Clinical trial NCT00141024: Safety of and Immune Response to the Experimental Preventive HIV Vaccine, EP HIV-1090, in Healthy, HIV-1 Uninfected Adults
Official title: A Phase I Clinical Trial to Evaluate the Safety and Immunogenicity of the Recombinant Protein Vaccine EP-1043 and the DNA Vaccine EP HIV-1090 Given Alone or in Combination in Healthy, HIV-1-Uninfected Adult Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: HIV Seronegativity
HIV Preventive Vaccine
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2005-09-01
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of the study is to determine the safety of and immune response to the investigational HIV vaccine, EP HIV-1090, in HIV uninfected adults.

Detailed description: The worldwide HIV/AIDS epidemic may only be controlled through the development of a safe and effective vaccine that will prevent HIV infection. DNA vaccines are inexpensive to construct, readily produced in large quantities, and stable for long periods of time. EP HIV-1090 is a DNA HIV CTL vaccine; the proteins for which its genes code are designed to interact with CD8 cells (CTL) and cause CD8 cell proliferation. The DNA plasmids in EP HIV-1090 code for proteins conserved among HIV subtypes A, B, C, D, F, and G, which encompass the HLA subtypes of 85% of the worldwide general population.

Participants will be enrolled in this study for 1 year. Group 4 participants will receive EP HIV-1090 or placebo at study entry and Months 1, 3, and 6. There will be 11 study visits that will occur at screening; study entry; and Months 0.5, 1, 1.5, 3, 3.5, 6, 6.5, 9, and 12. A physical exam and risk reduction/pregnancy prevention counseling will occur at each visit. Participants will be asked about their adverse experiences from vaccination at each visit. Blood and urine collection will occur at selected visits.

Eligibility criteria: Note: Groups 1, 2, 3, and 5 have permanently discontinued enrollment per the 12/26/06 letter of amendment.

Inclusion Criteria:

* Good general health
* Have access to a participating HIV Vaccine Trials Unit (HVTU) and are willing to be followed for the duration of the study
* Willing to receive HIV test results
* Have understanding of the study
* Willing to use acceptable forms of contraception
* Negative pregnancy test

Exclusion Criteria:

* HIV vaccines in a prior HIV vaccine trial
* Immunosuppressive medications within 168 days prior to first vaccination
* Blood products within 120 days prior to first vaccination
* Immunoglobulin within 60 days prior to first vaccination
* Live attenuated vaccines within 30 days prior to first vaccination
* Investigational research agents within 30 days prior to first vaccination
* Medically indicated subunit or killed vaccines within 14 days prior to first study vaccine administration, or allergy treatment with antigen injections within 30 days prior to first vaccination
* Current tuberculosis prophylaxis or therapy
* Clinically significant medical condition, abnormal physical exam findings, abnormal laboratory results, or past medical history that may affect current health
* Any medical, psychiatric, or social condition that would interfere with the study. More information about this criterion can be found in the protocol.
* Any job-related responsibility that would interfere with the study
* Serious adverse reaction to vaccines. A person who had an adverse reaction to pertussis vaccine as a child is not excluded.
* Autoimmune disease or immunodeficiency
* Active syphilis infection unless the participant has completed full treatment for syphilis 6 months prior to enrollment
* Unstable asthma
* Diabetes mellitus type 1 or 2
* Thyroid disease or thyroidectomy requiring treatment
* Serious angioedema within 3 years prior to enrollment
* Uncontrolled hypertension
* Body mass index (BMI) of 40 or greater
* BMI of 35 or greater if the participant is older than 45 years, has systolic blood pressure greater than 140 mm Hg, has diastolic blood pressure greater than 90 mm Hg, smokes, or has known hyperlipidemia
* 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 requiring medication within the 3 years prior to enrollment
* Absence of the spleen
* Mental illness that would interfere with the study
* Other conditions that, in the judgment of the investigator, would interfere with the study
* Pregnancy, breastfeeding, or plans to become pregnant

Primary outcomes:
measure: Safety as assessed by local and systemic reactogenicity signs and symptoms, laboratory measures, and adverse and serious experiences
timeFrame: After each injection and for 12 months following the first injection
Secondary outcomes:
measure: Immunogenicity as assessed by HIV-specific cellular responses assessed by interferon-gamma ELISpot assays and intracellular cytokine staining
timeFrame: Throughout the study
measure: Social impacts as assessed by negative experiences or problems reported by the participants
timeFrame: Throughout the study
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: San Francisco Vaccine and Prevention CRS
state: California
city: Baltimore
country: United States
facility: Project Brave HIV Vaccine CRS
state: Maryland
city: Rochester
country: United States
facility: Univ. of Rochester HVTN CRS
state: New York
Study officials:
affiliation: University of Rochester
name: Xia Jin, MD, PhD
role: STUDY_CHAIR
affiliation: Asociación Civil Impacta Salud y Educación (IMPACTA)
name: Jorge Sanchez, MD
role: STUDY_CHAIR
References:
citation: Esparza J, Osmanov S. HIV vaccines: a global perspective. Curr Mol Med. 2003 May;3(3):183-93. doi: 10.2174/1566524033479825.
citation: Gaschen B, Taylor J, Yusim K, Foley B, Gao F, Lang D, Novitsky V, Haynes B, Hahn BH, Bhattacharya T, Korber B. Diversity considerations in HIV-1 vaccine selection. Science. 2002 Jun 28;296(5577):2354-60. doi: 10.1126/science.1070441.
citation: Livingston BD, Newman M, Crimi C, McKinney D, Chesnut R, Sette A. Optimization of epitope processing enhances immunogenicity of multiepitope DNA vaccines. Vaccine. 2001 Sep 14;19(32):4652-60. doi: 10.1016/s0264-410x(01)00233-x.
citation: McKinney DM, Skvoretz R, Livingston BD, Wilson CC, Anders M, Chesnut RW, Sette A, Essex M, Novitsky V, Newman MJ. Recognition of variant HIV-1 epitopes from diverse viral subtypes by vaccine-induced CTL. J Immunol. 2004 Aug 1;173(3):1941-50. doi: 10.4049/jimmunol.173.3.1941.
citation: Wilson CC, McKinney D, Anders M, MaWhinney S, Forster J, Crimi C, Southwood S, Sette A, Chesnut R, Newman MJ, Livingston BD. Development of a DNA vaccine designed to induce cytotoxic T lymphocyte responses to multiple conserved epitopes in HIV-1. J Immunol. 2003 Nov 15;171(10):5611-23. doi: 10.4049/jimmunol.171.10.5611.
citation: Jin X, Morgan C, Yu X, DeRosa S, Tomaras GD, Montefiori DC, Kublin J, Corey L, Keefer MC; NIAID HIV Vaccine Trials Network. Multiple factors affect immunogenicity of DNA plasmid HIV vaccines in human clinical trials. Vaccine. 2015 May 11;33(20):2347-53. doi: 10.1016/j.vaccine.2015.03.036. Epub 2015 Mar 25.