Trial record 12 of 34 for:    " September 17, 2008":" October 17, 2008"[FIRST-RECEIVED-DATE]AND HIV[CONDITION]

PENNVAX-B With or Without IL-12 or IL-15 as a DNA Vaccine for HIV Infection

This study has been completed.
Sponsor:
Collaborator:
Drexel University
Information provided by:
University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT00775424
First received: October 17, 2008
Last updated: June 18, 2010
Last verified: June 2010
  Purpose

A phase Ib partially blinded pilot study to evaluate the safety and immunological effects of PENNVAX-B with or without co-administration of constructs containing DNA encoding for the expression of either IL-12 or IL-15.

Primary objectives

  1. To determine the safety of HIV-1 DNA constructs (PENNVAX-B).
  2. To determine the safety and optimal doses of the IL-12 and the IL-15 adjuvant constructs when given with PENNVAX-B.

Secondary objectives

  1. To compare the various vaccine groups for their immunological responses to several HIV-1 antigens, utilizing the ELISPOT assay.
  2. To analyze antibody responses to the vaccine antigens over time.
  3. To measure CD8 cell proliferative responses to vaccine antigens over time.

Condition Intervention Phase
HIV Infection
Biological: PENNVAX-B
Biological: GENEVAX IL-12-4532
Biological: PLACEBO
Biological: IL-15 adjuvant
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A PHASE Ib PARTIALLY RANDOMIZED PILOT STUDY INTENDED TO EVALUATE THE SAFETY AND IMMUNOLOGICAL EFFECTS OF HIV-1 DNA IMMUNIZATION (PENNVAX-B) WITH OR WITHOUT CO-ADMINISTRATION OF CONSTRUCTS CONTAINING DNA ENCODING FOR THE EXPRESSION OF EITHER IL-12 OR IL-15 IN HIV INFECTED INDIVIDUALS

Resource links provided by NLM:


Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:
  • Frequency of adverse events in each of the treatment arms [ Time Frame: Time of each vaccination, 2 weeks after vaccinations 3 and 4 and at the completion of the study. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Antigen specific cellular and humoral immune response. [ Time Frame: 2 weeks following the third and fourth vaccinations ] [ Designated as safety issue: No ]

Estimated Enrollment: 38
Study Start Date: September 2008
Study Completion Date: June 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PENNVAX-B alone
PENNVAX-B alone
Biological: PENNVAX-B
PENNVAX-B is a cocktail of three expression plasmids. The plasmids include the genes which encode a synthetic HIV-1 envelope protein (pEY2E1-B), Gag (gagCAM02), and Pol (pK2C1). Each plasmid is manufactured to a concentration of 4.0 mg/mL and is formulated with bupivacaine (0.25%) as a facilitating agent for DNA uptake. All plasmids (2.0 mg each gag, pol, env) are premixed by the manufacturer in the same vial.
Experimental: PENNVAX-B+IL12
PENNVAX-B+IL12
Biological: PENNVAX-B
PENNVAX-B is a cocktail of three expression plasmids. The plasmids include the genes which encode a synthetic HIV-1 envelope protein (pEY2E1-B), Gag (gagCAM02), and Pol (pK2C1). Each plasmid is manufactured to a concentration of 4.0 mg/mL and is formulated with bupivacaine (0.25%) as a facilitating agent for DNA uptake. All plasmids (2.0 mg each gag, pol, env) are premixed by the manufacturer in the same vial.
Biological: GENEVAX IL-12-4532
GENEVAX IL-12-4532 This molecular adjuvant plasmid contains nucleotide sequences necessary for expression of the human IL-12 protein. IL-12 DNA is formulated at a concentration of 2.0 mg/mL with bupivacaine (0.25%).
Experimental: PENNVAX-B+IL15
PENNVAX-B+IL15
Biological: PENNVAX-B
PENNVAX-B is a cocktail of three expression plasmids. The plasmids include the genes which encode a synthetic HIV-1 envelope protein (pEY2E1-B), Gag (gagCAM02), and Pol (pK2C1). Each plasmid is manufactured to a concentration of 4.0 mg/mL and is formulated with bupivacaine (0.25%) as a facilitating agent for DNA uptake. All plasmids (2.0 mg each gag, pol, env) are premixed by the manufacturer in the same vial.
Biological: IL-15 adjuvant
pIL15EAM is a plasmid that encodes human IL-15 and has been optimized to express 87 fold higher than native IL-15 DNA and 5.7 fold higher than an earlier generation optimized IL-15 DNA construct. This plasmid is formulated at a concentration of 4.0 mg/mL with bupivacaine (0.25%).
Placebo Comparator: PLACEBO
PLACEBO
Biological: PLACEBO
PLACEBO

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. HIV-1 infection documented by any licensed ELISA test kit and confirmed by Western blot, HIV-1 culture, HIV-1 antigen, or plasma HIV-1 RNA, at any time before study entry.
  2. Taking a stable HAART regimen for ≥3 months before the time of enrollment.
  3. CD4-positive lymphocyte count ≥400 cells/µl on two occasions within 60 days of enrollment, performed at any certified flow laboratory.
  4. HIV-1 < 75 copies/mL on two occasions within 60 days of enrollment, performed in a CLIA certified laboratory.
  5. Laboratory values obtained within 30 days prior to study entry:
  6. Hemoglobin > 9 g/dL (female subjects) and > 9.5 g/dL (male subjects)
  7. Absolute neutrophil count > 1000 cells/μL
  8. Platelet count > 75,000/μL
  9. ALT, AST and alkaline phosphatase ≥ 2.5 x upper limit of normal range
  10. Total bilirubin ≥ 2.5 x upper limit of the laboratory normal range
  11. Serum creatinine ≥ upper limit of normal (ULN).
  12. All women of reproductive potential (who have not reached menopause nor undergone hysterectomy, oophorectomy, or tubal ligation) must have a negative pregnancy test within 30 days of initiating study-specified medication(s) and at day 0 (enrollment).

    1. Women who are not of reproductive potential (have reached menopause or undergone hysterectomy, oophorectomy, or tubal ligation) or whose male partner has undergone successful vasectomy with resultant azoospermia or has azoospermia for any other reason, are eligible without requiring the use of contraception. Documentation of menopause, sterilization (hysterectomy, oophorectomy, tubal ligation, or vasectomy) and azoospermia by patient-reported history is acceptable.
    2. All subjects must not participate in a conception process (i.e. active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization), and if participating in sexual activity that could lead to pregnancy, the female study volunteer/male partner must use a form of contraception while receiving protocol-specified medication(s)/vaccinations and for one month after stopping the vaccinations.
  13. Karnofsky performance score ≥ 90 within 30 days prior to study entry.
  14. Men or women ≥18 years of age and less than 50.
  15. Ability and willingness of subject or legal guardian/representative to give written informed consent.

Exclusion Criteria:

  1. Any active or past AIDS-defining illness with the exception of minimal (less than 10 lesions) cutaneous Kaposi's sarcoma.
  2. Subjects with a history of a CD4+ T-cell count ≤200/µl are not eligible.
  3. Use of any known immunomodulatory therapy within 4 weeks prior to study entry including but not limited to drugs such as systemic corticosteroids, interferons, interleukins, thalidomide, granulocyte-macrophage colony-stimulating factor, IV gammaglobulin, or human growth hormone.
  4. Any malignancy requiring systemic or local toxic chemotherapy. Local radiation will be allowed.
  5. Pregnancy or breast-feeding.
  6. Uncontrolled diabetes mellitus (fasting blood glucose > 126 mg/dL or random blood glucose levels > 200 mg/dL on at least two occasions within 6 months prior to study entry).
  7. Major organ transplantation.
  8. Active alcohol or substance abuse or psychiatric illness, which in the opinion of the investigator will interfere with adherence to study requirements.
  9. Clinically significant neurological disorder occurring within 1 year prior to study entry that in the opinion of the principal investigator would affect the subject's study compliance or safety.
  10. Use of systemic corticosteroids for ≥ 4 weeks within 3 months prior to study entry.
  11. Presence of any chronic disease that in the opinion of the investigator might affect subject safety.
  12. History of previous vaccination with an HIV-1 vaccine.
  13. History or evidence of autoimmune disease, including, but not limited to thyroid autoimmune disease and idiopathic thrombocytopenic purpura.
  14. Allergies to bupivacaine or similar anesthetic.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00775424

Locations
United States, Pennsylvania
University of Pennsylvania. Clinical Trials Unit
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
University of Pennsylvania
Drexel University
Investigators
Principal Investigator: Pablo Tebas, MD University of Pennsylvania
  More Information

No publications provided

Responsible Party: Pablo Tebas, University of Pennsylvania
ClinicalTrials.gov Identifier: NCT00775424     History of Changes
Other Study ID Numbers: 807682
Study First Received: October 17, 2008
Last Updated: June 18, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Pennsylvania:
HIV infection
DNA vaccine
IL-12 adjuvant
IL-15 adjuvant

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 July 23, 2014