Safety of and Immune Response to an Adenoviral HIV-1 Vaccine in Healthy Adults - Full Text View

Sponsored by:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00618605

Purpose

Successful control of the HIV epidemic will require a safe and effective vaccine to be developed. A successful vaccine will need to stimulate a widespread immune response. The purpose of this study is to determine the safety of and immune response to an adenovirus serotype HIV vaccine in HIV uninfected adults.

Condition	Intervention	Phase
HIV Infections	Biological: Ad26.ENVA.01 HIV-1 vaccine	Phase I

MedlinePlus related topics: AIDS

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Caregiver), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	A Phase 1 Randomized, Double-Blind, Placebo Controlled Dose Escalation Clinical Trial to Evaluate the Safety and Immunogenicity of Recombinant Adenovirus Serotype 26 HIV-1 Vaccine (Ad26.ENVA.01) in Healthy, HIV-1 Uninfected Adults

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

Primary Outcome Measures:

Local and systemic reactions to injection [ Time Frame: After each injection ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Humoral immune responses, such as neutralizing and binding antibodies to HIV and Ad26 [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Cell mediated immunity, including T-cell gamma interferon responses and assessment of T-cell responses by flow cytometry [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Genotyping [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Stored samples may be used to perform additional assays for further evaluation of immunogenicity and to support standardization and validation of new assays such as epitope mapping, flow cytometry, and/or tetramer analysis. [ Time Frame: After study follow-up ] [ Designated as safety issue: No ]

Estimated Enrollment:	48
Study Start Date:	June 2008
Estimated Study Completion Date:	October 2010
Estimated Primary Completion Date:	October 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental 3 injections of Ad26.ENVA.01 HIV-1 vaccine or placebo at 1 x 10^9 virus particles (VP) given at Days 0, 28, and 168	Biological: Ad26.ENVA.01 HIV-1 vaccine Recombinant adenovirus serotype 26 HIV-1 vaccine
2: Experimental 3 injections of Ad26.ENVA.01 HIV-1 vaccine or placebo at 1 x 10^10 VP given at Days 0, 28, and 168	Biological: Ad26.ENVA.01 HIV-1 vaccine Recombinant adenovirus serotype 26 HIV-1 vaccine
3: Experimental 3 injections of Ad26.ENVA.01 HIV-1 vaccine or placebo at 1 x 10^11 VP given at Days 0, 28, and 168	Biological: Ad26.ENVA.01 HIV-1 vaccine Recombinant adenovirus serotype 26 HIV-1 vaccine
4: Experimental 2 injections of Ad26.ENVA.01 HIV-1 vaccine or placebo at a dose to be determined by the safety data from Arms 1, 2 and 3 given at Days 0 and 168	Biological: Ad26.ENVA.01 HIV-1 vaccine Recombinant adenovirus serotype 26 HIV-1 vaccine

Detailed Description:

HIV infection continues to spread at pandemic levels throughout the world. Control of this pandemic can only be achieved with the development of a safe and effective preventive HIV vaccine. A vaccine that will prevent HIV infection will elicit a strong immune response from both CD4 and CD8 cells.

Recombinant adenovirus serotype vectors have been shown to elicit just such a response. The purpose of this study is to determine the safety and immunogenicity of the recombinant adenovirus serotype 26 preventive HIV-1 vaccine.

This study will last 12 months. Participants will be randomly assigned to one of four arms that will receive different doses of the vaccine or placebo administered via intermuscular injection. Participants in Arms 1, 2, and 3 will all receive 3 injections. Each injection will contain the same dose of vaccine. Arm 4 will receive 2 injections of a dose of vaccine that will be determined by the safety data from Arms 1, 2, and 3. Participants will be enrolled sequentially, from lowest to highest dose of vaccine, into Arms 1, 2, and 3. Arms will begin enrollment only following review of safety data from the previous group. After the Day 42 safety data from Arms 1, 2, and 3 have been reviewed, the dose for Arm 4 will be determined, and enrollment into that arm will begin.

There will be 10 study visits in this study. Participants in Arms 1, 2, and 3 will receive injections on Days 0, 28, and 168. Participants in Arm 4 will receive injections on Days 0 and 168. Participants will be asked to record their temperature and other side effects in a symptom log for 7 days after each injection. Risk reduction/pregnancy prevention counseling will occur at visits 1 through 9, and physical exams will occur at all visits. At most visits, blood, urine, and oral swab collection will occur. At some visits, HIV testing and pregnancy testing will occur.

