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Safety and Immune Response to Preventive HIV Immunization With Adenovirus Serotype 5 or 35 Vector

Phase 1
Completed
Conditions
HIV Infections
Interventions
Biological: rAd35
Biological: DNA Vaccine
Biological: rAd35 placebo
Biological: DNA Vaccine placebo
Biological: rAd5
Biological: rAd5 placebo
Registration Number
NCT00801697
Lead Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Brief Summary

This study will evaluate the safety and preliminary immune response to recombinant adenoviral serotype 35 and 5 HIV-1 vaccines in HIV-uninfected adults.

Detailed Description

One of the more promising approaches in the development of a preventive HIV vaccine uses a DNA plasmid to prime the immune response to an adenoviral vector boost. This primary purpose of this study is to evaluate the safety, tolerability, and immune response to recombinant adenoviral serotype 35 (rAd35) and serotype 5 (rAD5) HIV-1 vaccines in Ad-5 naive and Ad-5 exposed HIV-uninfected adults.

This study will last approximately 12 months. Participants will include those who are both rAD5-naive and rAD5-exposed and will be stratified into one of four groups. Each group will consist of two arms, one interventional and one control. Participants in Groups 1, 2, and 3 will be rAD5-naive. Participants in Group 4 will be rAD5-exposed.

Participants in Group 1 will receive an injection of rAD35 vaccine or placebo at study entry and an injection of rAD5 vaccine or placebo at Month 6 with nine follow-up visits through Month 12. Participants in Groups 2, 3, and 4 will injections of DNA vaccinations or placebo at study entry and at Months 1 and 2, and an injection of rAD35 vaccine, rAD5 vaccine, or placebo at Month 6 with twelve follow-up visits though Month 12. A physical, questionnaire, and counseling will occur at all visits. Blood and urine collection will occur at most visits. A rectal swab will occur at selected visits. For females, a pregnancy test will occur at all visits.

Participants will be contacted for safety follow-ups after the injection every year for 5 years. Health and adverse events will be recorded. Participants will not need to return to the study clinic unless HIV confirmatory testing is needed.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
192
Inclusion Criteria
  • Good general health
  • Access to a participating HVTN clinical research site and willingness to be followed for the duration of the study
  • Assessment of understanding, including understanding of Step Study results
  • Willing to receive HIV test results
  • Willing to discuss HIV infection risks, agree to HIV risk reduction counseling, and willing to continue 5 years of annual follow-up contact
  • Willing to commit to maintaining behavior consistent with low risk of HIV exposure through the last required protocol visit
  • Considered low risk for HIV infection after clinical staff assessment. More information on this criterion can be found in the protocol.
  • Certain laboratory values. More information on this criterion can be found in the protocol.
  • Negative Hepatitis B surface antigen
  • Negative anti-Hepatitis C virus antibodies
  • For females, agree to use effective contraception from at least 21 days prior to enrollment through the last protocol visit. More information on this criterion can be found in the protocol.
Exclusion Criteria
  • HIV-infected
  • Active drug or alcohol abuse within 12 months prior to study entry
  • History of newly acquired sexually transmitted infections. More information on this criterion can be found in the protocol.
  • Experimental vaccines received within 5 years prior to study entry
  • Immunosuppressive medications received within 168 days prior to first vaccination
  • Blood products received within 120 days prior to first vaccination
  • Immunoglobulin received within 60 days prior to first vaccination
  • Live attenuated vaccines received within 30 days prior to first vaccination
  • Investigational research agents received within 30 days prior to first vaccination
  • Intent to participate in another study of an investigational research agent during planned duration of the study
  • Any vaccines that not live attenuated vaccines and were received within 14 days prior to first vaccination
  • Allergy treatment with antigen injections within 30 days prior to first vaccination or scheduled within 14 days after first vaccination
  • Clinically significant medical condition, findings, results, or history with implications for current health. More information on this criterion can be found in the protocol.
  • Serious adverse reactions to vaccines
  • Autoimmune disease
  • Immunodeficiency
  • Active Syphilis infection within the past 6 months
  • Asthma. More information on this criterion can be found in the protocol.
  • Diabetes mellitus
  • Thyroidectomy or thyroid disease requiring medication during the last 12 months
  • Hypertension. More information on this criterion can be found in the protocol.
  • Body mass index greater than 35 or 40. More information on this criterion can be found in the protocol.
  • Bleeding disorder
  • Malignancy
  • Seizure disorder
  • Asplenia
  • Psychiatric condition that precludes compliance with the protocol
  • Any other clinically significant condition or laboratory abnormality that, in the opinion of the investigator, would interfere with the study
  • Pregnant or breastfeeding

