Safety of and Immune Response to Two HIV Vaccines: SAAVI DNA-C2 Boosted With SAAVIMVA-C, in HIV-Negative Adults

This study has been completed.
Sponsor:
Collaborator:
HIV Vaccine Trials Network
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00574600
First received: December 13, 2007
Last updated: June 23, 2014
Last verified: June 2014
  Purpose

The purpose of this study is to evaluate the safety of and immune response to an experimental DNA HIV vaccine followed by boosting with an experimental modified vaccinia HIV vaccine (MVA) in HIV uninfected adults.


Condition Intervention Phase
HIV Infections
Biological: SAAVI DNA-C2 vaccine
Biological: SAAVI MVA-C vaccine
Biological: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: A Phase 1 Placebo-controlled Clinical Trial to Evaluate the Safety and Immunogenicity of SAAVI DNA-C2 Vaccine Boosted by SAAVI MVA-C Vaccine, in HIV Uninfected Healthy Vaccinia Naive Adult Participants in South Africa and the United States

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Signs and symptoms of local and systemic reactogenicity, laboratory measures of safety, and adverse events [ Time Frame: Measured throughout study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • T-cell responses as detected by HIV-1 specific interferon-gamma/interleukin-2 intracellular cytokine staining [ Time Frame: Measured 2 weeks following the fourth and fifth vaccinations ] [ Designated as safety issue: No ]
  • HIV-1-specific neutralizing and binding antibody assays [ Time Frame: Measured 2 weeks following the fourth and fifth vaccinations ] [ Designated as safety issue: No ]

Enrollment: 48
Study Start Date: November 2008
Study Completion Date: January 2013
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vaccine
SAAVI DNA-C2 administered as 1 ml intramuscularly in either deltoid at study entry and Months 1 and 2; SAAVI MVA-C administered as 0.5 ml intramuscularly in either deltoid at Months 4 and 5
Biological: SAAVI DNA-C2 vaccine
DNA vaccine
Biological: SAAVI MVA-C vaccine
Boost vaccine
Placebo Comparator: Placebo
Placebo administered at Months 0, 1, 2, 4 and 5
Biological: Placebo
Placebo vaccine

Detailed Description:

The worldwide HIV/AIDS epidemic may only be controlled through development and utilization of a safe and effective vaccine that will prevent HIV infection. Due to the high prevalence of HIV-1 subtype C in southern Africa, the South African AIDS Vaccine Initiative (SAAVI), the HIV Vaccine Trials Network (HVTN) and the National Institute of Allergy and Infectious Diseases (NIAID) are evaluating two subtype C HIV vaccines, SAAVI DNA-C2 and SAAVI MVA-C through this study . These two vaccines will be used together in a prime-boost regimen. The SAAVI DNA-C2 vaccine is a multigene DNA vaccine consisting of two DNA plasmids in equal amounts that express an HIV-1 subtype C polyprotein comprising of Gag-Reverse Transcriptase-Tat-Nef and an HIV-1 subtype C truncated Env. SAAVI MVA-C is a recombinant MVA vaccine expressing the same immunogens as the SAAVI DNA-C2 vaccine. MVA is a highly attenuated vaccinia virus. The purpose of this study is to evaluate the safety and immunogenicity of an experimental DNA HIV vaccine, SAAVI DNA C2, followed by boosting with an experimental recombinant MVA HIV vaccine, SAAVI MVA-C, in HIV uninfected adults.

Participants will actively participate in this study for 12 months and will then be contacted and asked questions about their health once annually for 3 years following initial study injection. Participants will be randomly assigned to receive either the SAAVI prime-boost preventive vaccine regimen or placebo. Vaccination with the SAAVI DNA-C2 vaccine will occur at Months 0, 1, and 2; boost vaccinations with the SAAVI MVA-C vaccine will occur at Months 4 and 5. Additional study visits will occur at Weeks 2, 6, 10, 16, 18, and 20 and Days 147, 154, 273, and 364.

Study procedures include physical exams, blood and urine collection, HIV testing, an electrocardiogram, and questionnaire. Some blood collected from participants will be stored and used in future research. Risk-reduction counseling will be conducted at all study visits.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Laboratory test results within specified ranges [complete blood count, chemistries, cardiac troponin T, urinalysis]
  • Good general health
  • HIV-1 and -2 uninfected
  • Have access to a participating HIV Vaccine Trials Unit (HVTU) and willing to be followed for the duration of the study
  • Willing to receive HIV test results
  • Negative hepatitis B surface antigen
  • Negative hepatitis C virus (HCV) antibodies OR negative HCV PCR if anti-HCV test is positive
  • Willing to use acceptable forms of contraception from at least 21 days prior to enrollment through the duration of the study

Exclusion Criteria:

  • History of vaccination against smallpox
  • HIV vaccines in prior HIV vaccine trial
  • Immunosuppressive medications within 168 days prior to first study vaccination
  • Blood products within 120 days prior to first study vaccination
  • Immunoglobulin within 60 days prior to first study vaccination
  • Live attenuated vaccines within 30 days prior to first study vaccination or scheduled within 14 days after other vaccination (e.g., measles, mumps, and rubella [MMR]; oral polio vaccine [OPV]; varicella; yellow fever; influenza vaccine in nasal form)
  • Investigational research agents within 30 days prior to first study vaccination
  • Any vaccines that are not live attenuated vaccines within 14 days prior to first study vaccination
  • Allergy treatment with antigen injections within 30 days prior to first vaccination or scheduled within 14 days after vaccination
  • Received investigational research agents within 30 days prior to first vaccination
  • Current tuberculosis (TB) prophylaxis or therapy
  • Recreational cocaine or methamphetamine use within the last 12 months prior to first study vaccination
  • Clinically significant medical condition, abnormal physical exam findings, abnormal laboratory results, or past medical history that may affect current health. More information about this criterion can be found in the protocol.
  • Any medical, psychiatric, social, or job-related condition that would interfere with the study
  • Serious adverse reaction to vaccines. Participants who have had an adverse reaction to pertussis vaccine as a child are not excluded.
  • Hypersensitivity to eggs or egg products
  • Electrocardiogram (ECG) with clinically significant findings. More information about this criterion can be found in the protocol.
  • Risk factors for heart disease. More information about this criterion can be found in the protocol.
  • History of or current heart disease. More information about this criterion can be found in the protocol.
  • Autoimmune disease or immunodeficiency
  • Active syphilis infection. Participants with fully treated syphilis at least 6 months prior to study entry are not excluded.
  • Unstable asthma. More information about this criterion can be found in the protocol.
  • Diabetes mellitus type 1 or 2. Participants with a history of isolated gestational diabetes are not excluded.
  • History of thyroid removal or of thyroid disease requiring treatment in the 12 months prior to study entry
  • Serious angioedema within the past 3 years or requiring medication within 2 years of study entry
  • Hypertension that is not well-controlled
  • Body mass index (BMI) of 40 or more
  • Bleeding disorder
  • Cancer. Participants with surgically removed cancer that is unlikely to recur are not excluded.
  • Seizure disorder requiring medication within the last 3 years
  • Absence of spleen
  • Certain abnormal laboratory values
  • Psychiatric condition that would interfere with compliance with the protocol
  • Other conditions that, in the opinion of the investigator, would interfere with the study
  • Pregnancy or breastfeeding
  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: NCT00574600

Locations
United States, Massachusetts
Fenway Health (FH) CRS
Boston, Massachusetts, United States, 02215-4302
Brigham and Women's Hospital Vaccine CRS (BWH VCRS)
Boston, Massachusetts, United States, 02115-6110
South Africa
Soweto HVTN CRS
Johannesburg, Gauteng, South Africa, 1864
Emavundleni CRS
Cape Town, Western Cape Province, South Africa, 7750
Sponsors and Collaborators
HIV Vaccine Trials Network
Investigators
Study Chair: Glenda Gray University of the Witswatersrand
Study Chair: Kenneth Mayer Fenway Community Health
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00574600     History of Changes
Other Study ID Numbers: HVTN 073/SAAVI 102, 10520, SAAVI 102, HVTN 073
Study First Received: December 13, 2007
Last Updated: June 23, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
HIV Seronegativity
HIV Preventive Vaccine

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

ClinicalTrials.gov processed this record on July 28, 2014