Clinical trial NCT00528489: Safety and Effectiveness of PENNVAX-B Vaccine Alone, With Il-12, or IL-15 in Healthy Adults
Official title: A Phase I Clinical Trial to Evaluate the Safety and Immunogenicity of PENNVAX-B (Gag, Pol, Env) Given Alone, With IL-12 DNA, or With a Dose Escalation of IL-15 DNA, in Healthy, HIV-1-uninfected Adults Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: HIV Seronegativity
DNA Plasmid Vaccine
HIV Preventive Vaccine
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: HIV Vaccine Trials Network
First posted: 2007-09-12
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, tolerability, and immune response to the DNA HIV vaccine, PENNVAX-B alone, in combination with IL-12, or with 2 different doses of IL-15.

Detailed description: A vaccine that is effective against multiple strains of HIV remains the best option for preventing the spread of HIV. Plasmid DNA vaccines are inexpensive and easy to construct. When DNA vaccines are administered in combination with cytokines, such as IL-12 or IL-15, the immune response to the vaccine is increased. The purpose of this study is to determine the safety and tolerability of the DNA plasmid vaccine, PENNVAX-B when administered alone, or with IL-12 or IL-15 DNA adjuvants. The most effective and safe dose of IL-15 will also be determined during this study.

This study will last approximately 12 months. Participants will be randomly assigned to one of four groups. Group 1 will receive an injection of PENNVAX-B combined with 0.8 mg IL-15 in each deltoid or placebo. Group 2 will receive an injection of PENNVAX-B alone or placebo. Group 3 will receive an injection of PENNVAX-B combined with IL-12 in each deltoid or placebo. Group 4 will receive PENNVAX-B combined with 2 mg IL-15 or placebo. Injections will occur at study entry, Months 1, 3, and 6. Additional study visits will occur on Days 14, 42, 98, 182, 273, and 364. At these visits a brief physical, blood collection, interview, and risk reduction counseling will occur. At some visits HIV testing, urine collection, and pregnancy tests will also occur.

As of 05/30/08, participants will be enrolled into Groups 3 and 4 at a limited pace to allow for additional safety reviews for the first few participants in these groups. Additionally, safety data will be reviewed for Groups 1 and 2 to determine whether the remainder of participants in Groups 2, 3, and 4 will be enrolled.

Eligibility criteria: Inclusion Criteria:

* HIV-1 and -2 uninfected
* Willing to receive HIV test results
* Good general health
* Certain laboratory values within normal range or with site physician approval
* Negative for Hepatitis B surface antigen
* Negative Hepatitis C test
* Willing to use acceptable methods of contraception

Exclusion Criteria:

* HIV vaccines or placebos in prior HIV trial. Participants who can provide documentation that they received a placebo in a prior HIV trial may be eligible.
* Immunosuppressive medications within 168 days prior to first study vaccination. Participants using corticosteroid nasal spray for allergies or topical corticosteroids for mild, uncomplicated dermatitis are not excluded.
* Blood products within 120 days prior to first study vaccination
* Receipt of immunoglobulin within 60 days prior to first vaccination
* Live attenuated vaccines within 30 days prior to first study vaccination
* Any vaccine that is not a live attenuated vaccine within 14 days prior to first study vaccination
* Investigational research agents within 60 days prior to first study vaccination
* Current anti-tuberculosis (TB) preventive therapy or treatment clinically significant medical condition, abnormal physical exam findings, abnormal laboratory results, or past medical history that may affect current health. More information about this criterion can be found in the protocol.
* Any medical, psychiatric, social, occupational, or other condition or responsibility that in the opinion of the investigator would interfere with the study. More information about this criterion can be found in the protocol.
* Allergy to amide-type local anesthetics
* Serious adverse reactions to vaccines
* Autoimmune disease or immunodeficiency
* Active syphilis infection. Participants who have been fully treated for syphilis over 6 months prior to study entry are not excluded.
* Asthma other than mild, well-controlled asthma. More information on this criterion can be found in the protocol.
* Type 1 or type 2 diabetes mellitus. Participants with histories of isolated gestational diabetes are not excluded.
* Thyroidectomy or thyroid disease requiring medication during the 12 months prior to study entry
* Accumulation of fluid in the blood vessels (angioedema) within 3 years prior to study entry if episodes are considered serious or have required medication in the 2 years prior to study entry
* Uncontrolled hypertension
* Body Mass Index of 40 or greater OR of 35 or greater if certain other criteria apply. More information about these criteria can be found in the protocol
* Bleeding disorder
* Cancer. Participants with surgically removed cancer that is unlikely to recur are not excluded.
* Seizure disorder
* Absence of the spleen
* Pregnancy or breastfeeding

Primary outcomes:
measure: Safety data including local and systemic reactogenicity sign and symptoms, laboratory measures of safety, and adverse and serious adverse events
timeFrame: Throughout study
measure: Safety data from Groups 1 and 4
timeFrame: Throughout study
Secondary outcomes:
measure: HIV-1 specific interferon gamma ELISpot and/or intracellular cytokine staining T cell response
timeFrame: 2 weeks after 3rd and 4th vaccinations
measure: HIV-1 specific neutralizing and binding antibody assays
timeFrame: 2 weeks after 3rd and 4th vaccinations
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Vaccine CRS
state: Alabama
city: San Francisco
country: United States
facility: San Francisco Vaccine and Prevention CRS
state: California
city: Boston
country: United States
facility: Brigham and Women's Hosp. CRS
state: Massachusetts
city: Bronx
country: United States
facility: NY Blood Ctr./Bronx CRS
state: New York
city: New York
country: United States
facility: NY Blood Ctr./Union Square CRS
state: New York
city: New York
country: United States
facility: HIV Prevention & Treatment CRS
state: New York
city: Philadelphia
country: United States
facility: 3535 Market Street CRS
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt Vaccine CRS
state: Tennessee
Study officials:
affiliation: HVTN, FHCRC
name: Scott Parker, MD
role: STUDY_CHAIR
References:
citation: Johnston MI, Fauci AS. An HIV vaccine--evolving concepts. N Engl J Med. 2007 May 17;356(20):2073-81. doi: 10.1056/NEJMra066267. No abstract available.
citation: Ogawa H, Ueno M, Uchibori H, Matsumoto I, Seno N. Direct carbohydrate analysis of glycoproteins electroblotted onto polyvinylidene difluoride membrane from sodium dodecyl sulfate-polyacrylamide gel. Anal Biochem. 1990 Nov 1;190(2):165-9. doi: 10.1016/0003-2697(90)90175-9.
citation: McBurney SP, Ross TM. Developing broadly reactive HIV-1/AIDS vaccines: a review of polyvalent and centralized HIV-1 vaccines. Curr Pharm Des. 2007;13(19):1957-64. doi: 10.2174/138161207781039841.
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.