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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00574600
• Other study ID #: HVTN 073/SAAVI 102
• Secondary ID: 10520SAAVI 102HV
• Status: Completed
• Phase: Phase 1
• Start date: November 2008
• Est. completion date: January 2013

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: January 2013
• Est. primary completion date: October 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• HIV Infections

Intervention

Biological:
• SAAVI DNA-C2 vaccine
DNA vaccine
• SAAVI MVA-C vaccine
Boost vaccine
• Placebo
Placebo vaccine

Locations

Country	Name	City	State
South Africa	Emavundleni CRS	Cape Town	Western Cape Province
South Africa	Soweto HVTN CRS	Johannesburg	Gauteng
United States	Brigham and Women's Hospital Vaccine CRS (BWH VCRS)	Boston	Massachusetts
United States	Fenway Health (FH) CRS	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	HIV Vaccine Trials Network

Countries where clinical trial is conducted

United States,  South Africa, 

References & Publications (3)

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. doi: 10.1099/vir.0.82493-0. Review. Erratum in: J Gen Virol. 2008 Feb;89(Pt 2):609. Goonetilleke, Nilu [added]. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Signs and symptoms of local and systemic reactogenicity, laboratory measures of safety, and adverse events		Measured throughout study
Secondary	T-cell responses as detected by HIV-1 specific interferon-gamma/interleukin-2 intracellular cytokine staining		Measured 2 weeks following the fourth and fifth vaccinations
Secondary	HIV-1-specific neutralizing and binding antibody assays		Measured 2 weeks following the fourth and fifth vaccinations

External Links

•   Click here for more information about preventive HIV vaccines
•   Haga clic aquí para ver información sobre este ensayo clínico en español