Trial record 1 of 1 for:
An open label pharmacokinetic, safety and efficacy study of maraviroc in combination
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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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 |
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Recruitment Status :
Active, not recruiting
First Posted : November 14, 2008
Results First Posted : February 25, 2016
Last Update Posted : September 12, 2019
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Sponsor:
ViiV Healthcare
Collaborator:
Pfizer
Information provided by (Responsible Party):
ViiV Healthcare
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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 |
| 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 |
|---|---|
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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 :
- Pharmacokinetic (PK) Parameters for Participants With Data in Stage 1 Enrolled in Stage 2 - Week 48 [ Time Frame: Week 2 and Week 48 (0, 1, 2, 4, 6, 8, 12 hours post-dose) ]A PK analysis was performed using PK data from participants that participated in Stage 1 (PK Populations 2 and 3) where intensive maraviroc (MVC) PK data were available at Week 2. The primary aim of this analysis was to describe and summarize MVC PK parameters at Week 2 and Week 48 by cohort and Optimized Background Treatment (OBT) group. Geometric Coefficient of Variation is defined as the geometric standard deviation to the power of the reciprocal of the geometric mean.
- PK Parameters for Stage 1 Participants Enrolled in Stage 2 - Week 2 Results for Stage 2 Doses - AUCtau (Area Under the Curve at Steady State) [ Time Frame: Week 2 and Week 48 (0, 1, 2, 4, 6, 8, 12 hours post-dose) ]A PK analysis was performed using PK data from participants that participated in Stage 1 (PK Populations 2 and 3) where intensive maraviroc (MVC) PK data were available at Week 2. The primary aim of this analysis was to describe and summarize MVC PK parameters (AUCtau) at Week 2 and Week 48 by cohort and Optimized Background Treatment (OBT) group. Correlations between MVC PK and efficacy as well as compliance were also assessed.
- PK Parameters for Stage 1 Participants Enrolled in Stage 2 - Week 2 Results for Stage 2 Doses - Tmax (Time at Maximum Concentration) [ Time Frame: Week 2 and Week 48 (0, 1, 2, 4, 6, 8, 12 hours post-dose) ]A PK analysis was performed using PK data from participants that participated in Stage 1 (PK Populations 2 and 3) where intensive maraviroc (MVC) PK data were available at Week 2. The primary aim of this analysis was to describe and summarize MVC PK parameters (Tmax) at Week 2 and Week 48 by cohort and Optimized Background Treatment (OBT) group. Correlations between MVC PK and efficacy as well as compliance were also assessed.
- Incidence and Severity of Grade 3 and Grade 4 Treatment-Emergent Adverse Events (All Causality) [ Time Frame: 48 weeks ]Safety was assessed by spontaneous reports, physical examination and laboratory test results in all participants who received at least 1 dose of study drug. The investigator used the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric AEs.
- Treatment Discontinuation Secondary to Serious Adverse Event (SAE) Related to Study Drug [ Time Frame: Week 48 ]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.
Secondary Outcome Measures :
- Percentage of Participants With HIV‑1 RNA <400 Copies/mL Through Week 48 (MSDF) [ 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. The percentage of participants is reported below.
- Percentage of Participants With HIV‑1 RNA <48 Copies/mL Through Week 48 (MSDF) [ 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. The percentage of participants is reported below.
- 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 will be referred to as [non-completer = failure; NC=F] or [missing, discontinuation = failure; MD=F]. The proportion of participants (100*n/N) is reported below.
- 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 will be referred to as [non-completer = failure; NC=F] or [missing, discontinuation = failure; MD=F]. The proportion of participants (100*n/N) is reported below. The proportion of participants (100*n/N) is reported below.
- 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: Week 24 and Week 48 post-treatment ]Percentage of subjects with at least a 1.0 log10 reduction in HIV-1 RNA from baseline to Week 24 and Week 48 were tabulated.
- Summary of Change From Baseline in HIV-1 RNA (Original) by Visit [ Time Frame: Week 24 and 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.
- Summary of Change From Baseline in HIV-1 RNA (Log10 Copies/mL) by Visit [ Time Frame: Week 24 and 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: Week 24 and 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 CD4+ Percent (%) at Weeks 24 and 48 [ Time Frame: 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.
- Protocol Defined Virologic Failure [ Time Frame: Week 48 ]
The occurrence of any one of the following criteria would constitute Virologic failure:
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; 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; 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.
- Shift Table of Viral Tropism Between Screening and Confirmed PDVF Prior to Week 48 [ Time Frame: Screening and Week 48 ]Virus tropism was determined using the Monogram Biosciences Trofile™ viral tropism assay. A shift table of the change in detected tropism from screening to the time of failure was produced in the aggregate and also broken down by age cohort.
- Summary of the Emergence of Reverse Transcriptase Inhibitor (RTI) and Protease Inhibitor (PI) Resistance Associated Mutations (RAMs) Between Screening and On-Treatment Confirmed PDVF: Total and by Cohort Prior to Week 48 [ 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. Participants with more than one mutation are counted more than once.
- Optimized Background Treatment (OBT) Susceptibility Scores (Net/Overall) by Outcome [ Time Frame: 48 weeks ]Outcome (Response, PDVF or other/remainder) was summarized by the total ARV activity of the background regimen using simple and weighted totals (TOBT and p-wTOBTss, respectively) in the aggregate, categorized as 0, 1, ≥2 (TOBT) and 0 0.5, 1 1.5 and ≥2 (p-wOBTss) respectively, as well as by screening genotype. Six participants (Response: n=5; Other failure: n=1) failed to have successful PhenoSense GT analysis at screening, and so a net susceptibility score was not generated. One more participant was not included in the wOBTss analysis due to failed phenotype analysis. However, net susceptibility scores were imputed for simple analysis based on genotype. Susceptibility scores indicate the level resistance to the study medication. Scores include: 1 = susceptible and potential low-level resistance; 0.5 = low and intermediate-level resistance; 0 = high-level resistance.
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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 41 study locations
Sponsors and Collaborators
ViiV Healthcare
Pfizer
Investigators
| Study Director: | Pfizer CT.gov Call Center | Pfizer |
Additional Information:
| 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: | September 12, 2019 |
| Last Verified: | September 2019 |
| 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 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by ViiV Healthcare:
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Open label pharmacokinetic safety and efficacy in HIV-1 infected pediatrics |
Additional relevant MeSH terms:
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Maraviroc 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 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 |