Esta página foi traduzida automaticamente e a precisão da tradução não é garantida. Por favor, consulte o versão em inglês para um texto fonte.

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 outubro de 2021 atualizado 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).

Visão geral do estudo

Status

Concluído

Condições

Intervenção / Tratamento

Descrição detalhada

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 estudo

Intervencional

Inscrição (Real)

62

Estágio

  • Fase 1

Contactos e Locais

Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.

Locais de estudo

  • 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

Critérios de participação

Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.

Critérios de elegibilidade

Idades elegíveis para estudo

14 anos a 51 anos (Adulto)

Aceita Voluntários Saudáveis

Não

Gêneros Elegíveis para o Estudo

Tudo

Descrição

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)

Plano de estudo

Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.

Como o estudo é projetado?

Detalhes do projeto

  • Finalidade Principal: Tratamento
  • Alocação: Randomizado
  • Modelo Intervencional: Atribuição Paralela
  • Mascaramento: Dobro

Armas e Intervenções

Grupo de Participantes / Braço
Intervenção / Tratamento
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 Placebo: Cohort 1: Placebo
Placebo given as an injection in each upper arm
Outro: 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 Placebo: Cohort 2: Placebo
Placebo given as an injection in each upper arm
Outro: 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 Placebo: Cohort 3: Placebo
Placebo given as an injection in each upper arm
Outro: 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 Placebo: Cohort 4: Placebo
Placebo given as an injection in each upper arm
Outro: 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 Placebo: Cohort 5: Placebo
Placebo given as an injection in each upper arm
Outro: Placebo
Saline injections at Weeks 0, 4, and 12

O que o estudo está medindo?

Medidas de resultados primários

Medida de resultado
Prazo
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
Prazo: 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)
Prazo: From Baseline to Week 14
From Baseline to Week 14

Medidas de resultados secundários

Medida de resultado
Prazo
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?"
Prazo: 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?"
Prazo: 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
Prazo: From Week 0 to Week 36
From Week 0 to Week 36
Rated pain (for participants administered vaccine/placebo by the EP device)
Prazo: 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
Prazo: 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

É aqui que você encontrará pessoas e organizações envolvidas com este estudo.

Patrocinador

National Institute of Allergy and Infectious Diseases (NIAID)

Investigadores

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

Publicações e links úteis

A pessoa responsável por inserir informações sobre o estudo fornece voluntariamente essas publicações. Estes podem ser sobre qualquer coisa relacionada ao estudo.

Publicações Gerais

Datas de registro do estudo

Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados ​​pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.

Datas Principais do Estudo

Início do estudo

1 de março de 2011

Conclusão Primária (Real)

1 de outubro de 2012

Conclusão do estudo (Real)

1 de abril de 2013

Datas de inscrição no estudo

Enviado pela primeira vez

23 de dezembro de 2010

Enviado pela primeira vez que atendeu aos critérios de CQ

23 de dezembro de 2010

Primeira postagem (Estimativa)

24 de dezembro de 2010

Atualizações de registro de estudo

Última Atualização Postada (Real)

1 de novembro de 2021

Última atualização enviada que atendeu aos critérios de controle de qualidade

28 de outubro de 2021

Última verificação

1 de outubro de 2021

Mais Informações

Termos relacionados a este estudo

Palavras-chave

Termos MeSH relevantes adicionais

Outros números de identificação do estudo

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

Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .

Se inscrever