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
1ArAd35rAD5-naive participants will receive rAd35 intramuscularly at study entry and rAd5 intramuscularly at Month 6
2ADNA VaccinerAD5-naive participants will receive DNA vaccine intramuscularly at study entry and Months 1 and 2 and rAd5 intramuscularly at Month 6
1ArAd5rAD5-naive participants will receive rAd35 intramuscularly at study entry and rAd5 intramuscularly at Month 6
1BrAd35 placeboParticipants will receive rAd35 placebo intramuscularly at study entry and rAd5 placebo intramuscularly at Month 6
1BrAd5 placeboParticipants will receive rAd35 placebo intramuscularly at study entry and rAd5 placebo intramuscularly at Month 6
2BDNA Vaccine placeboParticipants will receive DNA vaccine placebo intramuscularly at study entry and Months 1 and 2 and rAd5 placebo intramuscularly at Month 6
2BrAd5 placeboParticipants will receive DNA vaccine placebo intramuscularly at study entry and Months 1 and 2 and rAd5 placebo intramuscularly at Month 6
2ArAd5rAD5-naive participants will receive DNA vaccine intramuscularly at study entry and Months 1 and 2 and rAd5 intramuscularly at Month 6
3BrAd35 placeboParticipants will receive DNA vaccine placebo intramuscularly at study entry and Months 1 and 2 and rAd35 placebo intramuscularly at Month 6
4ArAd35Participants will receive DNA vaccine intramuscularly at study entry and Months 1 and 2 and rAd35 intramuscularly at Month 6
4BrAd35 placeboParticipants will receive DNA vaccine placebo intramuscularly at study entry and Months 1 and 2 and rAd35 placebo intramuscularly at Month 6
3ArAd35Participants will receive DNA vaccine intramuscularly at study entry and Months 1 and 2 and rAd35 intramuscularly at Month 6
3BDNA Vaccine placeboParticipants will receive DNA vaccine placebo intramuscularly at study entry and Months 1 and 2 and rAd35 placebo intramuscularly at Month 6
3ADNA VaccineParticipants will receive DNA vaccine intramuscularly at study entry and Months 1 and 2 and rAd35 intramuscularly at Month 6
4ADNA VaccineParticipants will receive DNA vaccine intramuscularly at study entry and Months 1 and 2 and rAd35 intramuscularly at Month 6
4BDNA Vaccine placeboParticipants will receive DNA vaccine placebo intramuscularly at study entry and Months 1 and 2 and rAd35 placebo intramuscularly at Month 6
Primary Outcome Measures
NameTimeMethod
Local and systemic reactogenicity signs and symptoms, laboratory measures of safety, and adverse and expedited adverse eventsThroughout study
Magnitude and frequency of immune responses between HIV-1 clade A env rAD35 and rAd5 vaccines when given as a boost after DNA vaccineAt Week 4 following the fourth vaccination
Magnitude and frequency of immune responses between clade A env rAD35 vaccine primed by Ad35 versus DNAAt Week 4 following the last vaccination
Magnitude and frequency of immune responses of HIV-1 clade A env rAD35 vaccine when given as a boostAt Week 4 following the fourth vaccination
Secondary Outcome Measures
NameTimeMethod
Immunogenicity of HIV-1 clade A env rAD35 vaccine given as a primeAt Week 4 following the first vaccination

Trial Locations

Locations (10)

Columbia P&S CRS

🇺🇸

New York, New York, United States

New York Blood Center CRS

🇺🇸

New York, New York, United States

University of Rochester Vaccines to Prevent HIV Infection CRS

🇺🇸

Rochester, New York, United States

Vanderbilt Vaccine (VV) CRS

🇺🇸

Nashville, Tennessee, United States

Alabama CRS

🇺🇸

Birmingham, Alabama, United States

Bridge HIV CRS

🇺🇸

San Francisco, California, United States

The Hope Clinic of the Emory Vaccine Center CRS

🇺🇸

Decatur, Georgia, United States

Brigham and Women's Hospital Vaccine CRS (BWH VCRS)

🇺🇸

Boston, Massachusetts, United States

Fenway Health (FH) CRS

🇺🇸

Boston, Massachusetts, United States

Seattle Vaccine and Prevention CRS

🇺🇸

Seattle, Washington, United States

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