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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00801697
• Other study ID #: HVTN 077
• Secondary ID: 10702
• Status: Completed
• Phase: Phase 1
• Start date: February 2009
• Est. completion date: April 2015

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

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

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 information / eligibility

• Status: Completed
• Enrollment: 192
• Est. completion date: April 2015
• Est. primary completion date: February 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• HIV Infections

Intervention

Biological:
• DNA Vaccine
4 mg VRC-HIVDNA044-00-VP administered as 1 mL
• DNA Vaccine placebo
1 mL VRC-PBSPLA043-00-VP
• rAd35
VRC-HIVADV027-00-VP 1 x 10^10 PU administered as 1 mL
• rAd35 placebo
1 mL VRC-PBSPLA043-00-0VP
• rAd5
4 mg VRC-HIVADV038-00-VP administered as 1 mL
• rAd5 placebo
1 mL VRC-DILUENT013-DIL-VP

Locations

Country	Name	City	State
United States	Alabama CRS	Birmingham	Alabama
United States	Brigham and Women's Hospital Vaccine CRS (BWH VCRS)	Boston	Massachusetts
United States	Fenway Health (FH) CRS	Boston	Massachusetts
United States	The Hope Clinic of the Emory Vaccine Center CRS	Decatur	Georgia
United States	Vanderbilt Vaccine (VV) CRS	Nashville	Tennessee
United States	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	Bridge HIV CRS	San Francisco	California
United States	Seattle Vaccine and Prevention CRS	Seattle	Washington

Sponsors (2)

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

Country where clinical trial is conducted

United States, 

References & Publications (3)

Buchbinder SP, Mehrotra DV, Duerr A, Fitzgerald DW, Mogg R, Li D, Gilbert PB, Lama JR, Marmor M, Del Rio C, McElrath MJ, Casimiro DR, Gottesdiener KM, Chodakewitz JA, Corey L, Robertson MN; Step Study Protocol Team. Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet. 2008 Nov 29;372(9653):1881-1893. doi: 10.1016/S0140-6736(08)61591-3. Epub 2008 Nov 13. — View Citation

Priddy FH, Brown D, Kublin J, Monahan K, Wright DP, Lalezari J, Santiago S, Marmor M, Lally M, Novak RM, Brown SJ, Kulkarni P, Dubey SA, Kierstead LS, Casimiro DR, Mogg R, DiNubile MJ, Shiver JW, Leavitt RY, Robertson MN, Mehrotra DV, Quirk E; Merck V520-016 Study Group. Safety and immunogenicity of a replication-incompetent adenovirus type 5 HIV-1 clade B gag/pol/nef vaccine in healthy adults. Clin Infect Dis. 2008 Jun 1;46(11):1769-81. doi: 10.1086/587993. — View Citation

Sheets RL, Stein J, Bailer RT, Koup RA, Andrews C, Nason M, He B, Koo E, Trotter H, Duffy C, Manetz TS, Gomez P. Biodistribution and toxicological safety of adenovirus type 5 and type 35 vectored vaccines against human immunodeficiency virus-1 (HIV-1), Ebola, or Marburg are similar despite differing adenovirus serotype vector, manufacturer's construct, or gene inserts. J Immunotoxicol. 2008 Jul;5(3):315-35. doi: 10.1080/15376510802312464. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Local and systemic reactogenicity signs and symptoms, laboratory measures of safety, and adverse and expedited adverse events		Throughout study
Primary	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
Primary	Magnitude and frequency of immune responses between clade A env rAD35 vaccine primed by Ad35 versus DNA		At Week 4 following the last vaccination
Primary	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	Immunogenicity of HIV-1 clade A env rAD35 vaccine given as a prime		At Week 4 following the first vaccination

External Links

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