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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. dubna 2020 aktualizováno: 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.

Přehled studie

Postavení

Aktivní, ne nábor

Podmínky

Intervence / Léčba

Typ studie

Intervenční

Zápis (Aktuální)

103

Fáze

  • Fáze 2

Kontakty a umístění

Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.

Studijní místa

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

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

2 roky až 18 let (Dítě, Dospělý)

Přijímá zdravé dobrovolníky

Ne

Pohlaví způsobilá ke studiu

Všechno

Popis

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.

Studijní plán

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

  • Primární účel: Léčba
  • Intervenční model: Paralelní přiřazení
  • Maskování: Žádné (otevřený štítek)

Zbraně a zásahy

Skupina účastníků / Arm
Intervence / Léčba
Experimentální: 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.
Lék: 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.
Ostatní jména:
  • Selzentry

Co je měření studie?

Primární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Pharmacokinetic(PK): Maraviroc PK Parameter, Average Plasma Concentration (Cavg), Trough Concentration(Cmin), Maximum Plasma Concentration (Cmax)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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)
Časové okno: 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
Časové okno: 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

Sekundární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Percentage of Participants With HIV-1 RNA <400 Copies/mL Through Week 48 Using Missing, Discontinuation = Failure (MD=F) Approach
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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)
Časové okno: 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)
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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
Časové okno: 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

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

ViiV Healthcare

Spolupracovníci

Pfizer

Publikace a užitečné odkazy

Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.

Užitečné odkazy

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia (Aktuální)

22. dubna 2009

Primární dokončení (Aktuální)

14. dubna 2015

Dokončení studie (Očekávaný)

30. června 2023

Termíny zápisu do studia

První předloženo

12. listopadu 2008

První předloženo, které splnilo kritéria kontroly kvality

12. listopadu 2008

První zveřejněno (Odhad)

14. listopadu 2008

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Aktuální)

28. dubna 2020

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

17. dubna 2020

Naposledy ověřeno

1. dubna 2020

Více informací

Termíny související s touto studií

Klíčová slova

Další relevantní podmínky MeSH

Další identifikační čísla studie

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

Plán pro data jednotlivých účastníků (IPD)

Plánujete sdílet data jednotlivých účastníků (IPD)?

ANO

Popis plánu 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.

Informace o lécích a zařízeních, studijní dokumenty

Studuje lékový produkt regulovaný americkým FDA

Ano

Studuje produkt zařízení regulovaný americkým úřadem FDA

Ne

Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .

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Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

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Podmínky

Vzácné nemoci

Drogové intervence

Doplňky stravy

Sponzor / Spolupracovníci

Místa

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