Safety and Effectiveness of PENNVAX-B Vaccine Alone, With Il-12, or IL-15 in Healthy Adults

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00528489

Collaborator

HIV Vaccine Trials Network (Other)

120

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Biological: PennVax B Biological: IL-12 Biological: IL-15	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

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 Start Date :

Oct 1, 2007

Actual Primary Completion Date :

Jan 1, 2010

Actual Study Completion Date :

Jan 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 PENNVAX-B with 0.8 mg IL-15 administered in both deltoids at Months 0, 1, 3, and 6	Biological: PennVax B DNA vaccine containing the HIV genes Gag, Pol, and Env Biological: IL-15 Cytokine injection
Experimental: 2 PENNVAX-B administered alone in both deltoids at Months 0, 1, 3, and 6	Biological: PennVax B DNA vaccine containing the HIV genes Gag, Pol, and Env
Experimental: 3 PENNVAX-B administered alone in both deltoids at Months 0, 1, 3, and 6	Biological: PennVax B DNA vaccine containing the HIV genes Gag, Pol, and Env Biological: IL-12 Cytokine injection
Experimental: 4 PENNVAX-B with 2 mg IL-15 injected into both deltoids at Months 0, 1, 3, and 6	Biological: PennVax B DNA vaccine containing the HIV genes Gag, Pol, and Env Biological: IL-15 Cytokine injection

Outcome Measures

Primary Outcome Measures

Safety data including local and systemic reactogenicity sign and symptoms, laboratory measures of safety, and adverse and serious adverse events [Throughout study]
Safety data from Groups 1 and 4 [Throughout study]

Secondary Outcome Measures

HIV-1 specific interferon gamma ELISpot and/or intracellular cytokine staining T cell response [2 weeks after 3rd and 4th vaccinations]
HIV-1 specific neutralizing and binding antibody assays [2 weeks after 3rd and 4th vaccinations]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alabama Vaccine CRS	Birmingham	Alabama	United States	35294
2	San Francisco Vaccine and Prevention CRS	San Francisco	California	United States
3	Brigham and Women's Hosp. CRS	Boston	Massachusetts	United States
4	NY Blood Ctr./Bronx CRS	Bronx	New York	United States	10456
5	NY Blood Ctr./Union Square CRS	New York	New York	United States	10003
6	HIV Prevention & Treatment CRS	New York	New York	United States	10032
7	3535 Market Street CRS	Philadelphia	Pennsylvania	United States
8	Vanderbilt Vaccine CRS	Nashville	Tennessee	United States