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Ensayos clínicos

Ensayos clínicos

Safety and Immune Response to Vicriviroc in Combination Regimens in HIV-Infected Antiretroviral Treatment Experienced Children and Adolescents

Patrocinador(es) del estudio: National Institute of Allergy and Infectious Diseases (NIAID)
Números de identificación: NCT00766597, IMPAACT P1071
  • Concluido

Propósito del estudio

Complications with current HIV antiretroviral therapy have left many children and adolescents with limited therapeutic options due to drug resistance. The purpose of this study is to test the effectiveness and safety of Vivriviroc (VCV), an HIV entry inhibitor and CCR5 co-receptor antagonist.

Afección:Fase:
Infecciones por el VIH
Fase 1/Fase 2

Detalles del estudio

Highly active antiretroviral therapy (HAART)that includes a protease inhibitor (PI) or a

non-nucleoside reverse transcriptase inhibitor (NNRTI) has become the standard treatment of

HIV-infected adults and children. When effective, HAART decreases the viral population,

increases the body's immune responses, and leads to decreased disease progression and

increased survival. However, several factors including poor adherence, drug toxicities, and

drug resistance complicate HIV management and allow for children and adolescents to develop

resistance to multiple drug classes, leaving them with very limited therapeutic options.

Fortunately, drugs with new mechanisms of action, such as HIV entry inhibitors, demonstrate

activity even in people with resistance to the currently available reverse transcriptase and

protease inhibitors.



The purpose of this study is to test the effectiveness and safety of Vivriviroc (VCV), an

HIV entry inhibitor. Vivriviroc targets the CCR5 chemokine receptor, which HIV uses to bind

and enter CD4+ cells.



This study is a two-stage, age-stratified, non-comparative study to explore the safety,

tolerability, pharmacokinetic profile and antiviral activity of the investigational CCR5

inhibitor vicriviroc in HIV-infected treatment experienced children and adolescents.



In Step I participants will be screened for the co-receptor CCR5 to assess whether they can

enter Step II. Only participants with CCR5-tropic virus are eligible for Step II. Those

participants who continue to Step II will be assigned to one of four age-stratifies cohorts

which will receive varying forms, either liquid or tablet, of vicriviroc:



Cohort I: 12 years to less than 19 years of age, to receive tablet formulation of VCV



Cohort II: 6 years to less than 12 years of age, to receive tablet formulation of VCV



Cohort III: 6 years to less than 12 years of age, to receive liquid formulation of VCV



Cohort IV: 2 years to less than 6 years of age, to receive liquid formulation of VCV



Dose strengths of 20 mg and 30 mg will be used, or in liquid formulation at a concentration

of 1mg/mL.



Step II is composed of Stage I and Stage II. Stage I is a dose ranging study designed to

explore how the body responds to different doses of vicriviroc, including safety factors

associated with dosage. After optimal dosage information and safety measures have been

assessed for the different cohorts in Stage I, Stage II will open. Stage II will evaluate

the long term safety, tolerability and effectiveness of vicriviroc.



The study, including Steps I and II will last for approximately 48 weeks. Follow-up for all

subjects exposed to vicriviroc will last for 5 years after initial exposure. Visits will be

every 3 months for subjects on study provided vicriviroc and every 6 months for subjects

who discontinue vicriviroc.Highly active antiretroviral therapy (HAART)that includes a protease inhibitor (PI) or a

non-nucleoside reverse transcriptase inhibitor (NNRTI) has become the standard treatment of

HIV-infected adults and children. When effective, HAART decreases the viral population,

increases the body's immune responses, and leads to decreased disease progression and

increased survival. However, several factors including poor adherence, drug toxicities, and

drug resistance complicate HIV management and allow for children and adolescents to develop

resistance to multiple drug classes, leaving them with very limited therapeutic options.

Fortunately, drugs with new mechanisms of action, such as HIV entry inhibitors, demonstrate

activity even in people with resistance to the currently available reverse transcriptase and

protease inhibitors.



The purpose of this study is to test the effectiveness and safety of Vivriviroc (VCV), an

HIV entry inhibitor. Vivriviroc targets the CCR5 chemokine receptor, which HIV uses to bind

and enter CD4+ cells.



This study is a two-stage, age-stratified, non-comparative study to explore the safety,

tolerability, pharmacokinetic profile and antiviral activity of the investigational CCR5

inhibitor vicriviroc in HIV-infected treatment experienced children and adolescents.



In Step I participants will be screened for the co-receptor CCR5 to assess whether they can

enter Step II. Only participants with CCR5-tropic virus are eligible for Step II. Those

participants who continue to Step II will be assigned to one of four age-stratifies cohorts

which will receive varying forms, either liquid or tablet, of vicriviroc:



Cohort I: 12 years to less than 19 years of age, to receive tablet formulation of VCV



Cohort II: 6 years to less than 12 years of age, to receive tablet formulation of VCV



Cohort III: 6 years to less than 12 years of age, to receive liquid formulation of VCV



Cohort IV: 2 years to less than 6 years of age, to receive liquid formulation of VCV



Dose strengths of 20 mg and 30 mg will be used, or in liquid formulation at a concentration

of 1mg/mL.



Step II is composed of Stage I and Stage II. Stage I is a dose ranging study designed to

explore how the body responds to different doses of vicriviroc, including safety factors

associated with dosage. After optimal dosage information and safety measures have been

assessed for the different cohorts in Stage I, Stage II will open. Stage II will evaluate

the long term safety, tolerability and effectiveness of vicriviroc.



The study, including Steps I and II will last for approximately 48 weeks. Follow-up for all

subjects exposed to vicriviroc will last for 5 years after initial exposure. Visits will be

every 3 months for subjects on study provided vicriviroc and every 6 months for subjects

who discontinue vicriviroc.

Criterios de inclusión

    :
    • Confirmed HIV infection
    • Treatment experienced subjects: Children or adolescents on an unchanged therapeutic
    regimen for at least 12 weeks and experiencing virologic failure OR participants on no treatment for 4 weeks or more but with history of virologic failure on a prior therapeutic regimen.
    • Likely to have virus that is sensitive to at least one ritonavir boosted protease
    inhibitor
    • HIV viral load greater than or equal to 1,000 copies/ml within 90 days prior to Step
    I entry
    • Able to swallow study medication, in tablets or liquid form specific to age-assigned
    cohort
    • Parent, legal guardian or participant able and willing to provide signed informed
    consent and to have the participant followed at the clinic site
    • Willing to use effective methods of contraception
    for Step II (In addition to the inclusion criteria for Step I):
    • Participant's plasma HIV tested at Step I must be R5 tropic
    • Genotypic sensitivity enabling the participant to take optimized background therapy
    (OBT) consisting of at least a ritonavir-based protease inhibitor. More information on this criterion can be found in the study protocol.

Criterios de exclusión

    :
    • Presence of any currently active AIDS defining illness or history of malignancy
    • History of a seizure disorder that requires current anti-seizure medication for
    control or at risk for seizures. Those with a history of febrile seizures alone are not excluded.
    • Certain abnormal laboratory values. More information on this criterion can be found
    in the protocol.
    • Any vaccinations 14 days prior to Step I, or scheduled to occur within 14 days prior
    to entry into Step II, and the week 24 and 48 visits in Step II
    • Allergy or sensitivity to study drug or its ingredients
    • Taking any Step II disallowed medications (see protocol) and unable or unwilling to
    discontinue them at least one week prior to entering Step II
    • Use of NNRTIs other than etravirine 21 days prior to Step II entry
    • Pregnancy or breastfeeding. Infants who are receiving breastmilk are allowed to
    enroll.

Centros de estudio/contactos

California

    UCSD Mother-Child-Adolescent Program CRS, San Diego, California, United States

District of Columbia

    Howard Univ. Washington DC NICHD CRS, Washington, District of Columbia, 20060, United States

    Children's National Med. Ctr. Washington DC NICHD CRS, Washington, District of Columbia, 20010, United States

Illinois

    Chicago Children's CRS, Chicago, Illinois, 60614, United States

New York

    Jacobi Med. Ctr. Bronx NICHD CRS, Bronx, New York, 10461, United States

    Bronx-Lebanon Hosp. IMPAACT CRS, Bronx, New York, 10461, United States

    Metropolitan Hosp. NICHD CRS, New York, New York, 10029, United States

Tennessee

    St. Jude/UTHSC CRS, Memphis, Tennessee, 38105, United States

    Univ. of Puerto Rico Ped. HIV/AIDS Research Program CRS, San Juan, Tennessee, 00935, Puerto Rico

Actualizado: 30 de agosto del 2010

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