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

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Collaborator:	HIV Vaccine Trials Network
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00574600

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 I

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:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: HIV/AIDS

U.S. FDA Resources

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 ]

Estimated Enrollment:

48

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00574600

Locations

United States, Massachusetts
Fenway Community Health Clinical Research Site
Boston, Massachusetts, United States, 02115
Brigham and Women's Hospital CRS
Boston, Massachusetts, United States, 02115
United States, New York
Univ. of Rochester HVTN CRS
Rochester, New York, United States, 14642-0001

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

HIV Vaccine Trials Network

Investigators

Study Chair:	Glenda Gray	University of the Witswatersrand
Study Chair:	Kenneth Mayer	Fenway Community Health

More Information

Additional Information:

Click here for more information about preventive HIV vaccines This link exits the ClinicalTrials.gov site

Haga clic aquí para ver información sobre este ensayo clínico en español This link exits the ClinicalTrials.gov site

Publications:

Hanke T, McMichael AJ, Dorrell L. Clinical experience with plasmid DNA- and modified vaccinia virus Ankara-vectored human immunodeficiency virus type 1 clade A vaccine focusing on T-cell induction. J Gen Virol. 2007 Jan;88(Pt 1):1-12. Review.

Verrier F, Burda S, Belshe R, Duliege AM, Excler JL, Klein M, Zolla-Pazner S. A human immunodeficiency virus prime-boost immunization regimen in humans induces antibodies that show interclade cross-reactivity and neutralize several X4-, R5-, and dualtropic clade B and C primary isolates. J Virol. 2000 Nov;74(21):10025-33.

Williamson C, Morris L, Maughan MF, Ping LH, Dryga SA, Thomas R, Reap EA, Cilliers T, van Harmelen J, Pascual A, Ramjee G, Gray G, Johnston R, Karim SA, Swanstrom R. Characterization and selection of HIV-1 subtype C isolates for use in vaccine development. AIDS Res Hum Retroviruses. 2003 Feb;19(2):133-44.

Responsible Party:	Rona Siskind, DAIDS
ClinicalTrials.gov Identifier:	NCT00574600 History of Changes
Other Study ID Numbers:	HVTN 073, SAAVI 102, 10520
Study First Received:	December 13, 2007
Last Updated:	March 10, 2011
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 February 09, 2012