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

NCT00775424 | Completed Phase 1 DMC

• 1 other identifier: 807682
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

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. 1.To determine the safety of HIV-1 DNA constructs (PENNVAX-B).
2. 2.To determine the safety and optimal doses of the IL-12 and the IL-15 adjuvant constructs when given with PENNVAX-B.
3. 3.To compare the various vaccine groups for their immunological responses to several HIV-1 antigens, utilizing the ELISPOT assay.
4. 4.To analyze antibody responses to the vaccine antigens over time.
5. 5.To measure CD8 cell proliferative responses to vaccine antigens over time.

Conditions

HIV Infection

Keywords

HIV infection; DNA vaccine; IL-12 adjuvant; IL-15 adjuvant

Outcome Measures

Primary Outcomes (1)

• Frequency of adverse events in each of the treatment arms

  Time of each vaccination, 2 weeks after vaccinations 3 and 4 and at the completion of the study.

Secondary Outcomes (1)

• Antigen specific cellular and humoral immune response.

  2 weeks following the third and fourth vaccinations

Study Arms (4)

PENNVAX-B alone

EXPERIMENTAL

PENNVAX-B alone

Biological: PENNVAX-B

PENNVAX-B+IL12

EXPERIMENTAL

PENNVAX-B+IL12

Biological: PENNVAX-B; Biological: GENEVAX IL-12-4532

PENNVAX-B+IL15

EXPERIMENTAL

PENNVAX-B+IL15

Biological: PENNVAX-B; Biological: IL-15 adjuvant

PLACEBO

PLACEBO COMPARATOR

PLACEBO

Biological: PLACEBO

Interventions

PENNVAX-B BIOLOGICAL

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.

PENNVAX-B alone; PENNVAX-B+IL12; PENNVAX-B+IL15

GENEVAX IL-12-4532 BIOLOGICAL

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%).

PENNVAX-B+IL12

PLACEBO BIOLOGICAL

PLACEBO

PLACEBO

IL-15 adjuvant BIOLOGICAL

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%).

PENNVAX-B+IL15

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• Taking a stable HAART regimen for ≥3 months before the time of enrollment.
• CD4-positive lymphocyte count ≥400 cells/µl on two occasions within 60 days of enrollment, performed at any certified flow laboratory.
• HIV-1 \< 75 copies/mL on two occasions within 60 days of enrollment, performed in a CLIA certified laboratory.
• Laboratory values obtained within 30 days prior to study entry:
• Hemoglobin \> 9 g/dL (female subjects) and \> 9.5 g/dL (male subjects)
• Absolute neutrophil count \> 1000 cells/μL
• Platelet count \> 75,000/μL
• ALT, AST and alkaline phosphatase ≥ 2.5 x upper limit of normal range
• Total bilirubin ≥ 2.5 x upper limit of the laboratory normal range
• Serum creatinine ≥ upper limit of normal (ULN).
• 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).
• 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.
• 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.
• Karnofsky performance score ≥ 90 within 30 days prior to study entry.

You may not qualify if:

• Any active or past AIDS-defining illness with the exception of minimal (less than 10 lesions) cutaneous Kaposi's sarcoma.
• Subjects with a history of a CD4+ T-cell count ≤200/µl are not eligible.
• 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.
• Any malignancy requiring systemic or local toxic chemotherapy. Local radiation will be allowed.
• Pregnancy or breast-feeding.
• 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).
• Major organ transplantation.
• Active alcohol or substance abuse or psychiatric illness, which in the opinion of the investigator will interfere with adherence to study requirements.
• 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.
• Use of systemic corticosteroids for ≥ 4 weeks within 3 months prior to study entry.
• Presence of any chronic disease that in the opinion of the investigator might affect subject safety.
• History of previous vaccination with an HIV-1 vaccine.
• History or evidence of autoimmune disease, including, but not limited to thyroid autoimmune disease and idiopathic thrombocytopenic purpura.
• Allergies to bupivacaine or similar anesthetic.

Sponsors & Collaborators

• University of Pennsylvania: lead
• Drexel University: collaborator

Study Sites (1)

University of Pennsylvania. Clinical Trials Unit

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Pablo Tebas, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 17, 2008
• First Posted: October 20, 2008
• Study Start: September 1, 2008
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2010
• Last Updated: August 25, 2016

Record last verified: 2016-08

Locations

US (1)