Safety and Immune Response to Preventive HIV Immunization With Adenovirus Serotype 5 or 35 Vector - Full Text View

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Collaborator:	HIV Vaccine Trials Network
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00801697

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 I

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Caregiver), Parallel Assignment
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:

MedlinePlus related topics: AIDS

U.S. FDA Resources

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 ]

Estimated Enrollment:	192
Study Start Date:	January 2009
Estimated Study Completion Date:	July 2011
Estimated Primary Completion Date:	July 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1A: Experimental 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
1B: Placebo Comparator 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
2A: Experimental 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
2B: Placebo Comparator 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
3A: Experimental 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
3B: Placebo Comparator 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
4A: Experimental 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
4B: Placebo Comparator 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.

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00801697

Locations

United States, Alabama
Alabama Vaccine CRS	Recruiting
Birmingham, Alabama, United States, 35294-2050
Contact: Susan F. Duncan, CRNP, MSN 205-975-2840 sduncan@uab.edu
Principal Investigator: Paul A. Goepfert, MD
United States, California
San Francisco Vaccine and Prevention CRS	Not yet recruiting
San Francisco, California, United States
Contact: Theresa M. Wagner, MPH 415-554-4294 Theresa.Wagner@sfdph.org
Principal Investigator: Susan P. Buchbinder, MD
United States, Georgia
Hope Clinic of the Emory Vaccine Center CRS	Not yet recruiting
Decatur, Georgia, United States, 30030
Contact: Jane Skvarich, RN, MN 404-377-3719 ext 19 jskvari@emory.edu
Principal Investigator: Mark Mulligan, MD
United States, Massachusetts
Brigham and Women's Hospital	Recruiting
Boston, Massachusetts, United States, 02115
Contact: Lizanne C. Noble, MPH 617-732-5394 lnoble@partners.org
United States, New York
Univ. of Rochester HVTN CRS	Recruiting
Rochester, New York, United States, 14642-0001
Contact: Catherine A. Bunce, RN, MS, CCRC 585-275-5744 catherine_bunce@urmc.rochester.edu
Principal Investigator: Michael C. Keefer, MD
NY Blood Ctr./Bronx CRS	Not yet recruiting
Bronx, New York, United States, 10455
Contact: Debbie Lucy 718-402-0743 ext 309 dlucy@nybloodcenter.org
Principal Investigator: Beryl Koblin, PhD
NY Blood Ctr./Union Square CRS	Not yet recruiting
New York, New York, United States, 10003
Contact: Krista Goodman 212-388-0008 ext 20 kgoodman@nybloodcenter.org
Principal Investigator: Beryl Koblin, PhD
United States, Washington
FHCRC/UW Vaccine CRS	Recruiting
Seattle, Washington, United States, 98104
Contact: David Berger, RN 206-667-2344 dberger@fhcrc.org

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

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:

Click here for more information on preventive HIV vaccines This link exits the ClinicalTrials.gov site

Publications:

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; the 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. Epub 2008 Nov 13.

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.

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.

Responsible Party:	DAIDS ( Rona Siskind )
Study ID Numbers:	HVTN 077
Study First Received:	December 2, 2008
Last Updated:	September 1, 2009
ClinicalTrials.gov Identifier:	NCT00801697 History of Changes
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:

Virus Diseases
Sexually Transmitted Diseases, Viral
RNA Virus Infections
Slow Virus Diseases
Immune System Diseases
HIV Infections

Sexually Transmitted Diseases
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Infection
Retroviridae Infections
Immunologic Deficiency Syndromes

ClinicalTrials.gov processed this record on February 09, 2010