii) a male who exchanged sex with male partner(s) for money or drugs in the past year; and (2) female and in a current relationship with a high risk male (active MSM, HIV positive male).
  • Any other significant disease, disorder or finding, which, in the opinion of the Investigator, may put the subject at risk because of participation in the study, may influence the result of the study, or may influence the subject's ability to participate in the study.
  • History of or current diagnosis of Diabetes mellitus.
  • History of or current diagnosis of autoimmune disease.
  • History of or current cardiac disease including history of myocardial infarction or arrhythmia.
  • Current diagnosis of active liver disease.
  • History of seizure disorder or currently taking anti-convulsant therapy that would interfere with safety evaluation.
  • Uncontrolled hypertension (defined as systolic blood pressure being greater than 140mm Hg or diastolic blood pressure being greater than 90mm Hg).
  • History of splenectomy.
  • Long term immunosuppressive use (defined as taken for 14 days or more in total at any time during the past 180 days) of high dose oral or parenteral glucocorticoids (high dose defined as prednisone >/=20 mg total daily dose, or equivalent dose of other glucocorticoids); or high-dose inhaled steroids (high dose defined as >800 mcg/day of beclomethasone dipropionate or equivalent); or any use of hepatotoxic or non-FDA approved medication.
  • Have an acute illness, including an oral temperature greater than or equal to 100.4 degrees Fahrenheit, within 7 days prior to the first vaccination.
  • Immunization against another pathogen within 14 days of planned injection.

Second vaccination exclusion criteria:

The following events associated with vaccine immunization constitute absolute contraindications to further administration of vaccine. The subject will not receive additional vaccination, but will continue with scheduled follow-up procedures except vaccination.

  1. Anaphylactic reaction following administration of vaccine.
  2. Pregnancy. If a woman reports having a positive home urine pregnancy test or a positive in clinic urine pregnancy test prior to a scheduled second vaccination, she is not eligible to receive the study vaccine. If she later returns to clinic and reports having a negative home urine pregnancy test and this is confirmed by a negative in clinic urine pregnancy test and a negative blood pregnancy test she may be eligible for the second vaccination if she is still within the vaccination window and no other exclusion criteria are met.

    The following adverse events constitute contraindications to administration of vaccine at that point in time. If any one of these adverse events occurs at the time scheduled for vaccination, the subject may be vaccinated at a later date (within 28 days of scheduled administration) or withdrawn at the discretion of the investigator. The subject will not receive additional vaccination, but will continue with all scheduled follow-up procedures except vaccination.

  3. Acute disease at the time of vaccination (acute disease is defined as the presence of a moderate or severe illness with or without fever). The vaccine dose can be administered to persons with a minor illness such as diarrhea, mild upper respiratory infection with or without low-grade febrile illness, i.e., temperature of <38°C (100.4°F).
  4. Temperature of >38°C (100.4°F) at the time of vaccination.
  5. Immunization against another pathogen within 14 days of vaccination
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01436357

Contacts
Contact: Paula J Lum (415) 476-4082 ext 411 plum@php.ucsf.edu

Locations
United States, California
University of California San Francisco - Tenderloin Clinical Research Center Recruiting
San Francisco, California, United States, 94102-4012
United States, Maryland
Johns Hopkins School of Public Health - Wood Clinic Recruiting
Baltimore, Maryland, United States, 21205-2400
Sponsors and Collaborators
  More Information

No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01436357     History of Changes
Other Study ID Numbers: 10-0069, N01AI40074
Study First Received: September 15, 2011
Last Updated: September 25, 2014
Health Authority: United States: Institutional Review Board
United States: Federal Government
United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Hepatitis C, vaccine, AdCh3NSmut1, MVA-NSmut

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections

ClinicalTrials.gov processed this record on October 02, 2014