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An Open Label Pharmacokinetic, Safety And Efficacy Study Of Maraviroc In Combination With Background Therapy For The Treatment Of HIV-1 Infected, CCR5 -Tropic Children

17 de abril de 2020 actualizado por: ViiV Healthcare

AN OPEN-LABEL, MULTICENTER, MULTIPLE-DOSE PHARMACOKINETIC, SAFETY AND EFFICACY TRIAL OF MARAVIROC IN COMBINATION WITH OPTIMIZED BACKGROUND THERAPY FOR THE TREATMENT OF ANTIRETROVIRAL-EXPERIENCED CCR5-TROPIC HIV-1 INFECTED CHILDREN 2 - <18 YEARS OF AGE

The primary purpose of this study is to determine the pharmacokinetic properties (what the body does to maraviroc) and to determine a suitable dosing schedule of maraviroc in HIV-1 infected children and adolescents. This study will also determine whether maraviroc is safe to use in children and adolescents.

Descripción general del estudio

Estado

Activo, no reclutando

Condiciones

Intervención / Tratamiento

Tipo de estudio

Intervencionista

Inscripción (Actual)

103

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

  • Brasil
      • São Paulo, Brasil, 01416-000
        • Condomínio Edifício Parque Paulista
    • SP
      • São Paulo, SP, Brasil, 01246-900
        • Instituto de Infectologia Emilio Ribas
  • España
      • Esplugues De Llobregat, Barcelona, España, 08950
        • Hospital Sant Joan de Déu
      • Madrid, España, 28041
        • Hospital Universitario 12 de Octubre
  • Estados Unidos
    • California
      • Los Angeles, California, Estados Unidos, 90027
        • Children's Hospital Los Angeles
      • Orange, California, Estados Unidos, 92868
        • Children's Hospital of Orange County
    • Delaware
      • Wilmington, Delaware, Estados Unidos, 19803
        • Alfred I. DuPont Hospital for Children
    • District of Columbia
      • Washington, District of Columbia, Estados Unidos, 20010
        • Children's National Medical Center
    • Florida
      • Jacksonville, Florida, Estados Unidos, 32209
        • Rainbow Center at University of Florida Health
      • Miami, Florida, Estados Unidos, 33136
        • University of Miami Miller School of Medicine
      • Tampa, Florida, Estados Unidos, 33612
        • University of South Florida
    • Georgia
      • Atlanta, Georgia, Estados Unidos, 30322
        • Children's Healthcare of Atlanta
      • Atlanta, Georgia, Estados Unidos, 30308
        • Grady Health System, IDP
    • Mississippi
      • Jackson, Mississippi, Estados Unidos, 39216
        • University of Mississippi
      • Jackson, Mississippi, Estados Unidos, 39213
        • Pediatric Infectious Disease Clinic
      • Jackson, Mississippi, Estados Unidos, 39216
        • Batson Specialty Clinic
    • Ohio
      • Cincinnati, Ohio, Estados Unidos, 45206
        • Cincinnati Center for Clinical Research
    • Texas
      • Dallas, Texas, Estados Unidos, 75235
        • Children's Medical Center of Dallas
      • Houston, Texas, Estados Unidos, 77030
        • Children's Memorial Hermann Hospital
      • Houston, Texas, Estados Unidos, 77030
        • UT Physician
    • Virginia
      • Richmond, Virginia, Estados Unidos, 23298
        • Virginia Commonwealth University
      • Richmond, Virginia, Estados Unidos, 23298
        • VCU Health System Clinical Research Services
  • Italia
      • Padova, Italia, 35128
        • Clinica Pediatrica Azienda Ospedaliera di Padova
      • Padova, Italia, 35128
        • Farmacia Interna
      • Roma, Italia, 00165
        • IRCCS Ospedale Pediatrico Bambino Gesù
      • Torino, Italia, 10126
        • Struttura Complessa a Direzione Universitaria Immunologia, Reumatologia e Malattie Infettive
  • México
    • DF
      • Mexico, DF, México, 06720
        • Hospital Infantil de Mexico Federico Gomez
  • Portugal
      • Faro, Portugal, 8000-386
        • Centro Hospitalar Universitario do Algarve, EPE
      • Lisboa, Portugal, 1169-045
        • Centro Hospitalar de Lisboa Central, EPE
      • Lisboa, Portugal, 1649-035
        • Centro Hospitalar de Lisboa Norte, EPE
      • Porto, Portugal, 4202-451
        • Hospital S. João, E.P.E
  • Puerto Rico
      • San Juan, Puerto Rico, 00935
        • Hospital San Juan Research Unit
  • Sudáfrica
      • Pretoria, Sudáfrica, 0083
        • Embassy Drive Medical Center
    • FREE State
      • Bloemfontein, FREE State, Sudáfrica, 9301
        • IATROS International
    • Gauteng
      • Benoni, Gauteng, Sudáfrica, 1501
        • Lakeview Hospital
      • Ga-Rankuwa, Gauteng, Sudáfrica, 0208
        • Dr George Mukhari Hospital
    • Kwazulu-natal
      • Dundee, Kwazulu-natal, Sudáfrica, 3000
        • Dr. Jan Fourie Medical Centre
  • Tailandia
      • Bangkok, Tailandia, 10330
        • The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT),
      • Bangkok, Tailandia, 10700
        • Department of Pediatrics, Faculty of Medicine, Siriraj Hospital
    • Chiang MAI
      • Muang, Chiang MAI, Tailandia, 50200
        • Department of Pediatrics, Faculty of Medicine, Chiang Mai University
    • Khon Kaen
      • Muang, Khon Kaen, Tailandia, 40002
        • Department of Pediatric, Faculty of Medicine, Khon Kaen University

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

2 años a 18 años (Niño, Adulto)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

Inclusion Criteria:

  • Subjects who are 2-18 years of age, treatment experienced for 6 months or longer with at least 2 ARV drug classes, with HIV-1 RNA ≥1,000 copies/mL

Exclusion Criteria:

  • X4- or dual/mixed-tropic virus detected by the Trofile™ viral tropism assay
  • Concomitant therapy with other investigational agents (other than experimental ARV agents available through pre-approval access programs)
  • Known ≥Grade 3 of any of the following laboratory tests at Screening or within 30 days prior to Baseline Visit: Neutrophil count, hemoglobin, platelets, AST, ALT, and creatinine, lipase;
  • Total bilirubin ≥Grade 3, unless ALL of the following are true: Current regimen includes atazanavir; ALT/AST < 2.5 X ULN; No symptoms other than jaundice or icterus.
  • Other laboratory values ≥Grade 3, must be reviewed by Pfizer.

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
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: Maraviroc

Subjects will be stratified by age and formulation into one of the following cohorts:

Cohort 1: ≥2-<6 years of age, maraviroc liquid formulation; Cohort 2: ≥6-<12 years of age, maraviroc tablet formulation; Cohort 3: ≥6-<12 years of age, maraviroc liquid formulation and Cohort 4: ≥12-<18 years of age, maraviroc tablet formulation.
Droga: Maraviroc
Maraviroc will be administered twice daily either as a liquid or tablet formulation, depending on the age of the subject. The dosage administered will be dependent upon the subject's body surface area as well as the background therapy.
Otros nombres:
  • Selzentría

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Pharmacokinetic(PK): Maraviroc PK Parameter, Average Plasma Concentration (Cavg), Trough Concentration(Cmin), Maximum Plasma Concentration (Cmax)
Periodo de tiempo: Week 2 and Week 48 (0, 1, 2, 4, 6, 8, 12 hours post-dose)
Cavg: calculated as area under the curve divided by a dosing interval of 12 hours. Cmin: directly observed plasma concentration prior to the next dose. Geometric Coefficient of Variation is defined as the geometric standard deviation to the power of the reciprocal of the geometric mean.
Week 2 and Week 48 (0, 1, 2, 4, 6, 8, 12 hours post-dose)
Area Under the Curve at Steady State (AUCtau)
Periodo de tiempo: Week 2 and Week 48 (0, 1, 2, 4, 6, 8, 12 hours post-dose)
AUCtau is the area under the plasma concentration time curve (AUC) at steady state from time zero (pre-dose) to end of dosing interval (tau), here dosing interval is 12 hours.
Week 2 and Week 48 (0, 1, 2, 4, 6, 8, 12 hours post-dose)
Time to Reach Maximum Plasma Concentration (Tmax)
Periodo de tiempo: Week 2 and Week 48 (0, 1, 2, 4, 6, 8, 12 hours post-dose)
Week 2 and Week 48 (0, 1, 2, 4, 6, 8, 12 hours post-dose)
Incidence and Severity of Grade 3 and Grade 4 Treatment-Emergent Adverse Events(AEs) (All Causality)
Periodo de tiempo: Baseline up to 5 years
Incidence is reported in terms of number of events of AEs. The investigator used the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric AEs as follows: Grade 1= Symptoms causing no or minimal interference with usual social and functional activities; Grade 2= Symptoms causing greater than minimal interference with usual social and functional activities; Grade 3= Symptoms causing inability to perform usual social and functional activities; Grade 4= Symptoms causing inability to perform basic self-care functions or medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death. Data have been reported in the measure for Grade 3 and 4 as per system organ class and preferred term.
Baseline up to 5 years
Treatment Discontinuation: Secondary Reasons- Serious Adverse Event (SAE) Related to Study Drug
Periodo de tiempo: Baseline up to 5 years
The primary reason for a participant discontinuing from study drug or the clinical study was recorded in the source documents as well as the case report form. A discontinuation had to be reported immediately to the study medical monitor or his/her designated representative if it was due to an SAE and was considered as a secondary reason.
Baseline up to 5 years

