Safety of and Immune Response to an Investigational HIV-1 Vaccine With or Without Interleukin-12 (IL-12) in HIV-1 Infected Adults

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01266616
First received: December 23, 2010
Last updated: February 4, 2014
Last verified: February 2014
  Purpose

Therapeutic HIV vaccines are designed to control HIV infection by boosting the body's natural immune response. There are currently no FDA-approved therapeutic HIV vaccines. This study will test whether giving an HIV-1 vaccine together with or without interleukin 12 (IL-12) is safe and effective. This study will also test a new way of giving the vaccine called electroporation (EP).


Condition Intervention Phase
HIV Infections
Biological: Profectus HIV MAG pDNA vaccine
Biological: IL-12
Other: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase I Randomized, Partially Double-Blind, Placebo-Controlled, Dose-Escalation Study to Evaluate the Safety and Immunogenicity of a Cytokine Enhanced HIV-1 Multi-Antigen (HIV MAG) pDNA Vaccine Delivered Intramuscularly Followed by in Vivo Electroporation (IM/EP) or Intramuscularly in HIV-1 Infected Adults Receiving ART

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Occurrence of at least one greater than Grade 3 adverse event (AE) including signs/symptoms, lab toxicities, and/or clinical events that is possibly, probably, or definitely related to study treatment, as judged by the core team [ Time Frame: From the first day of study treatment until 28 days after the last study vaccine administration ] [ Designated as safety issue: Yes ]
  • Change in the number of interferon (IFN)-gamma generating (in response to gag) CD4 T cells/million peripheral blood mononuclear cells (PBMCs) as measured by intracellular cytokine staining (ICS) [ Time Frame: From Baseline to Week 14 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Answering "no" to the question, "In your opinion, would this study's vaccination procedure be acceptable as part of a treatment for HIV, if it proved to be effective?" [ Time Frame: From Week 0 to Week 36 ] [ Designated as safety issue: No ]
  • Answering "no" to the question, "In your opinion, would this study's vaccination procedure be acceptable if it could contribute to increased scientific knowledge about how best to administer vaccines to prevent or treat infections?" [ Time Frame: From Week 0 to Week 36 ] [ Designated as safety issue: No ]
  • Premature treatment discontinuation for reasons related to study treatment or related to any real or perceived effect of study vaccination or its administration [ Time Frame: From Week 0 to Week 36 ] [ Designated as safety issue: No ]
  • Rated pain (for participants administered vaccine/placebo by the EP device) [ Time Frame: When the device was placed on the skin and the vaccine/placebo was injected; at the time of the electrical stimulation and muscle contraction; and at 10 and 30 minutes after the procedure was completed at Weeks 0, 4, and 12 ] [ Designated as safety issue: No ]
  • Changes from baseline and absolute values of multiple functions of CD4 and CD8 T cells in response to gag and other vaccine-coded antigens individually and in sum [ Time Frame: At Week 8, Week 14, and possibly other time points depending on the first set of data in an ICS assay ] [ Designated as safety issue: No ]

Enrollment: 62
Study Start Date: March 2011
Study Completion Date: April 2013
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1: Vaccine alone IM/EP
HIV MAG pDNA alone IM/EP
Biological: Profectus HIV MAG pDNA vaccine
3,000 mcg admixture of two vaccine plasmids: ProfectusVax DNA Plasmid (HIV-1 gag/pol) and ProfectusVax DNA Plasmid (HIV-1 nef/tat/vif, env) at Weeks 0, 4, and 12
Placebo Comparator: Cohort 1: Placebo
Placebo given as an injection in each upper arm
Other: Placebo
Saline injections at Weeks 0, 4, and 12
Experimental: Cohort 2: Vaccine plus IL-12 IM/EP
HIV MAG pDNA plus 50 mcg of IL-12 pDNA IM/EP
Biological: Profectus HIV MAG pDNA vaccine
3,000 mcg admixture of two vaccine plasmids: ProfectusVax DNA Plasmid (HIV-1 gag/pol) and ProfectusVax DNA Plasmid (HIV-1 nef/tat/vif, env) at Weeks 0, 4, and 12
Biological: IL-12
Administered at Weeks 0, 4, and 12
Placebo Comparator: Cohort 2: Placebo
Placebo given as an injection in each upper arm
Other: Placebo
Saline injections at Weeks 0, 4, and 12
Experimental: Cohort 3: Vaccine plus IL-12 IM/EP
HIV MAG pDNA plus 250 mcg of IL-12 pDNA IM/EP
Biological: Profectus HIV MAG pDNA vaccine
3,000 mcg admixture of two vaccine plasmids: ProfectusVax DNA Plasmid (HIV-1 gag/pol) and ProfectusVax DNA Plasmid (HIV-1 nef/tat/vif, env) at Weeks 0, 4, and 12
Biological: IL-12
Administered at Weeks 0, 4, and 12
Placebo Comparator: Cohort 3: Placebo
Placebo given as an injection in each upper arm
Other: Placebo
Saline injections at Weeks 0, 4, and 12
Experimental: Cohort 4: Vaccine plus IL-12 IM/EP
HIV MAG pDNA plus 1,000 mcg of IL-12 pDNA IM/EP
Biological: Profectus HIV MAG pDNA vaccine
3,000 mcg admixture of two vaccine plasmids: ProfectusVax DNA Plasmid (HIV-1 gag/pol) and ProfectusVax DNA Plasmid (HIV-1 nef/tat/vif, env) at Weeks 0, 4, and 12
Biological: IL-12
Administered at Weeks 0, 4, and 12
Placebo Comparator: Cohort 4: Placebo
Placebo given as an injection in each upper arm
Other: Placebo
Saline injections at Weeks 0, 4, and 12
Experimental: Cohort 5: Vaccine plus IL-12 IM
HIV MAG pDNA plus 1,000 mcg (or highest dose reached) IL-12 pDNA IM
Biological: Profectus HIV MAG pDNA vaccine
3,000 mcg admixture of two vaccine plasmids: ProfectusVax DNA Plasmid (HIV-1 gag/pol) and ProfectusVax DNA Plasmid (HIV-1 nef/tat/vif, env) at Weeks 0, 4, and 12
Biological: IL-12
Administered at Weeks 0, 4, and 12
Placebo Comparator: Cohort 5: Placebo
Placebo given as an injection in each upper arm
Other: Placebo
Saline injections at Weeks 0, 4, and 12

Detailed Description:

Although highly active antiretroviral therapy (HAART) has greatly reduced HIV infection-related morbidity and mortality, individual response to therapy can be variable. Therapeutic vaccination works by augmenting virus-specific immunity and can be given with or without immunomodulatory agents or adjuvants. In conjunction with HAART, therapeutic vaccination may be a more effective treatment for the suppression of HIV-1 replication. This study will examine the safety and efficacy of giving an investigational vaccine with or without IL-12 in HIV-1 infected adults receiving HAART. This study will also test whether delivering the vaccine using EP is safe and increases the efficacy of the vaccine.

Participation in this study will last approximately 36 weeks. Participants will be randomly assigned to one of five cohorts. Cohort 1 will receive the HIV multi-antigen plasmid DNA (HIV MAG pDNA) vaccine or placebo intramuscularly (IM) in the upper arm followed by EP. Cohorts 2 through 4 will receive the HIV MAG pDNA vaccine and sequentially increasing doses of GENEVAX IL-12 pDNA or placebo by IM/EP. Cohort 5 will receive the HIV MAG pDNA vaccine with the highest dose of IL-12 pDNA or placebo by needle and syringe in the upper arm.

Participants receive two injections at Weeks 0, 4, and 12. Participants will complete a questionnaire that assesses the acceptability of the vaccine and remain at the clinic 30 minutes for observation after each vaccination. Participants will be contacted by telephone 2 to 3 days post-vaccination to assess vaccination-related signs and/or symptoms. All participants will be asked to record their temperatures and any symptoms they experience daily for 4 days following each vaccination on a Vaccination Report Card (VRC). All nonstudy vaccines or medications should also be recorded on the VRC. Study visits will occur at Weeks 0, 1, 2, 4, 5, 6, 8, 12, 13, 14, 16, 24, and 36. At most visits, participants will undergo a physical examination. Women of reproductive potential will also undergo pregnancy testing before receiving injections on Weeks 0, 4, and 12. Blood will be drawn at various time points to evaluate participants' health and measure immunologic markers, CD4 and CD8 T-cell counts, and cytokine levels. Blood and plasma will also be stored for future exploratory studies.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV-1 infected
  • Stable antiretroviral therapy (ART) for a minimum of 6 consecutive months prior to study entry and intention to remain on stable ART until study completion
  • CD4 T-cell count greater than or equal to 500 cells/mm3 (within 30 days prior to study entry)
  • At least two measurements of HIV-1 RNA levels less than or equal to 200 copies/mL (first measurement must be performed at least 6 months prior to study entry and second measurement must be performed between 6 months prior to study entry and at least 30 days prior to study entry)
  • Screening HIV-1 RNA less than 50 copies/mL (within 30 days prior to study entry)
  • Hepatitis B surface antigen negative (within 30 days prior to study entry)
  • Hepatitis C antibody negative or, if hepatitis C antibody positive, hepatitis C virus RNA negative (within 30 days prior to study entry)
  • Certain laboratory values obtained within 30 days prior to study entry; more information can be found in the protocol
  • Females of reproductive potential must have a negative urine pregnancy test within 3 days prior to study entry
  • All study participants participating in sexual activity that could lead to pregnancy must agree to use at least one of the following forms of birth control for at least 21 days prior to study entry until the final study visit:

