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

28 de octubre de 2021 actualizado por: National Institute of Allergy and Infectious Diseases (NIAID)

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

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).

Descripción general del estudio

Estado

Terminado

Condiciones

Intervención / Tratamiento

Descripción detallada

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.

Tipo de estudio

Intervencionista

Inscripción (Actual)

62

Fase

  • Fase 1

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

  • Estados Unidos
    • California
      • Los Angeles, California, Estados Unidos, 90035
        • UCLA CARE Center CRS
      • Palo Alto, California, Estados Unidos, 94304-5350
        • Stanford AIDS Clinical Trials Unit CRS
      • San Francisco, California, Estados Unidos, 94110
        • Ucsf Hiv/Aids Crs
    • Colorado
      • Aurora, Colorado, Estados Unidos, 80045
        • University of Colorado Hospital CRS
    • Massachusetts
      • Boston, Massachusetts, Estados Unidos, 02114
        • Massachusetts General Hospital Clinical Research Site (MGH CRS) CRS
      • Boston, Massachusetts, Estados Unidos, 02115
        • Brigham and Women's Hospital Therapeutics Clinical Research Site (BWH TCRS) CRS
    • Missouri
      • Saint Louis, Missouri, Estados Unidos, 63110
        • Washington University Therapeutics (WT) CRS
    • New York
      • Rochester, New York, Estados Unidos, 14642
        • Univ. of Rochester ACTG CRS
      • Rochester, New York, Estados Unidos, 14607
        • Trillium Health ACTG CRS
    • Ohio
      • Cincinnati, Ohio, Estados Unidos, 45219
        • Cincinnati CRS
    • Pennsylvania
      • Philadelphia, Pennsylvania, Estados Unidos, 19104
        • Penn Therapeutics CRS
      • Pittsburgh, Pennsylvania, Estados Unidos, 15213-2582
        • University of Pittsburgh CRS
    • Texas
      • Houston, Texas, Estados Unidos, 77030
        • Houston AIDS Research Team CRS

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

14 años a 51 años (Adulto)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

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)

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: Aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Doble

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: Cohort 1: Vaccine alone IM/EP
HIV MAG pDNA alone IM/EP
Biológico: 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
Comparador de placebos: Cohort 1: Placebo
Placebo given as an injection in each upper arm
Otro: 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
Biológico: 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
Biológico: IL-12
Administered at Weeks 0, 4, and 12
Comparador de placebos: Cohort 2: Placebo
Placebo given as an injection in each upper arm
Otro: 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
Biológico: 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
Biológico: IL-12
Administered at Weeks 0, 4, and 12
Comparador de placebos: Cohort 3: Placebo
Placebo given as an injection in each upper arm
Otro: 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
Biológico: 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
Biológico: IL-12
Administered at Weeks 0, 4, and 12
Comparador de placebos: Cohort 4: Placebo
Placebo given as an injection in each upper arm
Otro: 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
Biológico: 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
Biológico: IL-12
Administered at Weeks 0, 4, and 12
Comparador de placebos: Cohort 5: Placebo
Placebo given as an injection in each upper arm
Otro: Placebo
Saline injections at Weeks 0, 4, and 12

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Periodo de tiempo
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
Periodo de tiempo: From the first day of study treatment until 28 days after the last study vaccine administration
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)
Periodo de tiempo: From Baseline to Week 14
From Baseline to Week 14

Medidas de resultado secundarias

Medida de resultado
Periodo de tiempo
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?"
Periodo de tiempo: From Week 0 to Week 36
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?"
Periodo de tiempo: From Week 0 to Week 36
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
Periodo de tiempo: From Week 0 to Week 36
From Week 0 to Week 36
Rated pain (for participants administered vaccine/placebo by the EP device)
Periodo de tiempo: 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
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
Periodo de tiempo: At Week 8, Week 14, and possibly other time points depending on the first set of data in an ICS assay
At Week 8, Week 14, and possibly other time points depending on the first set of data in an ICS assay

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

National Institute of Allergy and Infectious Diseases (NIAID)

Investigadores

  • Silla de estudio: Jeffrey Jacobson, MD, Division of Infectious Diseases and HIV Medicine, Drexel University College of Medicine

Publicaciones y enlaces útiles

La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.

Publicaciones Generales

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio

1 de marzo de 2011

Finalización primaria (Actual)

1 de octubre de 2012

Finalización del estudio (Actual)

1 de abril de 2013

Fechas de registro del estudio

Enviado por primera vez

23 de diciembre de 2010

Primero enviado que cumplió con los criterios de control de calidad

23 de diciembre de 2010

Publicado por primera vez (Estimar)

24 de diciembre de 2010

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

1 de noviembre de 2021

Última actualización enviada que cumplió con los criterios de control de calidad

28 de octubre de 2021

Última verificación

1 de octubre de 2021

Más información

Términos relacionados con este estudio

Palabras clave

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • A5281
  • 10846 (Identificador de registro: DAIDS ES Registry Number)

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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