Safety and Immune Response to a Recombinant Adenovirus HIV-1 Vaccine in Healthy Adults

Tracking Information
First Submitted Date ICMJE	June 10, 2008
First Posted Date ICMJE	June 12, 2008
Last Update Posted Date	May 9, 2018
Actual Study Start Date ICMJE	February 8, 2009
Actual Primary Completion Date	December 11, 2012 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: June 10, 2008)	Local and systemic adverse reactions [ Time Frame: Throughout study ]
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT00695877 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: June 10, 2008)	Humoral Immune response [ Time Frame: Throughout study ]; Cell mediated immunity [ Time Frame: Throughout study ]; Genotyping [ Time Frame: Throughout study ]
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Safety and Immune Response to a Recombinant Adenovirus HIV-1 Vaccine in Healthy Adults
Official Title ICMJE	A Phase I Randomized, Double-blind, Placebo Controlled Dose Escalation Clinical Trial to Evaluate the Safety and Immunogenicity of Recombinant Adenovirus Serotype 5 HVR48 HIV-1 Vaccine (Ad5HVR48.ENVA.01) in Healthy, HIV-1 Uninfected Adults (Ad5HVR48.ENVA.01 (rAd5HVR48) HIV-1/IPCAVD-002 Vaccine Study)
Brief Summary	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.
Detailed Description	Control of the HIV 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 5 preventive HIV-1 vaccine. This study will last 18 to 24 months. Participants will be randomly assigned to one of four arms that will receive vaccine or placebo administered via intramuscular injection. Participants in Arms 1, 2, and 3 will all receive 3 injections. Participants in Arm 4 will receive one injection. For most participants, there will be 10 study visits in this study; for participants in Arm 4, there will be only 7 visits. For Arms 1, 2, and 3, study visits will occur at baseline and on Days 0, 14, 28, 42, 56, 168, 182,196, and 365. Participants in Arms 1, 2, and 3 will receive injections on Days 0, 28, and 168. For participants in Arm 4, study visits will occur at baseline and on Days 0, 14, 28, 56, 168 and 365. Participants in Arm 4 will receive one injection only, on Day 0. Participants will be asked to record their temperature and other side effects in a symptom log for 3 days after each injection. Risk reduction/pregnancy prevention counseling and physical exams will occur at all visits. At most visits, blood, urine, and oral swab collection will occur. Samples collected will be stored for future testing. HIV testing and pregnancy testing will occur at select visits. At Years 2, 3, 4, and 5, participants will be followed-up by telephone, e-mail, or study visit to collect vital status, and information about any development of significant disability or incapacity, hospitalizations, or congenital anomalies. At these follow-up visits, blood collection will be optional.
Study Type ICMJE	Interventional
Study Phase	Phase 1
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Care Provider); Primary Purpose: Prevention
Condition ICMJE	HIV Infections
Intervention ICMJE	Biological: Ad5.ENVA.48 HIV-1 vaccine; Recombinant adenovirus serotype 5 HIV-1 vaccine
Study Arms	Experimental: 1 3 injections of rAd5.ENVA.48 HIV-1 vaccine or placebo at 1 x 10^9 virus particles (VP) given at Days 0, 28, and 168 Intervention: Biological: Ad5.ENVA.48 HIV-1 vaccine; Experimental: 2 3 injections of rAd5.ENVA.48 HIV-1 vaccine or placebo at 1 x 10^10 virus particles (VP) given at Days 0, 28, and 168 Intervention: Biological: Ad5.ENVA.48 HIV-1 vaccine; Experimental: 3 3 injections of rAd5.ENVA.48 HIV-1 vaccine or placebo at 1 x 10^11 virus particles (VP) given at Days 0, 28, and 168 Intervention: Biological: Ad5.ENVA.48 HIV-1 vaccine; Experimental: 4 1 injection of rAd5.ENVA.48 HIV-1 vaccine or placebo at a dose determined by the safety data from Arms 1, 2 and 3 given at Day 0. Intervention: Biological: Ad5.ENVA.48 HIV-1 vaccine
Publications *	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.; Stevens W, Kamali A, Karita E, Anzala O, Sanders EJ, Jaoko W, Kaleebu P, Mulenga J, Dally L, Fast P, Gilmour J, Farah B, Birungi J, Hughes P, Manigart O, Stevens G, Yates S, Thomson H, von Lieven A, Krebs M, Price MA, Stoll-Johnson L, Ketter N. Baseline morbidity in 2,990 adult African volunteers recruited to characterize laboratory reference intervals for future HIV vaccine clinical trials. PLoS One. 2008 Apr 30;3(4):e2043. doi: 10.1371/journal.pone.0002043.; Baden LR, Walsh SR, Seaman MS, Johnson JA, Tucker RP, Kleinjan JA, Gothing JA, Engelson BA, Carey BR, Oza A, Bajimaya S, Peter L, Bleckwehl C, Abbink P, Pau MG, Weijtens M, Kunchai M, Swann EM, Wolff M, Dolin R, Barouch DH. First-in-human evaluation of a hexon chimeric adenovirus vector expressing HIV-1 Env (IPCAVD 002). J Infect Dis. 2014 Oct 1;210(7):1052-61. doi: 10.1093/infdis/jiu217. Epub 2014 Apr 8.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: June 10, 2008)	48
Original Estimated Enrollment ICMJE	Same as current
Actual Study Completion Date	October 14, 2016
Actual Primary Completion Date	December 11, 2012 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Good general health; 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; Adequate contraception. For more information on this criterion can be found in the protocol. 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 that is 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, well-controlled asthma; Diabetes mellitus type 1 or 2; Thyroidectomy or thyroid disease in the12 months prior to study entry; Angioedema in the 3 years prior to study entry; 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 spleen; Individuals at high-risk of acquiring HIV infection; Presence of pre-existing neutralizing antibodies for Adenovirus 5 or 48; Pregnancy or breastfeeding
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 50 Years (Adult)
Accepts Healthy Volunteers	Yes
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00695877
Other Study ID Numbers ICMJE	Ad5HVR48.ENVA.01/IPCAVD-002; 10701 ( Registry Identifier: DAIDS ES Registry Number ); Ad5HVR48.ENVA.01/ IPCAVD-002
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	National Institute of Allergy and Infectious Diseases (NIAID)
Study Sponsor ICMJE	National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Chair: Lindsey Baden, MD Brigham and Women's Hospital Study Chair: Dan Barouch, MD Beth Israel Deaconess Medical Center
PRS Account	National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date	May 2018
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP