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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

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ClinicalTrials.gov Identifier: NCT00791700
Recruitment Status : Active, not recruiting
First Posted : November 14, 2008
Results First Posted : February 25, 2016
Last Update Posted : April 28, 2020
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
ViiV Healthcare

Tracking Information
First Submitted Date  ICMJE November 12, 2008
First Posted Date  ICMJE November 14, 2008
Results First Submitted Date  ICMJE October 6, 2015
Results First Posted Date  ICMJE February 25, 2016
Last Update Posted Date April 28, 2020
Actual Study Start Date  ICMJE April 22, 2009
Actual Primary Completion Date April 14, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 17, 2020)
  • Pharmacokinetic(PK): Maraviroc PK Parameter, Average Plasma Concentration (Cavg), Trough Concentration(Cmin), Maximum Plasma Concentration (Cmax) [ Time Frame: 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.
  • Area Under the Curve at Steady State (AUCtau) [ Time Frame: 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.
  • Time to Reach Maximum Plasma Concentration (Tmax) [ Time Frame: 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) [ Time Frame: 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.
  • Treatment Discontinuation: Secondary Reasons- Serious Adverse Event (SAE) Related to Study Drug [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: November 12, 2008)
  • To determine the safety and tolerability of maraviroc in HIV-infected children and adolescents. [ Time Frame: 48 weeks ]
  • To determine the pharmacokinetic profile(s) and dosing schedule(s) for maraviroc in treatment experienced HIV-infected children and adolescents on different background therapies; [ Time Frame: 48 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 17, 2020)
  • Percentage of Participants With HIV-1 RNA <400 Copies/mL Through Week 48 Using Missing, Discontinuation = Failure (MD=F) Approach [ Time Frame: 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.
  • Percentage of Participants With HIV-1 RNA <48 Copies/mL Through Week 48 Using Missing, Discontinuation = Failure (MD=F)Approach [ Time Frame: 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.
  • Percentage of Participants With HIV-1 RNA Levels <400 Copies/mL at Weeks 24 and 48 Using Missing, Discontinuation = Failure (MD=F)Approach [ Time Frame: 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].
  • Percentage of Participants With HIV-1 RNA Levels < 48 Copies/mL at Weeks 24 and 48 Using MD=F Approach [ Time Frame: 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].
  • 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 [ Time Frame: 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.
  • Percentage of Participants With >= 1.0 log10 Reduction in HIV-1RNA Concentration From Baseline to Week 24 and Week 48 [ Time Frame: 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.
  • Change From Baseline in HIV-1 RNA (Original) [ Time Frame: 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.
  • Change From Baseline in HIV-1 RNA (Log10 Copies/mL) [ Time Frame: 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.
  • Change From Baseline in Cluster of Differentiation 4 (CD4+) Cell Count at Weeks 24 and 48 [ Time Frame: 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.
  • Change From Baseline in Percentage (%) of CD4+ Cells at Weeks 24 and 48 [ Time Frame: 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.
  • Number of Participants With Protocol Defined Virologic Failure [ Time Frame: 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.
  • Number of Participants With Viral Tropism Between Screening and Confirmed Protocol Defined Virologic Failure (PDVF) Prior to Week 48 [ Time Frame: 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.
  • 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 [ Time Frame: 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.
  • Percentage of Participants With Optimized Background Treatment Susceptibility Scores [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 12, 2008)
  • Describe the efficacy of multiple dose administration of maraviroc in treatment experienced children infected with CCR5 tropic HIV-1; [ Time Frame: 48 weeks ]
  • Describe tropism changes over time. [ Time Frame: 48 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Human Immunodeficiency Virus
Intervention  ICMJE Drug: 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.
Other Name: Selzentry
Study Arms  ICMJE 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.

Intervention: Drug: Maraviroc
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: January 28, 2016)
103
Original Estimated Enrollment  ICMJE
 (submitted: November 12, 2008)
125
Estimated Study Completion Date  ICMJE June 30, 2023
Actual Primary Completion Date April 14, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Years to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Brazil,   Italy,   Mexico,   Portugal,   Puerto Rico,   South Africa,   Spain,   Thailand,   United States
Removed Location Countries France,   Tanzania
 
Administrative Information
NCT Number  ICMJE NCT00791700
Other Study ID Numbers  ICMJE A4001031
2008-006873-33 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: 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.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Responsible Party ViiV Healthcare
Study Sponsor  ICMJE ViiV Healthcare
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account ViiV Healthcare
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP