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

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00801697

Collaborator

HIV Vaccine Trials Network (Other)

192

Enrollment

Locations

Arms

73.9

Duration (Months)

19.2

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Biological: DNA Vaccine Biological: DNA Vaccine placebo Biological: rAd35 Biological: rAd35 placebo Biological: rAd5 Biological: rAd5 placebo	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

192 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Care Provider)

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

Study Start Date :

Feb 1, 2009

Actual Primary Completion Date :

Feb 1, 2011

Actual Study Completion Date :

Apr 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

Local and systemic reactogenicity signs and symptoms, laboratory measures of safety, and adverse and expedited adverse events [Throughout study]
Magnitude and frequency of immune responses between HIV-1 clade A env rAD35 and rAd5 vaccines when given as a boost after DNA vaccine [At Week 4 following the fourth vaccination]
Magnitude and frequency of immune responses between clade A env rAD35 vaccine primed by Ad35 versus DNA [At Week 4 following the last vaccination]
Magnitude and frequency of immune responses of HIV-1 clade A env rAD35 vaccine when given as a boost [At Week 4 following the fourth vaccination]

Secondary Outcome Measures

Immunogenicity of HIV-1 clade A env rAD35 vaccine given as a prime [At Week 4 following the first vaccination]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Locations

	Site	City	State	Country	Postal Code
1	Alabama CRS	Birmingham	Alabama	United States	35294
2	Bridge HIV CRS	San Francisco	California	United States	94143
3	The Hope Clinic of the Emory Vaccine Center CRS	Decatur	Georgia	United States	30030
4	Brigham and Women's Hospital Vaccine CRS (BWH VCRS)	Boston	Massachusetts	United States	02115-6110
5	Fenway Health (FH) CRS	Boston	Massachusetts	United States	02215-4302
6	Columbia P&S CRS	New York	New York	United States	10032-3732
7	New York Blood Center CRS	New York	New York	United States	10065
8	University of Rochester Vaccines to Prevent HIV Infection CRS	Rochester	New York	United States	14642
9	Vanderbilt Vaccine (VV) CRS	Nashville	Tennessee	United States	37232-2582
10	Seattle Vaccine and Prevention CRS	Seattle	Washington	United States	98109-1024