    • Condoms (male or female) with or without a spermicidal agent
    • Diaphragm or cervical cap with spermicide
    • Intrauterine device (IUD)
    • Hormone-based contraceptive
  • Females who are not of reproductive potential are eligible without requiring the use of a contraceptive
  • Ability and willingness of subject to provide written informed consent
  • Collection of a pre-entry PBMC specimen for immunologic assays and entered into the Laboratory Data Management System (LDMS)

Exclusion Criteria:

  • Confirmed (defined as two consecutive values) CD4 T-cell count less than 200 cells/mm3 at any time or any history or subject recollection of CD4 T-cell count less than 200 cells/mm3 prior to screening
  • Any active malignancy that may require chemotherapy or radiation therapy
  • Bleeding diathesis or condition associated with prolonged bleeding time that would contraindicate IM injection
  • A skin-fold measurement of the cutaneous and subcutaneous tissue for eligible injection sites (on the medial deltoid muscles) that exceeds 40 mm
  • Use of immunomodulatory, cytokine, or growth stimulating factors such as systemic corticosteroids, cyclosporine, methotrexate, azathioprine, anti-CD25 antibody, granulocyte macrophage colony-stimulating factor (GM-CSF), chondrocyte colony-stimulating factor (C-CSF), IFN, or interleukin-2 (IL-2) (within 30 days prior to study entry)
  • Pregnancy or breastfeeding
  • Use of any prior HIV vaccine (prophylactic and/or therapeutic) within 1 year before study entry
  • Use of any investigational treatment within 6 months before study entry
  • Use of any licensed or experimental non-HIV vaccination (e.g., hepatitis B, influenza, pneumococcal polysaccharide) within 4 weeks prior to study entry
  • Use of any infusion blood product or immune globulin within 3 months prior to study entry
  • Known or suspected hypersensitivity to any vaccine component, including hypersensitivity to amide-type local anesthetics, such as lidocaine (Xylocaine), mepivacaine (Polocaine/Carbocaine), etidocaine (Duranest), bupivacaine (Marcaine), or prilocaine
  • Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements
  • Serious illness requiring systemic treatment and/or hospitalization within 7 days prior to study entry
  • Current use of any electronic stimulation device, such as cardiac demand pacemakers, automatic implantable cardiac defibrillators, nerve stimulators, or deep brain stimulators
  • History of cardiac arrhythmia or palpitations (e.g., supraventricular tachycardia, atrial fibrillation, frequent ectopy, or sinus bradycardia [i.e., <50 beats per minute on exam]) prior to study entry (NOTE: Sinus arrhythmia is not excluded)
  • History of syncope or fainting episode within 1 year of study entry
  • Seizure disorder or any history of prior seizure
  • Extensive tattoos covering the site of administration (upper left and right medial deltoid muscles)
  • Presence of any surgical or traumatic metal implants at the site of administration (medial deltoid muscles)
  • Any chronic inflammatory disease (e.g., ankylosing spondylitis, psoriasis, inflammatory bowel disease)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01266616

Locations
United States, California
UCLA CARE Center CRS
Los Angeles, California, United States, 90035
Stanford AIDS Clinical Trials Unit CRS
Palo Alto, California, United States, 94304-5350
Ucsf Hiv/Aids Crs
San Francisco, California, United States, 94110
United States, Colorado
University of Colorado Hospital CRS
Aurora, Colorado, United States, 80045
United States, Massachusetts
Massachusetts General Hospital Clinical Research Site (MGH CRS) CRS
Boston, Massachusetts, United States, 02114
Brigham and Women's Hospital Therapeutics Clinical Research Site (BWH TCRS) CRS
Boston, Massachusetts, United States, 02115
United States, Missouri
Washington University Therapeutics (WT) CRS
St. Louis, Missouri, United States, 63110
United States, New York
Univ. of Rochester ACTG CRS
Rochester, New York, United States, 14642
Trillium Health ACTG CRS
Rochester, New York, United States, 14607
United States, Ohio
Cincinnati CRS
Cincinnati, Ohio, United States, 45219
United States, Pennsylvania
Penn Therapeutics Crs
Philadelphia, Pennsylvania, United States, 19104
University of Pittsburgh CRS
Pittsburgh, Pennsylvania, United States, 15213-2582
United States, Texas
Houston AIDS Research Team CRS
Houston, Texas, United States, 77030
Sponsors and Collaborators
Investigators
Study Chair: Jeffrey Jacobson, MD Division of Infectious Diseases and HIV Medicine, Drexel University College of Medicine
  More Information

Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01266616     History of Changes
Other Study ID Numbers: A5281, 10846
Study First Received: December 23, 2010
Last Updated: February 4, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Interleukin-12
Electroporation
HIV Therapeutic Vaccine

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Interleukin-12
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Adjuvants, Immunologic
Immunologic Factors

ClinicalTrials.gov processed this record on April 22, 2014