Safety and Immunogenicity of pDNA Vaccines Expressing HIV M Group p24^Gag Conserved Elements and/or p55^Gag, Administered With IL-12 pDNA
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: p24CE1/2 pDNA Vaccine; p55^gag pDNA Vaccine; IL-12 pDNA Adjuvant; Placebo; Ichor Medical Systems Intramuscular TriGrid Delivery System (TDS-IM) electroporation (EP) device
Intervention description: Administered bilaterally using the Ichor Medical Systems Intramuscular TriGrid Delivery System (TDS-IM) electroporation (EP) device; Administered bilaterally using the TDS-IM EP device; Administered bilaterally using the TDS-IM EP device; Administered bilaterally using the TDS-IM EP device; The TDS-IM EP device will be used to administer study product(s).
Intervention MeSH terms: Interleukin-12; Vaccines
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 56.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: HIV vaccine; DNA vaccine; IL-12; Electroporation; p24; Gag; Adjuvant; Healthy

Summary:

      The purpose of this study is to evaluate the safety, tolerability, and immunogenicity of two
      HIV-1 pDNA vaccines: p24CE1/2 pDNA and p55^gag pDNA administered with IL-12 pDNA adjuvant,
      given by intramuscular (IM) injection with electroporation (EP), in healthy, HIV-uninfected
      adults.
    

Eligibility criteria:

        Inclusion Criteria:

        General and Demographic Criteria

          -  Age of 18 to 50 years

          -  Access to a participating HIV Vaccine Trials Network (HVTN) clinical research site
             (CRS) and willingness to be followed for the planned duration of the study

          -  Agrees not to enroll in another study of an investigational research agent prior to
             completion of last required protocol visit (excludes annual health contact visit)

          -  Good general health as shown by medical history, physical exam, and screening
             laboratory tests

        HIV-Related Criteria:

          -  Assessed by the clinic staff as being at "low risk" for HIV infection and committed to
             maintaining behavior consistent with low risk of HIV exposure through the last
             required protocol clinic visit.

        Laboratory Inclusion Values

          -  Hemoglobin greater than or equal to 11.0 g/dL for volunteers who were born female,
             greater than or equal to 13.0 g/dL for volunteers who were born male

          -  White blood cell count equal to 3,300 to 12,000 cells/mm^3

          -  Total lymphocyte count greater than or equal to 800 cells/mm^3

          -  Remaining differential either within institutional normal range or with site physician
             approval

          -  Platelets equal to 125,000 to 550,000/mm^3

          -  Chemistry panel: alanine aminotransferase (ALT), aspartate aminotransferase (AST), and
             alkaline phosphatase less than 1.25 times the institutional upper limit of normal;
             creatine phosphokinase (CPK) less than or equal to 2.0 times the institutional upper
             limit of normal; creatinine less than or equal to institutional upper limit of normal.

        Virology

          -  Negative HIV-1 and -2 blood test: U.S. volunteers must have a negative Food and Drug
             Administration (FDA)-approved enzyme immunoassay (EIA).

          -  Negative Hepatitis B surface antigen (HBsAg)

          -  Negative anti-Hepatitis C virus antibodies (anti-HCV), or negative HCV polymerase
             chain reaction (PCR) if the anti-HCV is positive

          -  Normal urine:

               -  Negative urine glucose, and

               -  Negative or trace urine protein, and

               -  Negative or trace urine hemoglobin

        Reproductive Status

          -  Reproductive status: A volunteer who was born female must:

               -  Agree to consistently use effective contraception for sexual activity that could
                  lead to pregnancy from at least 21 days prior to enrollment through the last
                  required protocol clinic visit.

               -  Or not be of reproductive potential, such as having reached menopause (no menses
                  for 1 year) or having undergone hysterectomy, bilateral oophorectomy, or tubal
                  ligation;

               -  Or be sexually abstinent.

        Exclusion Criteria:

        General

          -  Allergy to amide-type local anesthetics (bupivacaine [Marcaine], lidocaine
             [Xylocaine], mepivacaine [Polocaine/Carbocaine], etidocaine [Duranest], prilocaine
             [Citanest, EMLA® cream])

          -  Investigational research agents received within 30 days before first vaccination

          -  Body mass index (BMI) greater than or equal to 40; or BMI greater than or equal to 35
             with 2 or more of the following: age greater than 45, systolic blood pressure greater
             than 140 mm Hg, diastolic blood pressure greater than 90 mm Hg, current smoker, known
             hyperlipidemia

          -  Intent to participate in another study of an investigational research agent or any
             other study that requires non-HVTN HIV antibody testing during the planned duration of
             the study

          -  Pregnant or breastfeeding

          -  Active duty and reserve U.S. military personnel

        Vaccines and other Injections

          -  HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received
             control/placebo in an HIV vaccine trial, the HVTN Protocol Safety Review Team (PSRT)
             will determine eligibility on a case-by-case basis.

          -  Previous receipt of monoclonal antibodies (mAbs), whether licensed or investigational;
             the HVTN 119 PSRT will determine eligibility on a case-by-case basis.

          -  Non-HIV experimental vaccine(s) received within the last 5 years in a prior vaccine
             trial.

        Immune System

          -  Immunosuppressive medications received within 168 days before first vaccination.

          -  Serious adverse reactions to vaccines or to vaccine components

          -  Autoimmune disease

          -  Immunodeficiency

        Clinically significant medical conditions

          -  Untreated or incompletely treated syphilis infection

          -  Clinically significant medical condition, physical examination findings, clinically
             significant abnormal laboratory results, or past medical history with clinically
             significant implications for current health.

          -  Any medical, psychiatric, occupational, or other condition that, in the judgment of
             the investigator, would interfere with, or serve as a contraindication to, protocol
             adherence, assessment of safety or reactogenicity, or a volunteer's ability to give
             informed consent

          -  Psychiatric condition that precludes compliance with the protocol. Specifically
             excluded are persons with psychoses within the past 3 years, ongoing risk for suicide,
             or history of suicide attempt or gesture within the past 3 years.

          -  Current anti-tuberculosis (TB) prophylaxis or therapy

          -  Asthma exclusion criteria: Asthma other than mild, well-controlled asthma.

          -  Diabetes mellitus type 1 or type 2, including cases controlled with diet alone. (Not
             excluded: history of isolated gestational diabetes.)

          -  Thyroidectomy, or thyroid disease requiring medication during the last 12 months

          -  Hypertension

          -  Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or
             platelet disorder requiring special precautions)

          -  Malignancy

          -  Seizure disorder

          -  Asplenia

          -  History of hereditary angioedema, acquired angioedema, or idiopathic angioedema.

          -  Presence of implanted electronic medical device (e.g., cochlear implant, pacemaker,
             implantable cardioverter defibrillator)

          -  Presence of surgical or traumatic metal implant at the intended site of administration
             (including the deltoid muscles and/or overlying skin)

          -  Sinus bradycardia (defined as less than 50 beats per minute (bpm) on exam) or a
             history of cardiac arrhythmia: e.g., supraventricular tachycardia, atrial
             fibrillation, or frequent ectopy. NOTE: Sinus arrhythmia is not excluded.