Clinical trial NCT00301184: Safety of and Immune Response to a DNA HIV Vaccine (pGA2/JS7) Boosted With a Modified Vaccinia HIV Vaccine (MVA/HIV62) in Healthy Adults
Official title: A Phase I Clinical Trial to Evaluate the Safety and Immunogenicity of pGA2/JS7 DNA Vaccine and Recombinant Modified Vaccinia Ankara/HIV62 Vaccine in Healthy, HIV-1-Uninfected Adult Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: HIV Seronegativity
HIV Preventive Vaccine
HIV DNA Vaccine
Modified Vaccinia Ankara Vaccine
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: HIV Vaccine Trials Network
First posted: 2006-03-10
Enrollment: 120
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 this study is to determine the safety of and immune response to a DNA HIV vaccine, pGA2/JS7, followed by a modified vaccinia (smallpox) HIV vaccine, MVA/HIV62, in HIV uninfected adults.

Detailed description: The worldwide HIV/AIDS epidemic may only be controlled through a safe and effective vaccine that will prevent HIV infection. DNA vaccines are inexpensive to construct, easily produced in large quantities, and stable for long periods of time. Recombinant modified vaccinia Ankara vaccines have been shown to be safe in humans, and immunogenicity after administration of both vaccines has been encouraging. When used together, a more robust immunologic response was associated with DNA HIV vaccine administration followed by modified vaccinia vaccine administration, compared to using either DNA or vaccinia vaccine alone. This study will evaluate the safety and immunogenicity of an experimental DNA HIV vaccine prime, pGA/JS7, followed by a similarly structured modified vaccinia boost, MVA/HIV62, in HIV uninfected adults. Participants in this study will be recruited only in the United States.

This study will be divided into 2 parts. Each participant will be involved with their part of study for 1 year. Participants in Part 1 will be randomly assigned to one of two different vaccination groups. Group 1A participants will be randomly assigned to receive either placebo or 2 lower doses of the DNA HIV vaccine (DNA) at study entry and Month 2, followed by 2 lower doses of the modified vaccinia vaccine (MVA) at Months 4 and 6. Group 1B will not enroll until safety and immunogenicity data from Group 1A have been evaluated. Group 1B participants will receive either placebo or two higher doses of DNA at study entry and Month 2, followed by two higher doses of MVA at Months 4 and 6.

Enrollment into Part 2 will begin only after safety data from Part 1 are reviewed. In Part 2, participants will be randomly assigned to one of two different vaccination groups. Within each group, participants will be randomly assigned to receive some series of vaccines or placebo. Group 2A participants will receive either placebo or the maximum tolerated dose (MTD) from Part 1 of DNA at study entry and MTD of MVA at Months 2 and 6. Group 2B participants will receive MTD of MVA at study entry and Months 2 and 6.

There will be 12 study visits over 12 months for Groups 1 and 2. There will be 11 study visits over 12 months for Groups 3 and 4. Medication history, a physical exam, an interview, HIV and pregnancy prevention counseling, and adverse events reporting will occur at all visits. Blood and urine collection and an electrocardiogram (ECG) will occur at selected visits.

Eligibility criteria: Inclusion Criteria:

* HIV uninfected
* Has access to a participating HIV Vaccine Trials Unit (HVTU) and is willing to be followed for the duration of the study
* Understands vaccination procedure
* Willing to receive HIV test results
* Good general health
* Willing to use acceptable forms of contraception

Exclusion Criteria:

* Received HIV vaccines in prior HIV vaccine trial
* Received vaccinia vaccine. More information on this criterion can be found in the protocol.
* Recreational cocaine or methamphetamine use within 12 months prior to study entry
* Immunosuppressive medications within 168 days prior to first study vaccine administration. Participants who use corticosteroid nasal spray for allergic rhinitis or topical corticosteroids for mild, uncomplicated dermatitis are not excluded.
* Blood products within 120 days prior to first study vaccine administration
* Immunoglobulin within 60 days prior to first study vaccine administration
* Live attenuated vaccines within 30 days prior to first study vaccine administration
* Investigational research agents within 30 days prior to first study vaccine administration
* Subunit or killed vaccines within 14 days (for influenza or pneumococcal vaccines) or 30 days (for allergy treatment with antigen injections) prior to first study vaccine administration
* 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
* Allergy to egg products
* Serious adverse reaction to vaccines. A person who had an adverse reaction to pertussis vaccine as a child is not excluded.
* History of or known active cardiac disease. More information on this criterion can be found in the protocol.
* Electrocardiogram (ECG) with clinically significant findings OR features that would interfere with assessments for myocarditis or pericarditis. More information on this criterion can be found in the protocol.
* Two or more of the following cardiac risk factors: elevated blood cholesterol (defined as fasting low density lipoprotein \[LDL\] of greater than 160 mg/dl); first-degree relative (e.g., mother, father, brother, sister) who had coronary artery disease before the age of 50; current smoker; or body mass index (BMI) greater than 35
* Autoimmune disease or immunodeficiency
* Active syphilis infection. Participants whose syphilis infection was fully treated at least 6 months prior to study entry are not excluded.
* Severe and unstable asthma
* Diabetes mellitus type 1 or 2
* Thyroid disease requiring treatment
* Serious angioedema within the past 2 years
* Uncontrolled hypertension OR systolic blood pressure (BP) of 150 mmHg or greater or diastolic BP of 100 mmHg or greater
* BMI greater than 40
* Bleeding disorder
* Cancer. If a participant has had surgery to remove the cancer and, in the opinion of the investigator, the cancer is not likely to recur during the study period, the participant is not excluded.
* Seizure disorder
* Asplenia
* Mental illness that would interfere with compliance with the protocol
* Other conditions that, in the judgment of the investigator, would interfere with the study
* Pregnancy or breastfeeding, or plans to become pregnant

Primary outcomes:
measure: Safety (local and systemic reactogenicity signs and symptoms, laboratory measures, and adverse and serious experiences)
timeFrame: Throughout study
measure: Immunogenicity, as defined by the protocol
timeFrame: Throughout study
measure: Social impacts (negative experiences or problems reported by the participants)
timeFrame: Throughout study
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Vaccine CRS
state: Alabama
city: Baltimore
country: United States
facility: Project Brave HIV Vaccine CRS
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hosp. CRS
state: Massachusetts
city: Saint Louis
country: United States
facility: Saint Louis Univ. School of Medicine, HVTU
state: Missouri
city: Rochester
country: United States
facility: Univ. of Rochester HVTN CRS
state: New York
city: Nashville
country: United States
facility: Vanderbilt Vaccine CRS
state: Tennessee
Study officials:
affiliation: University of Alabama at Birmingham
name: Paul Goepfert, MD
role: STUDY_CHAIR
affiliation: University of Rochester
name: Christine Mhorag Hay, MD
role: STUDY_CHAIR
References:
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citation: Smith JM, Amara RR, Campbell D, Xu Y, Patel M, Sharma S, Butera ST, Ellenberger DL, Yi H, Chennareddi L, Herndon JG, Wyatt LS, Montefiori D, Moss B, McClure HM, Robinson HL. DNA/MVA vaccine for HIV type 1: effects of codon-optimization and the expression of aggregates or virus-like particles on the immunogenicity of the DNA prime. AIDS Res Hum Retroviruses. 2004 Dec;20(12):1335-47. doi: 10.1089/aid.2004.20.1335.
citation: Sutter G, Staib C. Vaccinia vectors as candidate vaccines: the development of modified vaccinia virus Ankara for antigen delivery. Curr Drug Targets Infect Disord. 2003 Sep;3(3):263-71. doi: 10.2174/1568005033481123.
citation: Goepfert PA, Elizaga ML, Sato A, Qin L, Cardinali M, Hay CM, Hural J, DeRosa SC, DeFawe OD, Tomaras GD, Montefiori DC, Xu Y, Lai L, Kalams SA, Baden LR, Frey SE, Blattner WA, Wyatt LS, Moss B, Robinson HL; National Institute of Allergy and Infectious Diseases HIV Vaccine Trials Network. Phase 1 safety and immunogenicity testing of DNA and recombinant modified vaccinia Ankara vaccines expressing HIV-1 virus-like particles. J Infect Dis. 2011 Mar 1;203(5):610-9. doi: 10.1093/infdis/jiq105. Epub 2011 Jan 31.
citation: Elizaga ML, Vasan S, Marovich MA, Sato AH, Lawrence DN, Chaitman BR, Frey SE, Keefer MC; MVA Cardiac Safety Working Group. Prospective surveillance for cardiac adverse events in healthy adults receiving modified vaccinia Ankara vaccines: a systematic review. PLoS One. 2013;8(1):e54407. doi: 10.1371/journal.pone.0054407. Epub 2013 Jan 17.