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Therapeutic Intensification Plus Immunomodulation in HIV-infected Patients (ERAMUNE-01)

12 de junio de 2013 actualizado por: Objectif Recherche Vaccins SIDA

International, Multicenter, Randomized, Non-comparative Controlled Study of Therapeutic Intensification Plus Immunomodulation in HIV-infected Patients With Long-term Viral Suppression

Viral eradication in selected HIV-infected patients is possible with intensive antiretroviral therapy plus immunomodulation

Descripción general del estudio

Estado

Terminado

Condiciones

Descripción detallada

The overall strategy of the ERAMUNE 01 Trial is to treat selected patients with an optimal synergistic antiretroviral regimen plus one or more immunomodulating agents. Among immunomodulating treatments the candidates include therapies from two functional classes: 1) agents that target actively replicating cells and 2) agents activating latently infected cells31.

The novelty of this approach is three-fold: first, the use of highly potent antiretroviral therapy combining drugs with different HIV enzymes targets or receptors and different penetrations in cells, with the aim to suppress virus to truly undetectable levels as measured by the most sophisticated viral quantification techniques; secondly, the addition of an immunomodulatory therapy that specifically targets viral reservoirs to this intensification strategy; and lastly, the rigorous selection of patients having already a low HIV reservoir as measured by peripheral blood HIV DNA content. To our knowledge, this type of strategy has not been implemented. We believe this strategy is feasible.

Tipo de estudio

Intervencionista

Inscripción (Actual)

29

Fase

  • Fase 2

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

      • Badalona, España, 08916
        • Fundacio Irsicaixa
      • Barcelona, España, 08036
        • University Hospital Clinic of Barcelona
      • Paris, Francia, 75013
        • Groupe Hospitalier Pitie-Salpetriere
      • Milan, Italia, 20127
        • San Raffaele Scientific Institute
      • London, Reino Unido, NW3 2QG
        • Royal Free Hospital

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

18 años a 70 años (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

Inclusion Criteria:

  • HIV-1 infection, documented by any licensed ELISA test kit and confirmed by Western Blot at any time prior to study entry. HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA is acceptable as an alternative confirmatory test
  • 18 ≤ Age ≤ 70 years
  • At least 3 years of suppressive ART without any interruption (less than one month cumulative),
  • ART treatment unchanged in the 3 months prior to screening
  • One HIV plasma viral load (RNA) documented at least 3 years prior to entry, and at least 2 HIV plasma viral loads (RNA) documented per year thereafter
  • HIV plasma viral load (RNA) ≤ 500 copies/ml at least 3 years prior to entry and HIV plasma viral load ≤ 500 copies/ml for ≥ 90% of the measures thereafter
  • HIV plasma viral load (RNA) below the limit of detection for all values within the past year. Note: the assay used must have a lower limit of detection of 75 copies/ml or less
  • CD4+ count ≥ 350 cells/mm3 within 60 days of entry
  • 10 ≤ Proviral DNA ≤ 1000 copies/106 PBMCs within 60 days of entry
  • Documented laboratory values: Haemoglobin ≥ 10 g/dl, Platelets ≥ 100,000 per microliter, Hepatic transaminases ≤ 2.5 x ULN, Creatinine clearance ≥ 50 ml/min by the Cockcroft-Gault equation
  • All subjects must agree not to participate in the conception process (e.g. 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 subject/partner must use at least two reliable forms of contraceptives (condoms, with or without spermicidal agent, a diaphragm or cervical cap with spermicide, an IUD, or hormone-based contraception), while receiving study treatment and for 6 weeks after stopping study treatment
  • Ability and willingness to provide informed consent.

Exclusion Criteria:

  • Sexually active men and women who will not practice at least one form of barrier birth control (male partner using condoms, female partner using condoms, other barrier contraception, etc)
  • Pregnancy as documented by a urine pregnancy test, or lactating women
  • Hepatitis B antigen (HBsAg) positive
  • Hepatitis C virus (HCV-Ab) positive or HCV RNA detectable
  • Previous use of an integrase inhibitor (ie raltegravir) or a CCR5 inhibitor (ie maraviroc, vicriviroc). Use of raltegravir for non-treatment failure indications such as intensification and toxicity switches is allowed, provided that 1) virologic suppression was maintained before, during and after raltegravir treatment and 2) the patient has not received raltegravir treatment in the 6 months prior to study entry.
  • Previous immunologic therapeutic intervention (e.g. IL-2, IL-7) within the past year
  • Participation in another clinical drug or device trial where the last dose of drug was within the past 30 days or an investigational medical device is currently implanted
  • Diagnosis of cancer within the last 5 years (except basal cell cutaneous cancers and cutaneous KS not requiring systemic therapy)
  • Co-morbid condition with an expected survival less than 12 months
  • History of hypersensitivity to vaccination
  • History of autoimmune disease, such as systemic lupus erythematosis (SLE) or Hashimoto's thyroiditis
  • Active drug or alcohol use or dependence that, in the opinion of the center investigator, would interfere with adherence to study requirements.