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 with normal hematological, hepatic and renal functions
Demonstrated understanding of study
Willing to receive HIV test results
HIV-1 and -2 uninfected
Hepatitis B surface antigen negative
Anti-hepatitis C virus (anti-HCV) negative antibody or negative HCV PCR if anti-HCV is positive
Appropriate hemoglobin, white blood cell, lymphocyte, and platelet count values as defined in the study protocol
Certain laboratory values as defined in the study protocol
Adequate contraception from at least 21 days prior to study entry through visit 10

Exclusion Criteria:

HIV vaccines or placebos in prior HIV vaccine trial
Immunosuppressive medications within 168 days prior to first injection. Participants taking corticosteroid nasal spray or topical corticosteroids are not excluded.
Blood products within 120 days prior to first injection
Immunoglobulin within 60 days prior to first injection
Investigational agents within 30 days prior to first injections
Live attenuated vaccine within 30 days prior to first injection
Any vaccine not a live attenuated vaccine within 14 days prior to first injection
Any clinically significant medical condition that, in the opinion of the investigator, may interfere with the study
Any medical, psychiatric, occupational, or social condition or responsibility that, in the opinion of the investigator, would interfere with the study
Serious adverse reaction to vaccines. Participants who had a nonanaphylactic adverse reaction to pertussis vaccine as a child are not excluded.
Known autoimmune disease
Known immunodeficiency
Asthma other than mild and/or well-controlled asthma
Active syphilis infection. Those fully treated for syphilis over 6 months prior to study entry are not excluded.
Diabetes mellitus type 1 or 2
Thyroidectomy or thyroid disease requiring medication within 12 months prior to study entry
Angioedema in the 3 years prior to study entry if the episodes are considered serious or have required medication within the last 2 years
Hypertension. More information on this criterion can be found in the protocol.
Body mass index (BMI) of 40 or higher OR BMI of 35 or greater, if other cardiovascular risk factors. More information on this criterion can be found in the protocol.
Bleeding disorder
Malignancy, unless it has been surgically removed and, in the opinion of the investigator, is not likely to recur during the study period
Seizure disorder or occurrence of seizure in the 3 years prior to study entry. Participants who have not required medications or had a seizure for prior 3 years are not excluded.
Absence of a functional spleen
Psychiatric condition within the last 3 years. More information on this criterion can be found in the study protocol.
Individuals at high-risk of acquiring HIV infection
Presence of pre-existing neutralizing antibodies for Adenovirus 26
Pregnancy or breastfeeding

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00618605

Locations

United States, Massachusetts
Brigham and Womens Hospital	Recruiting
Boston, Massachusetts, United States, 02115
Contact: Lindsey R. Baden, MD 617-732-6801 lbaden@partners.org
Principal Investigator: Lindsey R. Baden, MD

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Chair:	Lindsey Baden, MD	Brigham and Women's Hospital
Study Chair:	Dan Barouch, MD, PhD	Beth Israel Deaconess Medical Center
Study Chair:	Raphael Dolin, MD	Brigham and Women's Hospital

More Information

Additional Information:

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

Publications:

Abbink P, Lemckert AA, Ewald BA, Lynch DM, Denholtz M, Smits S, Holterman L, Damen I, Vogels R, Thorner AR, O'Brien KL, Carville A, Mansfield KG, Goudsmit J, Havenga MJ, Barouch DH. Comparative seroprevalence and immunogenicity of six rare serotype recombinant adenovirus vaccine vectors from subgroups B and D. J Virol. 2007 May;81(9):4654-63. Epub 2007 Feb 28.

Liniger M, Zuniga A, Naim HY. Use of viral vectors for the development of vaccines. Expert Rev Vaccines. 2007 Apr;6(2):255-66. Review.

Roberts DM, Nanda A, Havenga MJ, Abbink P, Lynch DM, Ewald BA, Liu J, Thorner AR, Swanson PE, Gorgone DA, Lifton MA, Lemckert AA, Holterman L, Chen B, Dilraj A, Carville A, Mansfield KG, Goudsmit J, Barouch DH. Hexon-chimaeric adenovirus serotype 5 vectors circumvent pre-existing anti-vector immunity. Nature. 2006 May 11;441(7090):239-43. Epub 2006 Apr 16.

Responsible Party:	Regulatory Affairs Branch, DAIDS, NIAID ( Mary Ann Luzar, PhD Chief Regulatory Affairs Branch )
Study ID Numbers:	Ad26.ENVA.01
Study First Received:	February 18, 2008
Last Updated:	December 2, 2008
ClinicalTrials.gov Identifier:	NCT00618605 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 Preventative Vaccine

Study placed in the following topic categories:

Virus Diseases
Sexually Transmitted Diseases, Viral
HIV Infections
Adenoviridae Infections
Sexually Transmitted Diseases

Acquired Immunodeficiency Syndrome
Healthy
Retroviridae Infections
Immunologic Deficiency Syndromes

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 May 07, 2009