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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
HIV Vaccine Trials Network
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00801697
First received: December 2, 2008
Last updated: May 27, 2014
Last verified: May 2014
  Purpose

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


Condition Intervention Phase
HIV Infections
Biological: DNA Vaccine
Biological: DNA Vaccine placebo
Biological: rAd35
Biological: rAd35 placebo
Biological: rAd5
Biological: rAd5 placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Prevention
Official Title: A Phase 1B Clinical Trial to Evaluate the Safety and Immunogenicity of Recombinant Adenoviral Subtype 35 (rAd35) and Subtype 5 (rAd5) HIV-1 Vaccines When Given as a Heterologous Prime-boost Regimen or as Boosts to a Recombinant DNA Vaccine in Healthy, Ad5-Naïve and Ad5-Exposed, Low Risk, HIV-1 Uninfected Adult Participants

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Local and systemic reactogenicity signs and symptoms, laboratory measures of safety, and adverse and expedited adverse events [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Magnitude and frequency of immune responses between HIV-1 clade A env rAD35 and rAd5 vaccines when given as a boost after DNA vaccine [ Time Frame: At Week 4 following the fourth vaccination ] [ Designated as safety issue: No ]
  • Magnitude and frequency of immune responses between clade A env rAD35 vaccine primed by Ad35 versus DNA [ Time Frame: At Week 4 following the last vaccination ] [ Designated as safety issue: No ]
  • Magnitude and frequency of immune responses of HIV-1 clade A env rAD35 vaccine when given as a boost [ Time Frame: At Week 4 following the fourth vaccination ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Immunogenicity of HIV-1 clade A env rAD35 vaccine given as a prime [ Time Frame: At Week 4 following the first vaccination ] [ Designated as safety issue: No ]

Enrollment: 192
Study Start Date: February 2009
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1A
rAD5-naive participants will receive rAd35 intramuscularly at study entry and rAd5 intramuscularly at Month 6
Biological: rAd35
VRC-HIVADV027-00-VP 1 x 10^10 PU administered as 1 mL
Biological: rAd5
4 mg VRC-HIVADV038-00-VP administered as 1 mL
Placebo Comparator: 1B
Participants will receive rAd35 placebo intramuscularly at study entry and rAd5 placebo intramuscularly at Month 6
Biological: rAd35 placebo
1 mL VRC-PBSPLA043-00-0VP
Biological: rAd5 placebo
1 mL VRC-DILUENT013-DIL-VP
Experimental: 2A
rAD5-naive participants will receive DNA vaccine intramuscularly at study entry and Months 1 and 2 and rAd5 intramuscularly at Month 6
Biological: DNA Vaccine
4 mg VRC-HIVDNA044-00-VP administered as 1 mL
Biological: rAd5
4 mg VRC-HIVADV038-00-VP administered as 1 mL
Placebo Comparator: 2B
Participants will receive DNA vaccine placebo intramuscularly at study entry and Months 1 and 2 and rAd5 placebo intramuscularly at Month 6
Biological: DNA Vaccine placebo
1 mL VRC-PBSPLA043-00-VP
Biological: rAd5 placebo
1 mL VRC-DILUENT013-DIL-VP
Experimental: 3A
Participants will receive DNA vaccine intramuscularly at study entry and Months 1 and 2 and rAd35 intramuscularly at Month 6
Biological: DNA Vaccine
4 mg VRC-HIVDNA044-00-VP administered as 1 mL
Biological: rAd35
VRC-HIVADV027-00-VP 1 x 10^10 PU administered as 1 mL
Placebo Comparator: 3B
Participants will receive DNA vaccine placebo intramuscularly at study entry and Months 1 and 2 and rAd35 placebo intramuscularly at Month 6
Biological: DNA Vaccine placebo
1 mL VRC-PBSPLA043-00-VP
Biological: rAd35 placebo
1 mL VRC-PBSPLA043-00-0VP
Experimental: 4A
Participants will receive DNA vaccine intramuscularly at study entry and Months 1 and 2 and rAd35 intramuscularly at Month 6
Biological: DNA Vaccine
4 mg VRC-HIVDNA044-00-VP administered as 1 mL
Biological: rAd35
VRC-HIVADV027-00-VP 1 x 10^10 PU administered as 1 mL
Placebo Comparator: 4B
Participants will receive DNA vaccine placebo intramuscularly at study entry and Months 1 and 2 and rAd35 placebo intramuscularly at Month 6
Biological: DNA Vaccine placebo
1 mL VRC-PBSPLA043-00-VP
Biological: rAd35 placebo
1 mL VRC-PBSPLA043-00-0VP

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.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  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: NCT00801697

Locations
United States, Alabama
Alabama CRS
Birmingham, Alabama, United States, 35294
United States, California
Bridge HIV CRS
San Francisco, California, United States, 94143
United States, Georgia
The Hope Clinic of the Emory Vaccine Center CRS
Decatur, Georgia, United States, 30030
United States, Massachusetts
Brigham and Women's Hospital Vaccine CRS (BWH VCRS)
Boston, Massachusetts, United States, 02115-6110
Fenway Health (FH) CRS
Boston, Massachusetts, United States, 02215-4302
United States, New York
New York Blood Center CRS
New York, New York, United States, 10065
Columbia P&S CRS
New York, New York, United States, 10032-3732
University of Rochester Vaccines to Prevent HIV Infection CRS
Rochester, New York, United States, 14642
United States, Tennessee
Vanderbilt Vaccine (VV) CRS
Nashville, Tennessee, United States, 37232-2582
United States, Washington
Seattle Vaccine and Prevention CRS
Seattle, Washington, United States, 98109-1024
Sponsors and Collaborators
HIV Vaccine Trials Network
Investigators
Study Chair: Jonathan Fuchs, MD, MPH SFDPH/UCSF
Study Chair: Pierre-Alexandre Bart, MD CHUV (Lausanne)
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00801697     History of Changes
Other Study ID Numbers: HVTN 077, 10702
Study First Received: December 2, 2008
Last Updated: May 27, 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
Adenovirus

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 August 28, 2014