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Percentage of Participants With HIV-1 RNA <400 Copies/mL Through Week 48 Using Missing, Discontinuation = Failure (MD=F) Approach
Periodo de tiempo: Week 24 and Week 48 post-treatment
The proportion of participants who achieved HIV-1 RNA <400 copies/mL at week 24 or 48 was assessed according to Food and Drug Administration's (FDA's) Missing, Switch, Discontinuation'=Failure (MSDF) Snapshot algorithm. The algorithm uses the plasma HIV-1 RNA in the Week 24 or 48 visit window, follows the "virology-first principle" and considers a participant who has a missing plasma HIV-1 RNA, or switches to prohibited ARV regimen or discontinues from the study or study drug for any reason, or dies, as a failure.
Week 24 and Week 48 post-treatment
Percentage of Participants With HIV-1 RNA <48 Copies/mL Through Week 48 Using Missing, Discontinuation = Failure (MD=F)Approach
Periodo de tiempo: Week 24 and Week 48 post-treatment
The proportion of participants who achieved HIV-1 RNA <48 copies/mL at week 24 or 48 was assessed according to Food and Drug Administration's (FDA's) Missing, Switch, Discontinuation'=Failure (MSDF) Snapshot algorithm. The algorithm uses the plasma HIV-1 RNA in the Week 24 or 48 visit window, follows the "virology-first principle" and considers a participant who has a missing plasma HIV-1 RNA, or switches to prohibited ARV regimen or discontinues from the study or study drug for any reason, or dies, as a failure.
Week 24 and Week 48 post-treatment
Percentage of Participants With HIV-1 RNA Levels <400 Copies/mL at Weeks 24 and 48 Using Missing, Discontinuation = Failure (MD=F)Approach
Periodo de tiempo: Week 24 and Week 48 post-treatment
Participants who have been discontinued from the study, have been lost to follow-up, or have missing HIV-1 RNA data prior to the time point of interest were considered to have HIV-1 RNA levels > lower limit of quantification (LLOQ) . This referred to as [non-completer = failure; NC=F] or [missing, discontinuation = failure; MD=F].
Week 24 and Week 48 post-treatment
Percentage of Participants With HIV-1 RNA Levels < 48 Copies/mL at Weeks 24 and 48 Using MD=F Approach
Periodo de tiempo: Week 24 and Week 48 post-treatment
Participants who have been discontinued from the study, have been lost to follow-up, or have missing HIV-1 RNA data prior to the time point of interest were considered to have HIV-1 RNA levels > lower limit of quantification (LLOQ) . This referred as [non-completer = failure; NC=F] or [missing, discontinuation = failure; MD=F].
Week 24 and Week 48 post-treatment
Percentage of Participants With HIV-1 RNA <400 Copies/mL and <48 Copies/mL Using the Time to Loss of Virologic Response Algorithm (TLOVR) at Week 48
Periodo de tiempo: Week 48
TLOVR is defined as the time from first dose of study medication (Day 1) until the time of virologic failure using the a TLOVR algorithm.
Week 48
Percentage of Participants With >= 1.0 log10 Reduction in HIV-1RNA Concentration From Baseline to Week 24 and Week 48
Periodo de tiempo: Baseline to Week 24, Week 48 post-treatment
Percentage of participants with at least a 1.0 log10 reduction in HIV-1 RNA from baseline to Week 24 and Week 48 were tabulated.
Baseline to Week 24, Week 48 post-treatment
Change From Baseline in HIV-1 RNA (Original)
Periodo de tiempo: Baseline, Week 24, Week 48 post-treatment
Plasma HIV-1 RNA was determined using the Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 Test (lower limit of quantification [LLOQ] <48 copies/mL). Blood samples were taken at the time points indicated in the participant evaluation schedule. Screening HIV-1 RNA >1000 copies/ml was used to determine eligibility for the study.
Baseline, Week 24, Week 48 post-treatment
Change From Baseline in HIV-1 RNA (Log10 Copies/mL)
Periodo de tiempo: Baseline, Week 24, Week 48 post-treatment
Plasma HIV-1 RNA was determined using the Roche COBAS AmpliPrep/COBAS TaqMan HIV-1 Test (lower limit of quantification [LLOQ] <48 copies/mL). Blood samples were taken at the time points indicated in the participant evaluation schedule. Screening HIV-1 RNA >1000 copies/ml was used to determine eligibility for the study.
Baseline, Week 24, Week 48 post-treatment
Change From Baseline in Cluster of Differentiation 4 (CD4+) Cell Count at Weeks 24 and 48
Periodo de tiempo: Baseline, Week 24, Week 48 post-treatment
Change from baseline in CD4 cell count to Week 24 and Week 48 were tabulated in aggregated and broken down by age cohort using summary statistics.
Baseline, Week 24, Week 48 post-treatment
Change From Baseline in Percentage (%) of CD4+ Cells at Weeks 24 and 48
