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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

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.

Condition or disease Intervention/treatment Phase
Human Immunodeficiency Virus Drug: Maraviroc Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 103 participants
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : April 22, 2009
Actual Primary Completion Date : April 14, 2015
Estimated Study Completion Date : June 30, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
Drug Information available for: Maraviroc

Arm Intervention/treatment
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.

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




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. Time to Reach Maximum Plasma Concentration (Tmax) [ Time Frame: Week 2 and Week 48 (0, 1, 2, 4, 6, 8, 12 hours post-dose) ]
  4. 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.

  5. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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].

  4. 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].

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   2 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00791700


Locations
Show Show 41 study locations
Sponsors and Collaborators
ViiV Healthcare
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
Additional Information:
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Responsible Party: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT00791700    
Other Study ID Numbers: A4001031
2008-006873-33 ( EudraCT Number )
First Posted: November 14, 2008    Key Record Dates
Results First Posted: February 25, 2016
Last Update Posted: April 28, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by ViiV Healthcare:
Open label pharmacokinetic safety and efficacy in HIV-1 infected pediatrics
Additional relevant MeSH terms:
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Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Maraviroc
HIV Fusion Inhibitors
Viral Fusion Protein Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
CCR5 Receptor Antagonists