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

NCT01266616 | Completed Phase 1 DMC

• 2 other identifiers: A528110846
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 13

Brief Summary

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).

Conditions

HIV Infections

Keywords

Interleukin-12; Electroporation; HIV Therapeutic Vaccine

Outcome Measures

Primary Outcomes (2)

• 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

  From the first day of study treatment until 28 days after the last study vaccine administration

• 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)

  From Baseline to Week 14

Secondary Outcomes (5)

• 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?"

  From Week 0 to Week 36

• 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?"

  From Week 0 to Week 36

• Premature treatment discontinuation for reasons related to study treatment or related to any real or perceived effect of study vaccination or its administration

  From Week 0 to Week 36

• Rated pain (for participants administered vaccine/placebo by the EP device)

  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

• 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

  At Week 8, Week 14, and possibly other time points depending on the first set of data in an ICS assay

Study Arms (10)

Cohort 1: Vaccine alone IM/EP

EXPERIMENTAL

HIV MAG pDNA alone IM/EP

Biological: Profectus HIV MAG pDNA vaccine

Cohort 1: Placebo

PLACEBO COMPARATOR

Placebo given as an injection in each upper arm

Other: Placebo

Cohort 2: Vaccine plus IL-12 IM/EP

EXPERIMENTAL

HIV MAG pDNA plus 50 mcg of IL-12 pDNA IM/EP

Biological: Profectus HIV MAG pDNA vaccine; Biological: IL-12

Cohort 2: Placebo

PLACEBO COMPARATOR

Placebo given as an injection in each upper arm

Other: Placebo

Cohort 3: Vaccine plus IL-12 IM/EP

EXPERIMENTAL

HIV MAG pDNA plus 250 mcg of IL-12 pDNA IM/EP

Biological: Profectus HIV MAG pDNA vaccine; Biological: IL-12

Cohort 3: Placebo

PLACEBO COMPARATOR

Placebo given as an injection in each upper arm

Other: Placebo

Cohort 4: Vaccine plus IL-12 IM/EP

EXPERIMENTAL

HIV MAG pDNA plus 1,000 mcg of IL-12 pDNA IM/EP

Biological: Profectus HIV MAG pDNA vaccine; Biological: IL-12

Cohort 4: Placebo

PLACEBO COMPARATOR

Placebo given as an injection in each upper arm

Other: Placebo

Cohort 5: Vaccine plus IL-12 IM

EXPERIMENTAL

HIV MAG pDNA plus 1,000 mcg (or highest dose reached) IL-12 pDNA IM

Biological: Profectus HIV MAG pDNA vaccine; Biological: IL-12

Cohort 5: Placebo

PLACEBO COMPARATOR

Placebo given as an injection in each upper arm

Other: Placebo

Interventions

Profectus HIV MAG pDNA vaccine BIOLOGICAL

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

Cohort 1: Vaccine alone IM/EP; Cohort 2: Vaccine plus IL-12 IM/EP; Cohort 3: Vaccine plus IL-12 IM/EP; Cohort 4: Vaccine plus IL-12 IM/EP; Cohort 5: Vaccine plus IL-12 IM

IL-12 BIOLOGICAL

Administered at Weeks 0, 4, and 12

Cohort 2: Vaccine plus IL-12 IM/EP; Cohort 3: Vaccine plus IL-12 IM/EP; Cohort 4: Vaccine plus IL-12 IM/EP; Cohort 5: Vaccine plus IL-12 IM

Placebo OTHER

Saline injections at Weeks 0, 4, and 12

Cohort 1: Placebo; Cohort 2: Placebo; Cohort 3: Placebo; Cohort 4: Placebo; Cohort 5: Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (13)

UCLA CARE Center CRS

Los Angeles, California, 90035, United States

Location

Stanford AIDS Clinical Trials Unit CRS

Palo Alto, California, 94304-5350, United States

Location

Ucsf Hiv/Aids Crs

San Francisco, California, 94110, United States

Location

University of Colorado Hospital CRS

Aurora, Colorado, 80045, United States

Location

Massachusetts General Hospital Clinical Research Site (MGH CRS) CRS

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital Therapeutics Clinical Research Site (BWH TCRS) CRS

Boston, Massachusetts, 02115, United States

Location

Washington University Therapeutics (WT) CRS

St Louis, Missouri, 63110, United States

Location

Trillium Health ACTG CRS

Rochester, New York, 14607, United States

Location

Univ. of Rochester ACTG CRS

Rochester, New York, 14642, United States

Location

Cincinnati CRS

Cincinnati, Ohio, 45219, United States

Location

Penn Therapeutics Crs

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh CRS

Pittsburgh, Pennsylvania, 15213-2582, United States

Location

Houston AIDS Research Team CRS

Houston, Texas, 77030, United States

Location

Related Publications (4)

• Finzi D, Blankson J, Siliciano JD, Margolick JB, Chadwick K, Pierson T, Smith K, Lisziewicz J, Lori F, Flexner C, Quinn TC, Chaisson RE, Rosenberg E, Walker B, Gange S, Gallant J, Siliciano RF. Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy. Nat Med. 1999 May;5(5):512-7. doi: 10.1038/8394.

  PMID: 10229227 BACKGROUND

• Koup RA, Safrit JT, Cao Y, Andrews CA, McLeod G, Borkowsky W, Farthing C, Ho DD. Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome. J Virol. 1994 Jul;68(7):4650-5. doi: 10.1128/JVI.68.7.4650-4655.1994.

  PMID: 8207839 BACKGROUND

• Luxembourg A, Evans CF, Hannaman D. Electroporation-based DNA immunisation: translation to the clinic. Expert Opin Biol Ther. 2007 Nov;7(11):1647-64. doi: 10.1517/14712598.7.11.1647.

  PMID: 17961089 BACKGROUND

• Jacobson JM, Zheng L, Wilson CC, Tebas P, Matining RM, Egan MA, Eldridge J, Landay AL, Clifford DB, Luetkemeyer AF, Tiu J, Martinez AL, Janik J, Spitz TA, Hural J, McElrath J, Frahm N; ACTG A5281 Protocol Team. The Safety and Immunogenicity of an Interleukin-12-Enhanced Multiantigen DNA Vaccine Delivered by Electroporation for the Treatment of HIV-1 Infection. J Acquir Immune Defic Syndr. 2016 Feb 1;71(2):163-71. doi: 10.1097/QAI.0000000000000830.

  PMID: 26761518 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Interleukin-12

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

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Jeffrey Jacobson, MD

  Division of Infectious Diseases and HIV Medicine, Drexel University College of Medicine

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2010
• First Posted: December 24, 2010
• Study Start: March 1, 2011
• Primary Completion: October 1, 2012
• Study Completion: April 1, 2013
• Last Updated: November 1, 2021

Record last verified: 2021-10

Locations

US (13)