Periodo de tiempo: Baseline, Week 24 and Week 48 post-treatment
Change from baseline in CD4 % to Week 24 and Week 48 were tabulated in aggregated and broken down by age cohort using summary statistics.
Baseline, Week 24 and Week 48 post-treatment
Number of Participants With Protocol Defined Virologic Failure
Periodo de tiempo: Week 48
The occurrence of any one of the following criteria would constitute Virologic failure: Criteria A=Decrease from Baseline plasma HIV-1 RNA <1 log10 and plasma HIV-1 RNA >400 copies/mL starting at Week 12 and confirmed at consecutive Week 16; Criteria B=Decrease from Baseline plasma HIV-1 RNA <2.0 log10 and plasma HIV-1 RNA >400 copies/mL at Week 24 OR plasma HIV-1 RNA >10,000 copies/mL on and after Week 24, and confirmed within 14 to 21 days; Criteria C=Increase from nadir plasma HIV-1 RNA of >=1 log10 (>=1,000 copies/mL if nadir plasma HIV-1 RNA <48 copies/mL) at any time, and confirmed within 14 to 21 days.
Week 48
Number of Participants With Viral Tropism Between Screening and Confirmed Protocol Defined Virologic Failure (PDVF) Prior to Week 48
Periodo de tiempo: Screening to Week 48
Virus tropism was determined using the Monogram Biosciences Trofile™ viral tropism assay. Change in detected tropism from screening to the time of failure prior to Week 48 was reported. X4=CXCR4 tropic virus; R5=CCR5-tropic virus; X4=CXCR4-tropic virus. Number of participants as per tropism to respective virus has been reported.
Screening to Week 48
Number of Participants With Emergence of Reverse Transcriptase Inhibitor (RTI) and Protease Inhibitor (PI) Resistance Associated Mutations (RAMs) Between Screening and On-Treatment Confirmed PDVF
Periodo de tiempo: 48 weeks
Phenotypic and genotypic susceptibility to reverse transcriptase and protease inhibitors was evaluated at screening using the Monogram Biosciences PhenoSense™ GT (PSGT) assay. Samples from a confirmatory PDVF visit or early termination of MVC were planned to be analyzed if the plasma HIV-1 RNA was ≥400 copies/mL. Data for participants with respective gene mutation category has been reported. Participants with more than one mutation are counted more than once.
48 weeks
Percentage of Participants With Optimized Background Treatment Susceptibility Scores
Periodo de tiempo: 48 weeks
Data was summarized by the total ARV activity of the background regimen using simple and weighted total optimized background treatment susceptibility scores as well as by screening genotype. Simple total optimized background treatment (OBT) susceptibility scores were categorized as 0, 1, >=2 and weighted total OBT susceptibility scores were categorized as 0 to 0.5, 1 to 1.5 and >=2. However, net susceptibility scores were imputed for simple analysis based on genotype. Susceptibility scores indicate the level resistance to the study medication. Scores ranged from 0 to 1 as 1 = susceptible and potential low-level resistance; 0.5 = low and intermediate-level resistance; 0 = high-level resistance, where higher scores indicated lower resistance.
48 weeks

Colaboradores e Investigadores

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

Patrocinador

ViiV Healthcare

Colaboradores

Pfizer

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.

Enlaces Útiles

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 (Actual)

22 de abril de 2009

Finalización primaria (Actual)

14 de abril de 2015

Finalización del estudio (Anticipado)

30 de junio de 2023

Fechas de registro del estudio

Enviado por primera vez

12 de noviembre de 2008

Primero enviado que cumplió con los criterios de control de calidad

12 de noviembre de 2008

Publicado por primera vez (Estimar)

14 de noviembre de 2008

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

28 de abril de 2020

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

17 de abril de 2020

Última verificación

1 de abril de 2020

Más información

Términos relacionados con este estudio

Palabras clave

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • A4001031
  • 2008-006873-33 (Número EudraCT)

Plan de datos de participantes individuales (IPD)

¿Planea compartir datos de participantes individuales (IPD)?

SÍ

Descripción del plan IPD

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Información sobre medicamentos y dispositivos, documentos del estudio

Estudia un producto farmacéutico regulado por la FDA de EE. UU.

Sí

Estudia un producto de dispositivo regulado por la FDA de EE. UU.

No

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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