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: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: ARM A : ART intensification alone
Raltegravir PO 400 mg BID Maraviroc PO 150, 300 or 600 mg BID depending on the concomitant ART regimen
Current ART regimen plus raltegravir and maraviroc Raltegravir : 400 mg PO BID for 56 weeks Maraviroc : 150, 300 or 600 mg PO BID depending on concomitant ART treatment, for 56 weeks
Experimental: ARM B : ART intensification + Immunomodulation
Raltegravir PO 400 mg BID during 56 weeks Maraviroc PO 150, 300 or 600 mg BID depending on the concomitant ART regimen during 56 weeks 3 weekly injections of r-hIL-7 (CYT107) at a 20 micrograms/kg dose starting at Week 8
Current ART regimen plus raltegravir and maraviroc Raltegravir : 400 mg PO BID for 56 weeks Maraviroc : 150, 300 or 600 mg PO BID depending on concomitant ART treatment, for 56 weeks
Starting at Week 8, 1 cycle of 3 injections (1 per week) of recombinant human Interleukin-7 (r-hIL-7 / CYT107) at a 20 µg/kg dose.

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Periodo de tiempo
Decrease from baseline in HIV proviral DNA in the PBMCs at week 56 of at least 0.5 log, as expressed as numbers of HIV DNA copies per million PBMCs
Periodo de tiempo: End of study
End of study

Medidas de resultado secundarias

Medida de resultado
Periodo de tiempo
Percentage of patients with undetectable HIV DNA (< 1 copy/million PBMCs) after 56 weeks
Periodo de tiempo: End of study
End of study
Change from baseline in HIV proviral DNA in any of the sub-compartments explored (gut lymphoid tissue), as expressed as numbers of HIV DNA copies per million mononuclear cells
Periodo de tiempo: From Day 0 to Week 56
From Day 0 to Week 56
Change from baseline in HIV proviral DNA in the CD4 T cell subsets, as expressed as numbers of HIV DNA copies per million CD4 T cells
Periodo de tiempo: From Day 0 to Week 56
From Day 0 to Week 56
Changes from baseline in HIV plasma viral load (number of copies of HIV RNA per millilitre), measured by quantitative ultrasensitive PCR
Periodo de tiempo: From Day 0 to Week 56
From Day 0 to Week 56
Proportion of patients without inducible HIV RNA, DNA and/or p24
Periodo de tiempo: End of study
End of study
Changes from baseline in CD4 lymphocyte count
Periodo de tiempo: From Day 0 to Week 56
From Day 0 to Week 56
Changes in the activation and differentiation markers of the CD4 and CD8 peripheral blood T cells
Periodo de tiempo: End of study
End of study
Development of a mathematical model exploring the dynamics of the HIV-DNA decay
Periodo de tiempo: From Day 0 to Week 56
From Day 0 to Week 56
Development of a mathematical model exploring the dynamics of T cells activation (CD38)
Periodo de tiempo: From Day 0 to Week 56
From Day 0 to Week 56
Genetic determinants influencing HIV-1-specific immune response and HIV control
Periodo de tiempo: End of study
End of study
Antiretroviral drugs pharmacokinetics in the blood and rectal mucosa
Periodo de tiempo: From Day 0 to Week 56
From Day 0 to Week 56
Safety and tolerability of the intensified treatment regimen and immunomodulatory therapy
Periodo de tiempo: From Day 0 to Week 56
From Day 0 to Week 56

Colaboradores e Investigadores

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

Investigadores

  • Investigador principal: Christine Katlama, MD, Groupe Hospitalier Pitie-Salpetriere
  • Director de estudio: François LECARDONNEL, MSc, ORVACS
  • Silla de estudio: Steven DEEKS, MD, University of California, San Francisco

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.

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 septiembre de 2010

Finalización primaria (Actual)

1 de julio de 2012

Finalización del estudio (Actual)

1 de febrero de 2013

Fechas de registro del estudio

Enviado por primera vez

23 de noviembre de 2009

Primero enviado que cumplió con los criterios de control de calidad

24 de noviembre de 2009

Publicado por primera vez (Estimar)

25 de noviembre de 2009

Actualizaciones de registros de estudio

Última actualización publicada (Estimar)

13 de junio de 2013

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

12 de junio de 2013

Última verificación

1 de junio de 2013

Más información

Términos relacionados con este estudio

Otros números de identificación del estudio

  • ORVACS 010

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. .

Ensayos clínicos sobre Infección por VIH-1

Ensayos clínicos sobre ART Intensification

3
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